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News Capsules - May 2025

Long-Term Effects of Atorvastatin in Cardiovascular Disease

The Anglo-Scandinavian Cardiac Outcomes Trial investigated the long-term effects of atorvastatin, a cholesterol-lowering drug, on cardiovascular (CV) disease in hypertensive individuals with additional risk factors. The lipid-lowering arm of the trial randomized over 10,000 participants with total cholesterol <6.5 mmol/L to receive either atorvastatin 10 mg or a placebo for an average of 3.3 years. The initial results showed that atorvastatin significantly reduced the incidence of major CV events like myocardial infarction (MI) and stroke.

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Brexpiprazole for Adolescents with Schizophrenia

A randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy and safety of brexpiprazole in adolescents (ages 13 to 17) with schizophrenia. Participants in the trial had a confirmed diagnosis of schizophrenia, a history of illness for at least 6 months, a need for antipsychotic medication, and a score of 80 or greater on the Positive and Negative Syndrome Scale (PANSS).

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Cenobamate in Drug-Resistant Epilepsy

A retrospective, multicenter study analyzed the real-world effectiveness and tolerability of cenobamate as adjunctive therapy for adults with drug-resistant focal-onset seizures participating in Early Access Programs. The study included 298 patients with a long history of epilepsy (median 22 years) and a high number of previously failed antiseizure medications, with 41.9% having undergone epilepsy surgery. The primary efficacy endpoint was a 50% or greater reduction in seizure frequency after 3 months of maintenance therapy.

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Inebilizumab in Generalized Myasthenia Gravis

Autoimmune myasthenia gravis is characterized by autoreactive B cells producing autoantibodies that disrupt neuromuscular transmission, leading to fluctuating muscle weakness. Current treatments include glucocorticoids, cholinesterase inhibitors, thymectomy, and immunosuppressants, which aim to reduce mortality and alleviate symptoms; however, limitations in efficacy, side effects, and poor response in some patients highlight the need for alternative therapies.

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Drug News Abstracts Archive

Drug News Abstracts - February 2023
Momelotinib a Good Choice for Myelofibrosis with Anemia Treatment with momelotinib resulted in clinically significant improvements in patients with myelofibrosis. Improvements were seen in myelofibrosis-associated symptoms, measures of anemia, and spleen response when compared to the Janus kinase (JAK) inhibitor danazol. Impaired JAK signaling in myelofibrosis drives overproduction of inflammatory cytokines, bone marrow fibrosis, and systemic symptoms, as well as splenomegaly. The resulting chronic inflammation drives hyperactivation of the protein activin A receptor, type 1 (ACVR1) and elevated hepcidin, dysregulated iron metabolism, and anemia. JAK inhibitors disrupt this pathway, reducing spleen size and the symptom burden of myelofibrosis. Momelotinib, a first-in-class inhibitor, not just of JAK1 and JAK2, but also of ACVR1, also disrupts the hepcidin pathway, improving anemia over time.READ MORE...MOMENTUM is an ongoing double-blind, randomized phase 3 study of momelotinib vs. danazol in symptomatic, anemic patients who had already received treatment with JAK inhibitors. The study enrolled 195 patients at 107 sites across 21 countries; patients were at least 18 years old, had confirmed diagnosis of primary myelofibrosis, post-polycythemia vera, or post-essential thrombocytopenia myelofibrosis. Patients were randomly assigned to receive 200 mg momelotinib PO once daily plus placebo or 300 mg danazol PO twice daily plus placebo; 130 patients were assigned to the momelotinib group and 65 patients to the danazol group. MOMENTUM was conducted from April 2020 to December 2021, with a 24-week treatment period. The study was blinded for those 24 weeks, and then patients could enter an open-label crossover phase, during which they received 200 mg/day momelotinib.The study examined the total symptom score (TSS) response rate on the Myelofibrosis Symptom Assessment Form at week 24. Response was defined as a 50% or greater reduction in mean TSS, compared with baseline. A significantly greater proportion of patients in the momelotinib group reported such response than in the danazol group: 25% (32/130) vs. 9% (6/65). The week 24 symptom response was sustained through week 48 in almost all patients, and new responders were observed at week 48 among those who were nonresponders at week 24: 12/61 in the momelotinib arm and 10/35 in the danazol arm.Approximately half of the patients were transfusion-dependent at baseline (that is, needing 4 units or more of red cell or whole blood transfused in the 8 weeks before study initiation), with an additional 35% requiring some transfusion support. Week 24 transfusion independence (TI) response was seen in 31% in the momelotinib group and in 20% in the danazol group. TI responses at week 24 were also sustained through week 48 in 90% of patients who had initiated treatment with momelotinib and in 77% of those who had initiated treatment with danazol before the crossover phase. (Verstovsek, S., et al. (2023). Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): Results from an international, double-blind, randomized, controlled, phase 3 study. Lancet, 401 (10373): 269–280. Retrieved February 2023 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02036-0/fulltext; Gerds, A. (2023 ). Updated results from the MOMENTUM phase 3 study of momelotinib (MMB) vs. danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor . OncLive. [Video]. Retrieved February 2023 from https://www.onclive.com/view/updated-results-from-the-momentum-phase-3-study-of-momelotinib-mmb-versus-danazol-dan-in-symptomatic-and-anemic-myelofibrosis-mf-patients-previously-treated-with-a-jak-inhibitor)Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer Novel Oral Poliovirus Vaccine Type 2 and Newborns A phase 2, randomized, double-blind, controlled trial published in  The Lancet  offers data that novel oral poliovirus vaccine type 2 (nOPV2), which has previously been studied in populations who have already been vaccinated against polio, was safe and immunogenic in newborns who had not received any other poliovirus vaccine.READ MORE...The leading cause of poliomyelitis currently is type 2 circulating vaccine-derived poliovirus (CVDPV2) from Sabin oral poliovirus vaccines (OPVs). Attenuated polioviruses can mutate, and the mutation can result in vaccine-associated polio in vaccine recipients and susceptible close contacts; in settings where immunization coverage is poor, this can lead to the emergence of CVDPVs. To mitigate these risks, the nOPV2 has been developed to be more genetically stable, reducing the risk of CVDPV2, to which unvaccinated newborns are especially vulnerable.The study randomized 330 infants from a single health research center in Bangladesh to receive either two doses of nOPV2 (n = 220) or placebo (n = 110), administered at age 0 to 3 days and at age 4 weeks. The two study groups were similar in sex as well as birth weight and birth length of the infants. Infants were excluded from the study for previous receipt of poliovirus or rotavirus vaccine, infection or illness at the time of enrollment, suspicion of immunodeficiency in the infant or a close family member, or contraindication to venipuncture.Poliovirus neutralizing antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. At birth, nearly all infants (93%) had seroprotective maternal antibodies against type 2 polioviruses; by week 8, only 56% of the placebo group still retained these maternal antibodies. Of the 16 infants in the nOPV2 group who were initially unprotected at birth, with no detectable titers, 8 had seroprotective titers by week 4 and all had seroprotective antibodies by week 8.The vaccine was as well tolerated as placebo, causing only mild or moderate adverse events: 154 (70%) in the nOPV2 group and 78 (71%) in the placebo group. No immediate reactions were seen within 30 minutes of vaccination. The most frequent solicited events were instability, abnormal crying, and poor feeding. Severe unsolicited events were reported in 11 (5%) vaccine recipients and in 5 (5%) placebo recipients, most commonly pneumonia.More than 450 million doses of this vaccine have already been distributed to control CVDPV2 outbreaks, and it has been important to determine safety in young infants, as they are among those at highest risk in these outbreaks. The study found no detectable shedding of poliovirus in baseline stool samples; 2 weeks after the first vaccine dose, type 2 viral shedding was detectable in 52% of recipients; 2 weeks after the second vaccine, viral shedding had increased to 64%, before gradually decreasing to nearly 0 by week 12. These data are helpful for health care administrators and others responsible for implementing such vaccination campaigns. (Slomski, A. (2023). Novel oral polio vaccine safety induces antibodies among vaccine-naïve infants.  JAMA, 329 (4), 279. Retrieved February 2023 from https://jamanetwork.com/journals/jama/fullarticle/2800664; Zaman, K. (2023). Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: A randomized, controlled, phase 2 clinical trial.  Lancet, 401 (10371), 131–139. Retrieved February 2023 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02397-2/fulltext)Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer Effectiveness of Outpatient SARS-CoV2 Treatments in Patients with Systemic Autoimmune Rheumatic Disease The risk of severe COVID-19 infection is cause for concern in patients with systemic autoimmune rheumatic disease and immunosuppression. Even in a cohort of these patients who were mostly vaccinated against SARS-CoV2, outpatient treatment substantially reduced odds of severe COVID-19 outcomes compared with no outpatient treatment. These are the findings of a retrospective cohort study conducted in an integrated health care system in Boston. This is one of the first studies to evaluate outpatient SARS-CoV2 treatments among patients with systemic autoimmune rheumatic disease that includes oral outpatient treatment options and quantifies the prevalence of COVID-19 rebound.READ MORE...Researchers identified 704 patients age 18 or older with preexisting systemic autoimmune rheumatic disease who had COVID-19 onset between January and May 2022. Using data from the electronic medical record, researchers identified SARS-CoV2 infection by record of positive PCR or antigen test results, rheumatic disease by diagnosis codes and immunomodulator prescriptions, and outpatient COVID-19 treatment by prescription. If the patient received more than one outpatient COVID treatment, it was classified as combination treatment. Mean age of patients selected was 58.4 years; 76% were female and 84% were white. Of the 704 patients, 347 had rheumatoid arthritis, 113 had psoriatic arthritis, and 87 had systemic lupus erythematosus. The rheumatic disease was treated in 484 patients using conventional DMARDs, most commonly methotrexate (n = 232) and hydroxychloroquine (n = 214); in 258 patients, the rheumatic disease was treated using biologic DMARDs, most frequently tumor necrosis factor inhibitors (n = 144).Use of outpatient treatments for COVID-19 in these patients increased in frequency over the course of the trial: 20/57 (35%) patients in the first week of the study received outpatient treatment, compared with 44/68 (65%) in the last full week of the study. Overall, 61% (426/704) of patients received outpatient treatment:307 patients were treated with oral nirmatrelvir-ritonavir.105 patients were treated with monoclonal antibodies.5 patients were treated with oral molnupiravir.3 patients were treated with remdesivir.6 patients were treated with combination treatments.The primary outcomes in the trial were severe COVID-19, defined as hospitalization or death within 30 days of infection, and COVID-19 rebound, defined as documentation of a negative SARS-CoV2 test after treatment, followed by a newly positive test. A total of 58 hospitalizations, including 3 deaths, occurred within 30 days of the COVID-19 index date: 9 patients (2.1%) among the 426 patients who received outpatient treatment required hospitalization, compared with 49 patients (17.6%) among the 278 patients who did not. One of the 3 deaths occurred among those who received treatment. Severe outcomes occurred in 4.8% of those whose COVID-19 infection was treated with monoclonal antibodies (n = 5) and in 1.3% of those treated with oral nirmatrelvir-ritonavir (n = 4), with 1 death. No severe COVID-19 occurred in those treated with molnupiravir, remdesivir, or combination treatment. Among the 27 unvaccinated patients, 2 (7.4%) had severe outcomes; neither had received outpatient treatments. Of the 58 patients with severe COVID-19 outcomes on primary analysis, 46 (79%) were considered by independent reviewers to have COVID-19 as the primary or partial reason for hospitalization, with 29 of them having COVID-19 pneumonia. Documented COVID-19 rebound occurred in 7.9% of patients with systemic autoimmune rheumatic disease who received oral outpatient treatment (n = 25/318). The exact mechanisms of COVID-19 rebound are unknown but might reflect incomplete viral eradication at the completion of oral SARS-CoV2 treatment. It’s possible that the underlying immunosuppression in these patients may play a role in the higher risk of COVID-19 rebound.These results should encourage clinicians to prescribe–and patients with these rheumatic diseases to seek–prompt outpatient SARS-CoV2 treatment. (Qianj, G., et al. (2023). Outcomes with and without outpatient SARS-CoV2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: A retrospective cohort study.  Lancet Rheumatol, 5 (3), E139–E150. Retrieved February 2023 from  https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00006-1/fulltext )Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - January 2023
Interim Results Indicate that Emicizumab-kxwh Prevents Bleeding Episodes in Hemophilia AHemophilia A is an inherited disorder in which lack of intrinsic factor VIII leads to frequent bleeding into joints and muscles, resulting in chronic swelling, deformity, reduced mobility, and long-term joint damage. The World Federation of Hemophilia recommends early prophylaxis, but commonly, treatment is not initiated until after the first year of life because of the related high burden of care. The study design aims to address that by offering the parents options of dosage regimen and subcutaneous administration.READ MORE...Genentech released interim data from the HAVEN 7 study at the American Society of Hematology’s annual meeting in New Orleans in December. HAVEN 7 is a Phase III, multicenter, open-label study that evaluated the benefits of preventive treatment with emicizumab-kxwh, a factor IXa- and factor X-directed antibody, in previously untreated severe hemophilia A without factor VIII inhibitors. (A serious complication of treatment for hemophilia A is the development of inhibitors to factor VIII replacement therapies.) Hypothesizing that beginning treatment as early as possible could produce improved results, the study enrolled patients with severe hemophilia A, demonstrated by an intrinsic factor VIII level of less than 1%. The infants could begin treatment as early as birth to age 12 months, and were given emicizumab subcutaneously at 3 mg/kg once every 2 weeks for 52 weeks; after 1 year, parents could opt for their infants to continue with emicizumab treatment in three different dosage regimens: 1 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks.On interim analysis, emicizumab-kxwh achieved meaningful control of bleeding: 77.8% (n = 42) of treated infants had no bleeds that required treatment, and 42.6% (n = 23) had no incidents of bleeding at all. The report showed that a total of 77 bleeds occurred in 31 participants; 88.3% of those bleeds were a result of injury rather than being spontaneous bleeds. No spontaneous bleeds were serious enough to require treatment. The annualized bleeding rate at the time of this analysis was 0.4 for treated bleeds. The safety profile in these younger patients was consistent with the findings in previous studies, with no new safety issues noted and all reported adverse events were local injection-site reactions.These results are quite promising and suggest that treatment of hemophilia A with emicizumab can safely start at birth. Continued monitoring of these infants over the 7 years of follow-up should provide useful long-term data on joint health and safety.(Genentech. (2022, December 10). Interim data from Phase III study presented at ASH 2022 show Hemlibra (emicizumab-kxwh) achieved meaningful bleed control in infants from birth. [Press release]. Retrieved January 2023 fromhttps://www.gene.com/media/press-releases/14975/2022-12-10/interim-data-from-phase-iii-study-presen)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerLSD Therapy Seen as Effective for AnxietyPsychedelics such as LSD [lysergic acid diethylamide] and psilocybin induce profound, acute mood alterations and mystical-type experiences, primarily by interacting with the serotonin 5HT2A receptor. Because of those effects on mood, they have been posited as an alternative treatment option for anxiety. Most research in the therapeutic potential of psychedelics used psilocybin, but a current study investigated the effects of LSD on anxiety, depression, and overall psychiatric symptomatology in patients with anxiety associated with life-threatening illnesses and in those with anxiety without life-threatening illness.READ MORE...The Swiss study, a multicenter, randomized, double-blind, placebo-controlled, crossover design, aimed to corroborate the findings of a small pilot study, in which patients who received LSD demonstrated trends toward reduction in anxiety associated with life-threatening illness. The trial also included patients with psychiatric anxiety disorders in the absence of life-threatening illness. In the crossover design, the patients underwent two 200-µg LSD sessions and two placebo sessions. All patients were intended to receive both LSD and placebo. To be included in the study, patients with life-threatening disorders had to meet the DSM-IV criteria for anxiety disorder or score at least 40 points on the state or trait scales of the Spielberger State-Trait Anxiety Inventory (STAI) at study inclusion. Those without life-threatening illnesses had to meet DSM-IV criteria for at least one anxiety disorder; elevated STAI scores were not sufficient for inclusion.The study involved a screening visit and two 24-week treatment periods per participant. Each treatment period consisted of two treatment sessions and five study visits, with treatment sessions separated by 6 weeks. Study visits occurred at baseline, between treatment sessions, and at 2, 8, and 16 weeks after the second treatment session, with the 16-week visit counting as the end-of-study visit. Results were analyzed for 42 participants, 20 patients who had a life-threatening illness and anxiety and 22 with anxiety disorder not associated with an illness.Use of LSD during two treatment sessions induced rapidand lasting reductions in anxiety, depression, and general psychiatric symptoms for up to 16 weeks. Effects were maximal at the 2-week study visit and were sustained up to 16 weeks. Least-square mean change for baseline in STAI-Global score at 16 weeks was –14.9 in the LSD group and +1.3 in the placebo group, for a significant difference in anxiety reduction. Similar effects were observed for ratings of comorbid depression: the difference on the Hamilton Depression Rating Scale, 21-item was –7.0 and on the Beck Depression Inventory was –6.1. Positive acute subjective drug effects and mystical-type experiences correlated with the long-term reductions in anxiety symptoms. Clinical response (30% or greater reduction in STAI-G scores) was seen in 65% (13/20) in the LSD group and in 9% (2/22) in the placebo group at any outcome visit.Transient, mild adverse effects were reported by 8 patients (19%) and one serious treatment-related adverse event (acute treatment anxiety and delusions) occurred. The serious effect was successfully treated with lorazepam and olanzapine, and the patient then received 100 µg at the second treatment session. In addition, in 3 patients, the dose in the second session was decreased because the response during the first session was considered too strong. The authors strongly recommend the use of two doses, as such a schedule allows the patient to become more familiar with the effects of psychedelics and potentially have better experiences in cases like these, where the first dose was challenging.No real blinding was possible in this study, because of the characteristic effects of LSD; in addition, due to the crossover design, patients who received LSD in the first treatment session had persistent therapeutic effects that continued into the second treatment period whether they received placebo or LSD. Also, both patients and therapists were highly motivated, which might be difficult to replicate in the general population. Larger trials will be needed to confirm these findings. (Holze, F., et al. (2023). Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness: A randomized, double-blind, placebo-controlled phase II study. Biol Psychiatr, 93(3), 215-223. Retrieved January 2023 from https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01553-0/fulltext)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerRituximab for Connective Tissue Disease-Associated Interstitial Lung DiseaseManagement of interstitial lung disease (ILD) associated with connective tissue disease (CTD) has been challenging. International guidelines recommend IV cyclophosphamide for severe or progressive scleroderma-associated ILD, but its use is limited by adverse effects. Rituximab is often used as rescue therapy for treatment-refractory CTD-associated ILD but has not been studied in clinical trials. A report in The Lancet Respiratory Medicine described the findings of the first study to compare these two treatments for CTD-associated ILD.READ MORE...The RECITAL study is a randomized, double-blind, double-placebo, phase 2b trial that compared IV rituximab with IV cyclophosphamide for CTD-ILD, using a design that included a range of CTD diagnoses. Between December 2014 and March 2020, 145 participants were recruited from specialist ILD or rheumatology centers in the UK. Patients ages 18 to 80 (mean age, 56.6 years) with severe or progressive ILD related to scleroderma (n = 37), idiopathic inflammatory myositis (n = 44), or mixed connective tissue disease (n = 16) were randomized to IV rituximab (1,000 mg on day 0 and day 14, with placebo given every 4 weeks from week 4 to week 20; n = 51) or to IV cyclophosphamide (600 mg/m2 BSA every 4 weeks to week 20 with placebo given on day 14; n = 50).Improvement in lung function was measured in changes from baseline in forced vital capacity at 24 weeks; researchers found no significant differences between the two groups: The unadjusted mean increase in forced vital capacity at 24 weeks was 99 mL with cyclophosphamide and 97 mL with rituximab. Improvements were also seen in quality of life scores on various tools: quality of life scores on the St. George’s Respiratory Questionnaire, in which higher scores indicate more respiratory-related limitations, fell by 4.8 points at week 24 in the cyclophosphamide group and by 3.4 points in the rituximab group; on the King’s Brief Interstitial Lung Disease questionnaire, scores improved by 9.4 points in the cyclophosphamide group and by 8.8 points in the rituximab group at 24 weeks. Overall survival, progression-free survival, and time to treatment failure did not differ significantly between groups.Rituximab use was associated with a lower number of adverse events (445 vs. 646 with cyclophosphamide) and with a 13.3% reduction in concomitant corticosteroid use. Cyclophosphamide use has been limited by toxicity (nausea, GI upset, hematuria, and increased risk of gonadal failure and of bladder cancer). This trial offers evidence supporting rituximab use and demonstrating that it may be a safe alternative to cyclophosphamide in CTD-ILD patients. Future studies could examine its use as part of combination treatment for CTD-ILD patients. (Manfredi, A., et al. (2023). Rituximab for connective tissue disease-associated interstitial lung disease. Lancet Respir Med, 11(1), 3-4. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00356-3/fulltext?dgcid=raven_jbs_etoc_email; Maher, T. M., et al. (2023). Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomized, controlled, phase 2b trial. Lancet Respir Med, 11(1), 45-54. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00359-9/fulltext?dgcid=raven_jbs_etoc_feature_lanres#seccestitle10)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerRituximab for Connective Tissue Disease-Associated Interstitial Lung DiseaseManagement of interstitial lung disease (ILD) associated with connective tissue disease (CTD) has been challenging. International guidelines recommend IV cyclophosphamide for severe or progressive scleroderma-associated ILD, but its use is limited by adverse effects. Rituximab is often used as rescue therapy for treatment-refractory CTD-associated ILD but has not been studied in clinical trials. A report in The Lancet Respiratory Medicine described the findings of the first study to compare these two treatments for CTD-associated ILD.The RECITAL study is a randomized, double-blind, double-placebo, phase 2b trial that compared IV rituximab with IV cyclophosphamide for CTD-ILD, using a design that included a range of CTD diagnoses. Between December 2014 and March 2020, 145 participants were recruited from specialist ILD or rheumatology centers in the UK. Patients ages 18 to 80 (mean age, 56.6 years) with severe or progressive ILD related to scleroderma (n = 37), idiopathic inflammatory myositis (n = 44), or mixed connective tissue disease (n = 16) were randomized to IV rituximab (1,000 mg on day 0 and day 14, with placebo given every 4 weeks from week 4 to week 20; n = 51) or to IV cyclophosphamide (600 mg/m2 BSA every 4 weeks to week 20 with placebo given on day 14; n = 50).Improvement in lung function was measured in changes from baseline in forced vital capacity at 24 weeks; researchers found no significant differences between the two groups: The unadjusted mean increase in forced vital capacity at 24 weeks was 99 mL with cyclophosphamide and 97 mL with rituximab. Improvements were also seen in quality of life scores on various tools: quality of life scores on the St. George’s Respiratory Questionnaire, in which higher scores indicate more respiratory-related limitations, fell by 4.8 points at week 24 in the cyclophosphamide group and by 3.4 points in the rituximab group; on the King’s Brief Interstitial Lung Disease questionnaire, scores improved by 9.4 points in the cyclophosphamide group and by 8.8 points in the rituximab group at 24 weeks. Overall survival, progression-free survival, and time to treatment failure did not differ significantly between groups.Rituximab use was associated with a lower number of adverse events (445 vs. 646 with cyclophosphamide) and with a 13.3% reduction in concomitant corticosteroid use. Cyclophosphamide use has been limited by toxicity (nausea, GI upset, hematuria, and increased risk of gonadal failure and of bladder cancer). This trial offers evidence supporting rituximab use and demonstrating that it may be a safe alternative to cyclophosphamide in CTD-ILD patients. Future studies could examine its use as part of combination treatment for CTD-ILD patients. (Manfredi, A., et al. (2023). Rituximab for connective tissue disease-associated interstitial lung disease. Lancet Respir Med, 11(1), 3-4. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00356-3/fulltext?dgcid=raven_jbs_etoc_email; Maher, T. M., et al. (2023). Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomized, controlled, phase 2b trial. Lancet Respir Med, 11(1), 45-54. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00359-9/fulltext?dgcid=raven_jbs_etoc_feature_lanres#seccestitle10)Released: January 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - December 2022
A Small Risk of Interstitial Lung Disease Found with Use of Nonwarfarin AnticoagulantsA large nationwide population-based retrospective cohort study is the first to investigate the reported increased risk of interstitial lung disease (ILD) in patients with atrial fibrillation receiving direct oral anticoagulants (DOACs). These anticoagulants, which include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have been steadily displacing warfarin as the preferred anticoagulants for stroke prevention in atrial fibrillation. In clinical trials, cough and dyspnea were noted as adverse events, but ILD, a rare event, only became evident in large postmarketing studies and in case reports.READ MORE...Using the Taiwan National Health Insurance Research Database, the cohort study collected data on 106,044 patients (mean age, 73.4; 56.6% men) with nonvalvular atrial fibrillation (NVAF) and no preexisting chronic lung disease who received oral anticoagulation between June 2012 and December 2017; 60.9% of patients received one of the factor Xa inhibitors, 21.2% of patients received dabigatran, and 17.9% of patients received warfarin.After adjusting for patient differences at baseline, the factor Xa inhibitors as a group and individually were associated with a slightly greater risk of ILD compared to warfarin. The rate of incident ILD was 0.29 per 100 patient-years compared to 0.17 per 100 patient-years with warfarin (hazard ratio [HR], 1.54). Apixaban was associated with a rate of 0.35 per 100 patient-years, edoxaban with a rate of 0.37 per 100 patient-years, and rivaroxaban with a rate of 0.27 per 100 patient-years. Dabigatran was not associated with a greater risk of ILD on analysis. Concomitant use with amiodarone, which was frequent in this study, was associated with a higher risk of ILD regardless of the anticoagulant used; hazard ratios were as follows:· factor Xa inhibitors and amiodarone: HR, 1.41· dabigatran and amiodarone: HR, 1.62· warfarin and amiodarone: HR, 1.97Due to this study’s observational nature, it cannot definitively delineate the causal relationships it explores; additional research is needed to explore potential mechanisms. These results shouldn’t discourage clinicians from prescribing these drugs; numerous studies have demonstrated significant benefits with factor Xa inhibitors. On risk-benefit analysis, absolute increases in ILD with factor Xa inhibitors and dabigatran (-0.12 and -0.05 per 100 patient-years, respectively, vs. warfarin) were much smaller than the absolute reduction in ischemic stroke/systemic embolism (0.78 and 0.64 per 100 patient-years, respectively) and major bleeding (0.78 and 1.01 per 100 patient-years, respectively). The authors of the study recommend that clinicians vigilantly monitor any potential adverse lung outcomes associated with use of these drugs but note that there is no need to make any major changes to current practices. (Neale, T. (2022). Slight risk of interstitial lung disease seen with certain DOACs. tctMD. Retrieved November 2022 fromhttps://www.tctmd.com/news/slight-risk-interstitial-lung-disease-seen-certain-doacs; Chan, Y.-H., et al. (2022). Development of interstitial lung disease among patients with atrial fibrillation receiving oral anticoagulants in Taiwan. JAMA Netw Open, 5(11), e2443307. Retrieved November 2022 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798871)Released: December 2022Nursing Drug Handbook© 2022 Wolters KluwerFDA Suggests Possibility of OTC NaloxoneThe nonselective opioid receptor antagonist naloxone is a critical component of the effort to combat the opioid crisis. Naloxone reverses the effects of the respiratory depression and sedation produced by opioids; when administered at the first signs of opioid overdose (OD), it can prevent opioid-related deaths.READ MORE...The FDA has announced that it’s taking steps to encourage the development of nonprescription formulations of naloxone as a component of its FDA Overdose Prevention Framework. That framework has four priorities:· Support the primary prevention of overdose by limiting initial prescription drug exposure and inappropriate long-term prescriptions.· Encourage harm reduction through innovative programs (such as this initiative) and education.· Advance development of evidence-based treatment for substance use disorders.· Protect public from unapproved, diverted, or counterfeit drugs that present risk of OD.Naloxone is currently available as a prescription drug in the United States in several dosage strengths and dosage forms. It was originally approved as an injectable product for use by hospital personnel and first responders in the treatment of opioid OD, but increasingly has been used by non-health-care professionals, as initiatives sought to put naloxone into the hands of those who might witness an overdose. Since 2014 the FDA has approved several prescription naloxone drug and device combination products for use in emergency treatment of a known or suspected opioid OD; these are known as “community use” naloxone. In addition, as of 2020, every U. S. state and the District of Columbia have naloxone access laws, with one or more of these features:· Third-party provisions that allow providers to prescribe naloxone to someone not directly at risk of OD; that is, to a caregiver or family member· Standing-order provisions that allow for nonpatient-specific prescriptions· Immunity from civil and criminal prosecutions for prescribers and dispensers.Taken together, community-based naloxone distribution programs and naloxone access laws help to illustrate the potential public health benefits of nonprescription naloxone use.On preliminary assessment, naloxone nasal spray up to 4 mg, as well as naloxone autoinjector for IM or subcut use up to 2 mg, are the best candidates for nonprescription use. These dosage forms are used by most consumers. As of 2021, more than 90% of sales of naloxone were for the nasal spray form, although it should be noted that these sales numbers don’t consider donations of naloxone to community-based distribution programs, which are primarily autoinjector products.Although the benefits of broader use of naloxone are significant, concerns exist with making them available over the counter, such as associated risks that include adverse drug effects and precipitation of opioid withdrawal syndrome. Monitoring for and mitigation of these risks are important. The FDA must ensure that any products developed for nonprescription use are appropriately designed to support the intended users’ needs, including the packaging and labeling, and meet the requirements of the Food Drug and Cosmetic Act, demonstrating a clinically meaningful difference from the prescription product. The FDA has asked for comments on this proposal. (FDA. (2022, November 15). FDA announces preliminary assessment that certain naloxone products have the potential to be safe and effective for over-the-counter use [Press release]. Retrieved November 2022 from https://www.fda.gov/news-events/press-announcements/fda-announces-preliminary-assessment-certain-naloxone-products-have-potential-be-safe-and-effective; Federal Register. (2022). Safety and effectiveness of certain naloxone hydrochloride drug products for nonprescription use; request for comments. Retrieved November 2022 from https://www.federalregister.gov/documents/2022/11/16/2022-24874/safety-and-effectiveness-of-certain-naloxone-hydrochloride-drug-products-for-nonprescription-use)Released: December 2022Nursing Drug Handbook© 2022 Wolters KluwerDo Real-Time Prescription Benefits Recommendations Lower Costs for Patients?The rise in U. S. health care costs, especially out-of-pocket costs for patients, is a major driver for efforts to increase medication price transparency. Real-time prescription benefits (RTPB), an electronic clinical decision support tool, provides patient- and medication-specific out-of-pocket information to prescribers at the point of use. A study published in JAMA Internal Medicine demonstrates that such medication price transparency solutions that make cost information available to the prescriber and recommend clinically appropriate alternatives can be an effective tool for generating savings.READ MORE...In the cluster randomized trial, conducted in medical practices in a large academic health system in New York City, all outpatient prescriptions written were randomly assigned to a control arm or to an RTPB recommendation arm. Analysis was limited to those medications for which the tool could recommend an available alternative. Of the 867,757 outpatient prescriptions written at the practices over the study period (January to July 2021), 4.2% (36,419) met the criteria for analysis.If a prescription was randomized to the RTPB recommendation arm, the RTPB system recommended alternatives: either a different medication, different length of prescription, and/or a different choice of pharmacy. The prescriber could then opt for either the initial order or one of the recommended options. Electronic health record data were used to analyze the effect of the intervention on prescribing, both on out-of-pocket patient costs as well as on use of mail order pharmacy or 90-day supplies. Out-of-pocket costs includes any copay, coinsurance, and deductibles the patient is responsible for under their prescription benefits plan.The average out-of-pocket costs for a 30-day supply of medication in the intervention arm was $39.90; in the control arm, it was $67.80. Use of the RTPB recommendations resulted in an adjusted 11.2% reduction in costs. Mail-order pharmacy use was 9.6% in the intervention group and 7.6% in the control group; no differences were found in rate of use of 90-day medication supply.It’s hoped that, by controlling the patient’s out-of-pocket costs, the RTPB system can improve adherence and health outcomes. Further research will be needed to understand the impact of the system on other outcomes, such as prescribing behavior and adherence. (Desai, S. M., et al. (2022). Effects of real-time prescription benefit recommendations on patient out-of-pocket costs: A cluster randomized clinical trial. JAMA Intern Med, 182(11), 1129–1137. Retrieved November 2022 from https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2796059)Released: December 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - November 2022
Amifampridine an Effective Treatment for Spinal Muscle AtrophySpinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. The resulting deficiencies in the SMN protein lead to progressive lower motor neuron degeneration. Clinical severity in this disorder is variable, depending on the presence of the SMN2 gene, which can partially compensate for the SMN protein deficiency. Currently approved treatments for SMA target increasing SMN protein production by SMN2 (nusinersen, risdiplam) or reintroduce the SMN1 gene (gene therapy with onasemnogene abeparvovec).READ MORE...SMA-001, a phase 2, randomized, double-blind, placebo-controlled crossover study, explored a new avenue of treatment for SMA. Patients with SMA Type 3 commonly report fatigue and display a significant response on nerve stimulation studies, signs that suggest impaired neuromuscular junction (NMJ) transmission has a role in the disorder. Amifampridine, a voltage-dependent potassium channel blocker approved for treatment of Lambert-Eaton myasthenic syndrome, prolongs depolarization of the presynaptic NMJ terminal, enhancing neuromuscular transmission and muscle function.From January 2019 to September 2020, SMA-001 enrolled ambulatory patients with SMA Type 3 (able to walk unaided at least 30 meters) who had not received SMN-targeting therapies such as nusinersen. The study included 13 patients, 5 women and 8 men, mean age, 34.5 years. Patients first entered a run-in phase, in which amifampridine was individually titrated up to a maximal effective dose, but no higher than 80 mg/day. Then, those who achieved at least a 3-point improvement in the Hammersmith Functional Motor Score Expanded (HFMSE) were randomly assigned to amifampridine or placebo in a 28-day blinded crossover phase. Patients were assigned to amifampridine/placebo or placebo/amifampridine sequence, which they took for 2 weeks, then switched to the other, with no washout period. The dosage of amifampridine given in this crossover phase was that determined for each individual in the run-in phase. During weekly clinic visits, the HFSME was administered, as were a number of timed tests of motor skills and quality of life assessments.Statistically significant improvement in HFMSE was observed in patients taking amifampridine compared to placebo (mean difference, 0.792). This effect is small, but the fact that the HFMSE score had already improved by at least 3 points before randomization might explain that. However, no significant differences were observed in results of timed tests. In quality-of-life measures, statistically significant improvement was observed in the fatigue subscale, as well as a significant reduction in the expected treatment subscale, but for all other subscale scores, differences were nonsignificant. No serious adverse events were reported, and treatment adherence was high throughout the study.Results provided Class II evidence that amifampridine is safe and effective in treating ambulatory SMA Type 3 patients, demonstrating that fostering neuromuscular transmission can improve fatigability in these patients. The study findings were limited by the small sample size and the brevity of the study, since SMA Type 3 doesn’t typically progress rapidly. Larger, well-powered studies may better define the role of amifampridine as adjunctive treatment to SMN-enhancing treatments. (Bonanno, S., et al. (2022). Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: A randomized, placebo-controlled, crossover phase 2 trial. J Neurol, 269, 5858–5867. Retrieved November 2022 from https://link.springer.com/article/10.1007/s00415-022-11231-7)Released: November 2022Nursing Drug Handbook© 2022 Wolters KluwerEtrolizumab for Crohn DiseaseResults of BERGAMOT, a randomized, double-blind, phase 3 study published in The Lancet Gastroenterology and Hepatology, demonstrated that maintenance treatment with etrolizumab, an antibody against β7 integrin, produced significantly higher rates of clinical remission in patients with moderate to severe Crohn disease. The study, conducted at 326 treatment centers worldwide, compared the safety and efficacy of etrolizumab, in two dosage strengths, with placebo as both induction and maintenance therapy.READ MORE...The study, conducted from March 2015 through September 2021, enrolled patients ages 18 to 80 with moderate to severe active Crohn disease, as defined by a Crohn Disease Activity Index (CDAI) score between 220 and 480, mean daily stool frequency score greater than or equal to 6, or daily stool frequency score greater than or equal to 3 and mean daily abdominal pain score greater than or equal to 1, and presence of active inflammation on ileocolonoscopy. The patients also had intolerance to or inadequate or no response to treatment with corticosteroids, immunosuppressants, or anti-TNF therapy within the past 5 years.BERGAMOT consisted of three induction cohorts (a placebo-controlled, double-blind exploratory cohort; an active cohort without placebo control; and a placebo-controlled, double-blind pivotal cohort) and a maintenance cohort. This report discusses the findings of cohort 3, in which 385 patients were randomly assigned to placebo (n = 97), 105 mg etrolizumab subcutaneously every 4 weeks (n = 143), or 210 mg etrolizumab subcutaneously every 4 weeks (n = 145). At week 14 of induction therapy, patients from all three cohorts who had a response to etrolizumab as measured by CDAI-70 were rerandomized to receive 105 mg etrolizumab or placebo as maintenance every 4 weeks for 52 weeks. As a result, 434 patients took part in the maintenance phase, 217 in the placebo arm, and 217 in the etrolizumab arm.The researchers determined the proportion of patients who entered clinical remission, defined as mean daily stool frequency less than or equal to 3 and mean daily abdominal pain less than or equal to 1, with no worsening, and the proportion who demonstrated endoscopic improvement, as shown by greater than or equal to 50% reduction in Simple Endoscopic Score for Crohn’s Disease (SES-CD). At week 14, 48 patients (33%) in the 210-mg induction group versus 28 patients (29%) in the placebo group were in clinical remission (adjusted treatment difference, 3.8%). Endoscopic improvement was seen in 40 patients (27%) in the 210-mg induction group vs. 21 patients (22%) in the placebo group (adjusted treatment difference, 5.8%). At week 66 of maintenance treatment, significantly higher proportions of patients receiving etrolizumab than those receiving placebo were in clinical remission: 76 patients (35%) in the etrolizumab maintenance group versus 52 patients (24%) on placebo (adjusted treatment difference, 11.3%). Significantly higher proportions of patients in the etrolizumab arm showed endoscopic improvement: 51 patients (24%) vs. 26 patients (12%) in the placebo arm (adjusted treatment difference, 11.5%).These findings demonstrate a significantly higher incidence of clinical remission and endoscopic improvement in patients with moderate to severe Crohn disease during the maintenance phase of treatment with etrolizumab, but not during induction. (Sandborn, W., et al. (2022). Etrolizumab as induction and maintenance therapy in patients with moderately to severe active Crohn’s disease (BERGAMOT): A randomized, placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. Advance online publication. Retrieved November 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(22)00303-X/fulltext)Released: November 2022Nursing Drug Handbook© 2022 Wolters KluwerAbnormal Menstrual Bleeding Associated with Anticoagulant for Acute VTEAbnormal uterine bleeding (AUB) is common among women of reproductive age treated with anticoagulants for acute venous thromboembolism (VTE), with a considerable negative impact on quality of life (QOL). The TEAM-VTE study, an international multicenter prospective cohort study in patients of reproductive age (18 to 50) diagnosed with acute VTE, was conducted at 12 hospitals across 8 European countries between August 2018 and September 2021. The study, published in the journal Blood, aimed to quantify the burden of AUB and to identify unmet clinical needs in patients receiving anticoagulant therapy.READ MORE...From August 2018 to March 2021, 98 patients with confirmed symptomatic first or recurrent VTE and active menstrual cycles, with a mean age of 34, were enrolled shortly after diagnosis of VTE (before the first day of the next menstrual cycle after VTE diagnosis or within 1 month of diagnosis) and were followed until discontinuation of anticoagulant treatment or 6 months, whichever came first. If AUB was discovered, a diagnostic workup was performed to rule out other causes of the bleeding. The patients were followed using various measures:· Menstrual blood loss for the last menstrual cycle before VTE and then for each cycle in the 3 to 6 months of follow-up was measured by pictorial blood loss assessment charts (PBAC), a validated self-reporting tool.· AUB-related QOL was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire (MBQ); these were available for 74 women.Patients were followed for recurrence of symptomatic VTE, any bleeding event other than AUB, and all-cause mortality, and were managed according to accepted guidelines and local preference. The researchers noted which anticoagulant was administered to treat the VTE in these patients; 78 were treated with oral direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), 13 with vitamin K antagonists (warfarin) or low-molecular-weight heparins, and 7 with the direct thrombin inhibitor dabigatran.Overall, AUB as defined by one of three accepted measures (PBAC score greater than 100, PBAC score greater than 150, or self-report) occurred in 66% of patients at any time during the follow-up period; for 90% of them, this occurred within the first 2 months after VTE diagnosis. Among women without AUB before VTE based on retrospective PBAC scores (assessing blood loss during the last menstrual cycle before VTE diagnosis), new-onset AUB occurred in 60% (37% of the overall population of study) in those with retrospective PBAC less than or equal to 100, and in 63% (43% of the overall population) in those with retrospective PBAC less than or equal to 150.The median PBAC score increased during the first menstrual cycle compared with the retrospective PBAC (median PBAC before VTE was 35 and for first menstrual cycle was 95). After the first menstrual cycle, the amount of blood loss decreased gradually, followed by median PBAC scores that remained stable in the 2nd through 6th cycles at about twice the retrospective PBAC score. The observational design of the study and the low number of patients exposed to the different anticoagulants prevent drawing any definitive conclusions about differences among the oral anticoagulants; however, patients treated with dabigatran showed no increase in blood loss during the first cycle, in contrast to patients treated with either oral direct factor Xa inhibitors, vitamin K antagonists, or low-molecular-weight heparin.The overall QOL decreased significantly over time, with a mean increase in MBQ score of 5.1 points between baseline and cessation of anticoagulation or 6-month follow-up. On analysis, the decrease in QOL was observed only among those who had new-onset AUB, with mean difference in MBQ score of +9.2 points for those with new-onset AUB versus those without AUB and of +9.3 points for those with new-onset AUB versus those who had experienced AUB before VTE.These findings support the proposed association of incident AUB with anticoagulation and highlight the critical need to include assessment of AUB in daily practice. It should increase awareness and should lead to development of evidence-based strategies to routinely and adequately prevent and treat incident AUB in this setting. (de Jong, C. M. M., et al. (2022). Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism. Blood, 140(16), 1764–1773. Retrieved November 2022 from https://ashpublications.org/blood/article/140/16/1764/486115/Incidence-and-impact-of-anticoagulation-associated)Released: November 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - October 2022
Centanafadine in Adults with Attention Deficit Hyperactivity DisorderAttention deficit hyperactivity disorder (ADHD) likely results from dysregulation of the complex interplay of adrenergic and dopaminergic neurotransmission, resulting in deficits in executive function, reward processing, and attention. Centanafadine, a stimulant with nonstimulant characteristics that acts by inhibiting reuptake of norepinephrine, dopamine, and serotonin, is being investigated for use in adults with ADHD.READ MORE...A report in the Journal of Clinical Psychopharmacology describes the first large-scale studies to demonstrate the safety and efficacy of centanafadine in adults with ADHD. The two phase 3 randomized, double-blind, placebo-controlled, parallel-group studies were conducted from January 2019 through early 2020 in 45 clinical sites in the United States. To limit placebo effect, both studies were designed with a single-blind placebo run-in period, in which subjects who experienced an improvement in symptoms didn’t move on to randomization. The studies then randomized subjects to receive 200 mg/day of centanafadine sustained-release tablets (n = 149 study 1, 145 study 2); 400 mg/day of centanafadine sustained-release tablets (n = 149 study 1, 143 study 2); or placebo (n = 148 study 1, 142 study 2). Patients in both studies had moderate to severe ADHD at baseline (mean Adult ADHD Investigator Symptom Rating Scale [AISRS] total score, 38.7).Investigators determined change from baseline at day 42 in AISRS total score and in the Clinical Global Impression-Severity of Illness Scale (CGI-S). At day 42, statistically significant improvement in AISRS total score was achieved for both dosages compared with placebo in both studies. The AISRS total scores at day 42 were reduced by 25.5% in study 1 and 32.2% in study 2 for the 200-mg dose, by 24.6% in study 1 and 32.2% in study 2 for the 400-mg dose, compared to 17.7% in study 1 and 21.4% in study 2 for placebo. The differences in AISRS for centanafadine vs. placebo were as follows:• Study 1: -3.16 for 200 mg, -2.74 for 400 mg• Study 2: -4.01 for 200 mg, -4.42 for 400 mgThese differences were seen as early as day 28 and persisted throughout the study. Both dosages also produced statistically significant improvements in CGI-S score vs. placebo at day 42, as follows:• Study 1: -0.27 for 200 mg, -0.28 for 400 mg• Study 2: -0.33 for 200 mg, -0.28 for 400 mgThe overall rate of treatment-emergent adverse events was low, but there was a small increase noted with increases in centanafadine dose. The most common were headache and decreased appetite, which were considered mild or moderate.These trials were affected by the COVID-19 pandemic; study protocols had to be altered in late March 2020. As of March 23, study 1 had met its targets, so subjects still in treatment were withdrawn and continued to the safety follow-up phase, but study 2 had not yet met its completed-subject targets. All subjects who had not been randomized yet had treatment discontinued, and those who had been randomized continued to study completion, unless they tested positive for COVID. As a result, 348 subjects completed study 1 and 336 completed study 2. The most reported reason for discontinuation in study 1 was protocol deviation (5.6%), followed by adverse effects (4.1%) and withdrawal by subject (3.2%); in study 2 it was “other, not COVID-related” (6.6%), followed by withdrawal by subject (4.5%) and adverse effects (3.0%). Nine subjects in each study withdrew for reasons related to COVID-19.But despite these restrictions, the results still reached statistical significance. Future studies should determine long-term safety and should compare centanafadine to other available therapies for adults with ADHS. (Lenard, A., et al. (2022). Efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder: Results of 2 phase 3, randomized, double-blind, multicenter, placebo-controlled trials. J Clin Psychopharmacol. 42(5), 429–439. Retrieved October 2022 from https://journals.lww.com/psychopharmacology/Fulltext/2022/09000/Efficacy,_Safety,_and_Tolerability_of.2.aspx)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer Mepolizumab Significantly Reduced Asthma Exacerbations in Children at High RiskResearch has shown that therapies directed at the eosinophilic phenotype reduced asthma exacerbations in adults, but the effect on children was not as clear. Economically disadvantaged Black American and Hispanic American children are among those with the highest risk of morbidity and mortality associated with asthma, but there is scant data available on effective strategies in this vulnerable population. A new study demonstrates that adjunctive treatment with the humanized monoclonal antibody mepolizumab significantly reduced the number of asthma exacerbations in urban Black American and Hispanic American children. The study, MUPPITS-2 (Mechanisms Underlying Asthma Exacerbations Prevented and Persistent with Immune-based Therapy), was published in The Lancet.READ MORE...Between November 2017 and mid-March 2020, 290 children and adolescents were enrolled in the double-blind, placebo-controlled study, which was conducted at nine urban medical centers in the United States. The researchers enrolled children and adolescents ages 6 to 17 years who lived in socioeconomically disadvantaged neighborhoods and had exacerbation-prone asthma (that is, at least two exacerbations in the prior year) and blood eosinophil count of at least 150 cells/microliter. Median age of participants was 10 years; 55% were boys; approximately 70% were Black American and approximately 25% were Hispanic American. Median household income was $1,250 or less/month in 37% to 40% of participants, and between $1,251 and $2,500/month in 32% to 37% of participants. The children were randomly assigned to mepolizumab (n = 146) or to placebo (n = 144) injections once every 4 weeks for 52 weeks. The dosage of mepolizumab varied by age: 40 mg was given to those ages 6 to 11 years, and 100 mg was given to those ages 12 to 17 years. All participants also continued to receive guideline-based care for their asthma. The researchers aimed to determine whether adding mepolizumab to guideline-based care reduced the number of asthma exacerbations treated with systemic steroids during the 52 weeks of therapy.The average number of asthma exacerbations requiring treatment with systemic steroids fell significantly during the 52 weeks of the study. Among children and adolescents treated with mepolizumab, the number of exacerbations was 0.96; with placebo, it was 1.30. Relative decrease in these patients was 27%. Blood eosinophil levels were markedly reduced in patients who received mepolizumab, from a mean of more than 400 cells/microliter at baseline to less than 200 cells/microliter by week 8. These levels remained over 400 cells/microliter in placebo-treated children. Time to first asthma exacerbation wasn’t significantly different between the two groups, and no differences were shown in other asthma outcomes (lung function, change in disease severity). On patient global assessment, 84% of participants treated with mepolizumab and 89% of those treated with placebo self-reported clinically moderate or significant disease improvements. Study clinicians completed that same assessment and found improvement among 66% treated with mepolizumab and 71% treated with placebo.Researchers concluded that these findings highlighted the importance of evaluating treatment response in urban Black American and Hispanic American children, populations that are typically underrepresented in clinical trials. (Jackson, D. J., et al. (2022). Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): A randomised, double-blind, placebo-controlled, parallel-group trial. JAMA, 400(10351), P502–P511. Retrieved October 2022 fromhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01198-9/fulltext; Slomski, A. (2022). Mepolizumab cuts asthma exacerbations among high-risk kidsJAMA, 328(12), 1171–1172. Retrieved October 2022 from https://jamanetwork.com/journals/jama/fullarticle/2796694)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer Obesity May Potentiate Risk of Thrombotic Events in Users of Oral ContraceptivesDespite the understanding that obesity and estrogen-containing contraceptives are independent risk factors for cardiovascular (CV) complications, a significant number of women with obesity continue to be prescribed these products for contraception. A review of current literature published in ESC Heart Failure, a journal from the European Society of Cardiology, provides evidence that obesity can potentiate CV risks—especially of venous thromboembolism (VTE)—in women of reproductive age taking combination oral contraceptives (COCs).READ MORE...The review examined the latest evidence and ongoing research on the CV impact of both obesity and contraceptive use, with a specific focus on clinical implications. An Italian review article cited a large population-based study showing that a body mass index (BMI) greater than 25 but less than 30 was associated with a 1.7-fold increased risk of VTE and a BMI above 30 was associated with a 2.4-fold increased risk. The study showed that when these subjects took COCs, risks increased to 12-fold in the group with BMI between 25 and 30 and to 24-fold in the group with BMI over 30 when compared to women who are nonobese not taking COCs. Another study was a meta-analysis that determined odds ratios (ORs) of VTE in women using COCs and showed that OR increased with BMI. When compared with COC users with BMI between 20 and 24.9, the odds of VTE in women using COC with BMI between 30 and 34.9 was 1.8 and in those with BMI of 35 or greater was 3.1. Another study showed that obesity has a greater impact on CV risk in women younger than age 40, the population that uses contraception; the risk of thrombosis in these individuals is 6.1 times higher than the risk in women who are nonobese. In addition, risk of drug-induced thrombosis can be dependent on the duration of drug therapy, a relevant issue with COCs, since users typically take them long-term.These findings should spur conversations between clinicians and young women early in their reproductive years to enable them to understand the risks and to make lifestyle and contraceptive choices that can minimize these risks. Women with a BMI over 30 taking COCs should be viewed as an at-risk population and should be advised to avoid other CV risk factors as primary prevention. In addition, clinicians should prioritize long-acting reversible methods of contraceptives such as intrauterine devices and subdermal implants, both for safety and effectiveness, in these patients. (McKeown, L. A. (2022). Obesity may boost thrombotic events in contraceptive users, review suggests. TCTMD. Retrieved October 2022 from https://www.tctmd.com/news/obesity-may-boost-thrombotic-events-contraceptive-users-review-suggests; Rosano, G. M. C., et al. (2022). Obesity and contraceptive use: Impact on CV risk. ESC Heart Failure. Advance online publication. Retrieved October 2022 from https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.14104)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer CDC Analysis Indicates Need for Improvements in Management of Children with Sickle Cell AnemiaAnalysis of Medicaid data on more than 3,300 children with sickle cell anemia demonstrated that many of these at-risk children are not receiving potentially lifesaving screening and treatment related to their disease. Sickle cell anemia is the most severe form of sickle cell disease, a disorder that results in misshapen, sticky red blood cells that break down easily, blocking blood flow and therefore resulting in impaired oxygenation of body tissues. The Centers for Disease Control and Prevention (CDC), which published this report, notes two health care measures are important in preventing complications in children with sickle cell anemia:READ MORE...Transcranial Doppler (TCD) ultrasound screening, which identifies children at risk for strokeHydroxyurea, a myelosuppressive agent, which reduces the occurrence of several complications of sickle cell anemia, including severe acute pain episodes and acute chest syndrome, which can result in lung injury and trouble breathingSickle cell anemia is a leading cause of stroke, but data showed that fewer than half of children with the disorder received the recommended stroke screening in 2019. The CDC’s analysis of 2019 Medicaid data showed that only 38% of children with sickle cell anemia ages 10 to 16 and 47% of those ages 2 to 9 had undergone TCD ultrasound screening. In addition, only 2 in 5 children ages 2 to 9 received hydroxyurea, the recommended treatment. The CDC study showed that in 2019, 53% of those ages 10 to 16 and 38% of those ages 2 to 9 were prescribed hydroxyurea. Stroke screening and hydroxyurea use were highest among children with high levels of health care use and those with prior complications.These results reflect the barriers to care of sickle cell patients, including structural racism. Patients lack access to providers with expertise in treating the disease and report having their symptoms dismissed or being stigmatized when they do engage with the health care system. In addition, both family members and providers hesitate to make use of hydroxyurea due to fear of potential side effects and uncertainty about its effectiveness.The CDC recommends that clinicians take steps to ensure that children with sickle cell anemia receive this important screening and this potentially lifesaving treatment. Among their recommendations:Increase TCD stroke screening by educating patients and families about the risk of stroke and the screening, identifying barriers to access (transportation, finances) and taking steps to alleviate them.Make stroke screening part of a single comprehensive visit when possible, and track TCD ultrasound screenings and follow-up in electronic health records.Encourage the patient and family to discuss with a health care provider the results of the TCD ultrasound screening and the next steps to take if the results indicate a greater risk of stroke.Become familiar with the guidelines on prescribing hydroxyurea and with studies showing the safety of the drug in these patients.To encourage adherence and follow-up, address barriers to patient access and incorporate reminders into the electronic health record.Educate the patient and family about hydroxyurea and the pros and cons of adherence to treatment protocol, and develop tools to help patients take hydroxyurea as directed.(CDC. Media Statements. (2022). Many children with sickle cell anemia not receiving lifesaving screening and treatment. Retrieved October 2022 from https://www.cdc.gov/media/releases/2022/s0920-vs-sickle-cell-anemia.html; CDC. Vital Signs. (2022). Preventing sickle cell complications in children. Retrieved October 2022 from https://www.cdc.gov/vitalsigns/sickle-cell-anemia/)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - September 2022
Evening Dosing of Antihypertensive Not Superior to Morning DosingA randomized UK trial in more than 21,000 patients with hypertension has challenged the long-standing belief that evening doses of antihypertensive medications lead to better outcomes. Results of the trial TIME (Treatment In Morning vs. Evening), a large, prospective, randomized trial that tested whether evening doses of antihypertensives improved major CV outcomes compared with morning dosing, were presented at the European Society of Cardiology Congress in Barcelona.READ MORE...Adults taking antihypertensive medications in the UK who had a valid e-mail address were recruited and followed for more than 5 years. After signing up on the trial website, participants were randomized, 10,503 to evening dosing and 10,601 to morning dosing. Average age of patients was 65; 58% were men and 98% were white. Information on outcomes was obtained from e-mail contact with participants and through record linkages to national databases. Further data was gathered from family doctors and hospitals in the UK and was adjudicated by a blinded committee.The composite endpoint for the study was hospitalization for nonfatal MI, nonfatal stroke, or vascular death. This occurred at similar frequencies regardless of the time of medication administration: 362 participants (3.4%) in the evening dosing group and 390 participants (3.7%) in the morning dosing group experienced these outcomes, for an unadjusted hazard ratio (HR) of 0.95. Other outcomes also showed that neither time of antihypertensive dosing was superior to the other. These outcomes include:Nonfatal stroke: HR, 0.93Nonfatal MI: HR, 0.92CV death: HR, 1.1All-cause mortality: HR, 1.04During the presentation, researchers concluded that patients can take their regular antihypertensive medications at a time of day that is convenient and works for them. (Practical Cardiology. (2022). TIME study: No added benefit from nighttime dosing of blood pressure medications. Retrieved August 2022 from https://www.practicalcardiology.com/view/time-study-no-added-benefit-from-nighttime-dosing-of-blood-pressure-medications; European Society of Cardiology. (2022). Evening dosing of blood pressure medication not better than morning dosing. Press release. Retrieved August 2022 from https://www.escardio.org/The-ESC/Press-Office/Press-releases/Evening-dosing-of-blood-pressure-medication-not-better-than-morning-dosing) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerCDC Report Details Safety of COVID-19 Booster Doses for Children Ages 5 to 11A report from the Centers for Disease Control and Prevention (CDC) published in MMWR detailed the findings of safety monitoring of COVID-19 vaccine booster doses administered to children ages 5 to 11. On May 17, 2022, the FDA authorized a booster dose of the Pfizer-BioNTech COVID-19 vaccine under Emergency Use Authorization for children ages 5 to 11 years, to be given 5 months after receipt of the second primary series dose. Approximately 650,000 booster doses were administered to individuals in this age group in the first 10 weeks of rollout (May 17 to July 31).READ MORE...Safety data were obtained from v-safe, a voluntary smartphone-based safety surveillance system established to monitor adverse events after COVID-19 vaccination, and from VAERS (Vaccine Adverse Event Reporting System), a national passive vaccine safety surveillance system comanaged by the CDC and FDA. Through v-safe, health surveys are sent daily to registrants during the first week after vaccine administration, with questions about potential local injection-site reactions and systemic reactions as well as health inputs. If parents indicate on the survey that they sought medical care for their child after vaccination, the CDC’s v-safe call center contacts them and encourages completion of a VAERS report. VAERS was developed to monitor adverse events after vaccination; it accepts reports from health care providers, vaccine manufacturers, and members of the public. Serious events that are included in the report include hospitalization, life-threatening illness, permanent disability, congenital anomalies/birth defects, or death.During those first 10 weeks, approximately 657,302 U.S. children received a third (booster) dose of the Pfizer-BioNTech vaccine; 3,249 reports were made to v-safe for children in this age group. Both local injection-site reactions (n = 2,224) and systemic reactions (n = 1,483) were reported; the prevalence of both was similar to that seen after the second dose of the vaccine:Local reactions: 68.5% booster, 68.0% second doseSystemic reactions: 45.6% booster, 45.8% second doseThe most frequently reported adverse events were injection-site pain (n = 2,166), fatigue (n = 938), and headache (n = 647); most were mild and were most frequently reported the day after vaccination. In the week after receiving the booster, 225 enrolled children were unable to attend school, and 392 were unable to complete daily activities. The inability to attend school was reported less frequently than after the second dose (6.9% vs. 10.0%), but inability to complete daily activities was reported more frequently (12.1% vs. 7.5%).VAERS received 581 reports of adverse events after receipt of the booster by children ages 5 to 11; 578 (99.5%) of these reports were considered nonserious. The most commonly reported events (71.1%) were vaccine administration errors (such as preparation errors, incorrect dose, and inappropriate age). Local and systemic reactions were common among the VAERS reports, but no reports of myocarditis or death were received. Only three serious reports were made to VAERS: new-onset diabetes 10 days after vaccination, facial swelling 3 days after vaccination, and pain, fatigue, and malaise 5 days after vaccination.These findings may change somewhat over time, as safety monitoring continues, more school-age children receive boosters, and as vaccine providers gain additional experience with pediatric doses of COVID-19 vaccines. Continued education of vaccine providers might reduce the errors reported to VAERS. (Hause, A. M., et al. (2022). Safety monitoring of Pfizer-BioNTech COVID-19 vaccine booster doses among children aged 5-11 years – United States, May 17 – July 31, 2022. MMWR, 71(33): 1047–1051. Retrieved August 2022 from https://www.cdc.gov/mmwr/volumes/71/wr/mm7133a3.htm) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerOlokizumab Effectiveness Expands Treatment Options for Rheumatoid ArthritisA new drug for rheumatoid arthritis (RA) has been shown to be at least as effective as the current gold standard treatment. Currently, if a patient’s disease progresses on initial therapy with the folic acid antagonist methotrexate, combination therapy with the tumor necrosis inhibitor adalimumab plus methotrexate is administered. Olokizumab is a monoclonal antibody that targets IL-6, which is known to play a role in the inflammatory process and in the progression of joint damage in RA.READ MORE...CREDO2 (Clinical Rheumatoid Arthritis Development of Olokizumab) was a Phase III, double-blind, randomized, placebo- and active-controlled, international trial conducted from May 2016 through November 2019 at 209 sites worldwide. Results of the multicenter study, published in the New England Journal of Medicine, compared treatment with olokizumab plus methotrexate to placebo and to the gold standard, adalimumab plus methotrexate, testing for superiority to placebo and for noninferiority to adalimumab.The study randomly assigned patients with RA and inadequate response to initial methotrexate treatment to receive olokizumab 64 mg every 2 weeks (n = 464), olokizumab 64 mg every 4 weeks (n = 479), adalimumab 40 mg every 2 weeks (n = 462), or placebo (n = 243). All patients continued receiving methotrexate. Patients were followed to determine if they met the criteria for an American College of Rheumatology 20 (ACR20) response by week 12. Such a response entails at least 20% fewer tender or swollen joints and an improvement of at least 20% in 3 of 5 treatment domains:Patient’s global assessment of disease activityPatient’s assessment of painProvider’s global assessment of disease activityPatient function according to score on Health Assessment Question-Disability IndexC-reactive protein level.Results demonstrated that, in patients with RA who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing ACR20 response at week 12. The proportion of patients who reached ACR20 response at 12 weeks was 44.4% with placebo, 70.3% with olokizumab every 2 weeks, 71.4% with olokizumab every 4 weeks, and 66.9% with adalimumab. Both dosages of olokizumab were considered noninferior to adalimumab on this measure.The percentage of patients with a Disease Activity Score 28 of less than 3.2 (a measure of acute inflammation) at week 12 was 12.8% of those receiving placebo, 45.3% of those receiving olokizumab every 2 weeks, 45.7% of those receiving olokizumab every 4 weeks, and 38.3% of those receiving adalimumab. The percentage of patients who achieved remission, as assessed by Clinical Disease Activity Index score of 2.8 or less at week 24, was 41.4% with placebo, 11.2% with olokizumab every 2 weeks, 12.1% with olokizumab every 4 weeks, and 13.0% with adalimumab. Adverse events occurred in approximately 70% of patients and were most commonly infections that were mild to moderate in severity.These results offer another option for treatment for patients with RA, up to 25% of whom don’t respond well to current treatment options. Larger and longer trials are needed to further elucidate the safety and efficacy of olokizumab in RA. (Smolen, J. S., et al. (2022). Olokizumab versus placebo or adalimumab in rheumatoid arthritis. New Engl J Med, 387: 715–726. Retrieved August 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2201302) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerUpdated Recommendations for Statin Use for Primary Prevention of Cardiovascular DiseaseUpdated recommendations for use of statins as primary prevention of atherosclerotic cardiovascular disease (CVD) in adults have been published by the U.S. Preventive Services Task Force (USPSTF) in JAMA. These recommendations were based on review of evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality and all-cause mortality in adults age 40 and older without a previous history of CVD and no signs or symptoms of CVD who were considered at risk.READ MORE...In pooled analysis, statins were associated with a decreased risk of all-cause mortality (18 trials), relative risk (RR), 0.92; of fatal or nonfatal stroke (15 trials), RR, 0.78; of fatal or nonfatal MI (12 trials), RR, 0.67; and with a decreased risk of composite CV outcomes (15 trials), RR, 0.72. No significant harm was associated with statin use in these studies, suggesting a significant overall benefit to their use as primary prevention.Based on this analysis, USPSTF makes the following clinical recommendations:Clinicians should prescribe statins as preventive for CVD in adults ages 40 to 75 who have at least one risk factor for CVD and a 10-year CVD event risk of 10% or greater; the analysis showed with moderate certainty that use of statins in this population had at least a moderate net benefit.Clinicians can selectively offer statins to those ages 40 to 75 with at least one CVD risk factor and a 10-year CVD event risk between 7.5% and 10%, taking the patient’s values and preference into account, as well as the presence of factors not included in the original risk assessment; the analysis showed with moderate certainty that use of statins in this population had a smaller net benefit.Evidence is insufficient to determine how beneficial it would be to prescribe statins as primary prevention for CVD events and mortality in adults age 76 or older with no history of CVD. Such use would be at the discretion of the clinician, taking other factors into consideration.The analysis also demonstrates directions for research, including improving the accuracy of CVD risk prediction in all racial, ethnic, and socioeconomic groups, gaining a clearer picture of the benefits and harms of statins as primary prevention in older adults, and determining the efficacy and safety of long-term statin use in younger adults, as well as examining the effects of early versus delayed initiation of statin therapy for primary prevention of CVD disease. (US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. (2022). JAMA, 328(8): 746-753. Retrieved August 2022 from https://jamanetwork.com/journals/jama/fullarticle/2795521) Released: September 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - August 2022
Need for Access to Contraception Still Unmet for Many WomenThe Family Planning 2020 Initiative set a goal of increasing the number of women using modern contraceptives by 120 million in priority countries. A new report in The Lancet estimates that this number increased by 69 million in these countries, which would fall 51 million short of that goal. In the study, part of the systematic analysis for the Global Burden of Disease Study 2019, higher rates of contraceptive coverage were linked with the availability of a diverse range of contraceptive choices. This study elucidates the major increases in contraceptive use and the reductions in unmet need that have occurred since 1980.READ MORE...Researchers examined 1,162 population-based surveys of contraceptive use by women of reproductive age (ages 15 to 49) who self-reported current use of contraceptives for family planning. Using regression analysis, they determined estimates of the contraceptive prevalence rate (CPR) and modern CPR (mCPR), whether the demand for contraception was satisfied, and the contraceptive method mix, and examined them in both partnered and unpartnered women in five age groups.Between 1970 and 2019, increases were observed in use of all contraceptives (CPR), increasing by 18.7 percentage points, and that of mCPR, by 20.1 percentage points. The demand satisfied increased by 24.3 percentage points. In 2019, the average CPR was 51.9%, average of mCPR was 47.7%, and demand satisfied was 79.1%, although there were considerable differences geographically.Women ages 15 to 24 accounted for 16.0% of total need but 26.5% of global unmet need. The lowest rate of demand satisfied was found in women ages 15 to 19 (64.8%), followed by those ages 20 to 24 (71.9%); 43.2 million women ages 15 to 24 had unmet needs for contraception in 2019. These lower rates of satisfied demand in young women are cause for concern because of the effects both on the women themselves and society in general. Use of contraception is associated with reductions in maternal and neonatal mortality due to the avoidance of unintended and adolescent pregnancies, and access to contraceptives supports pursuit of education and economic opportunities. To address these disparities, family planning programs must determine the accessibility and acceptance of existing methods in use by other women among this younger age group.The methods women used to meet their contraception needs differed by marital status, age, and region. Compared with partnered women of all ages, unpartnered women more commonly used oral contraceptive pills and condoms; long-acting reversible methods (such as, IUDs, contraceptive implants, or injections) tended to be used most by women ages 20 to 49, and older women were more likely to use female sterilization.The absence of contraceptives tailored to the needs of younger women might be one explanation for the unmet need in that population; for example, if female sterilization is the method most often available, it’s unlikely to appeal to young women who haven’t had children yet. (Haakenstad, A., et al. (2022). Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400(10348), 295–327. Retrieved July 2022 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00936-9/fulltext#seccestitle210)Released: August 2022Nursing Drug Handbook© 2022 Wolters KluwerMacrolide Antibiotics May Be Associated with Hearing Loss in ChildrenMacrolides are one of the most used medications in children, with the most frequently prescribed being azithromycin, clarithromycin, and erythromycin. A retrospective case-control study published in JAMA Otolaryngology–Head and Neck Surgery attempted to determine whether that outpatient macrolide treatment was associated with pediatric sensorineural hearing loss. Past research has linked sensorineural hearing loss in adults to prior use of high-dose or IV macrolide treatment, but it hasn’t been studied in children.READ MORE...Using data from TRICARE, the health insurance system for U.S. uniformed service members and their families, the study analyzed 875 matched pairs of children, adolescents, and young adults with and without sensorineural hearing loss from records of outpatient encounters from October 2009 to September 2014. They were matched by age, sex, and time elapsed since the date of antibiotic prescription. Mean age was 5.7 years; patients were 62% male, and 66% non-Hispanic white. Multivariate logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders.They found that compared with peers without hearing loss, pediatric patients with sensorineural hearing loss were more likely to have received a prescription for a macrolide antibiotic compared to one for penicillin (adjusted odds ratio [aOR], 1.31). The odds were significantly higher when more than 180 days had elapsed between antibiotic exposure and the patient’s testing and diagnosis of hearing loss (aOR, 1.79).Currently, 56% of pediatric sensorineural hearing loss is considered idiopathic; this study suggests that macrolides warrant further study as potential risk factors. The results could also guide practice by encouraging early recognition of sudden hearing loss after macrolide use, given the success rate of prompt hyperbaric oxygen treatment for these patients. (Lopilato, J. (2022). Kids’ hearing loss associated with common antibiotics. MedPage Today. Retrieved July 2022 from https://www.medpagetoday.com/pediatrics/generalpediatrics/99855; Dabekaussen, K. F., et al. (2022). Association of outpatient oral macrolide use with sensorineural hearing loss in children, adolescents, and young adults. JAMA Otolaryngol—Head Neck Cancer. Retrieved July 2022 from https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2794472?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF)Released: August 2022Nursing Drug Handbook© 2022 Wolters KluwerOntamalimab Showed Sustained Treatment Response in Crohn DiseaseIn a substantial number of patients with Crohn disease, nonresponse or loss of response to the approved treatments results in an unmet need for novel treatments with a good safety profile and more durable efficacy. OPERA-II, a multicenter, open-label phase 2 extension study, examined the long-term safety and efficacy of one of these treatments, ontamalimab, a fully human IgG monoclonal antibody against mucosal addressin cell adhesion molecule-1.READ MORE...All patients in the study had completed 12 weeks of treatment in OPERA, a phase 2, double-blind, placebo-controlled trial that examined three dosage strengths of ontamalimab (22.5 mg, 75 mg, or 225 mg) and compared clinical response and remission in 265 patients with Crohn disease, or had had a clinical response to a 225-mg dose of ontamalimab in another study, TOSCA, a 12-week, open-label study in which ontamalimab was given to 39 patients with active Crohn disease who had previously received immunosuppressants. In OPERA, clinical response and remission were observed in greater proportions of patients in the treatment group than with placebo, although these differences hadn’t reached statistical significance, and in TOSCA, 80% of treated patients had a clinical response and 77% were in clinical remission at week 12.Conducted from July 2011 through July 2016 in 81 centers in 15 countries worldwide, OPERA-II examined safety (adverse events and serious adverse events) and efficacy (clinical remission and response rates at weeks 24 and 72, the rate of relapse and time to relapse, the proportions of patients with changes in dosage, and proportion who discontinued by week 16) outcomes in patients with moderate to severe Crohn with a history of failed immunosuppressant therapy. Participants received ontamalimab at 75 mg every 4 weeks for 72 weeks, and then were followed up every 4 weeks for 24 weeks. Dosage could be decreased to 22.5 mg for intolerance or adverse events or increased to 225 mg in patients with inadequate response.Overall, 149 of 268 patients completed the study; 74 patients discontinued during the study period and another 45 during follow-up. The most common event leading to discontinuation was disease flare, in 19.8% of patients; 2 patients died, no patients required dosage reductions, and 157 had dosage escalations. Median time to dosage escalation was 28 weeks. Of the 68 patients who required dosage escalation by week 8, 13 subsequently discontinued the study by week 16. During the treatment period, 249 patients reported a total of 1,550 adverse events, of which 385 were considered treatment related. During the follow-up period, 133 patients experienced a total of 461 adverse events, of which 42 were treatment related.Rates of clinical remission of Crohn disease, defined as a score on the Harvey Bradshaw index (HBI) less than or equal to 5, was 48.1% at baseline, 47.8% at the end of week 24 of follow-up, and 37.3% at week 72. Of the 128 patients who were not in remission at baseline, 84 achieved remission during the study, with a median time to remission of 16.9 weeks. Similar results were seen in response, as measured by decreases in HBI greater than or equal to 3 points; at baseline the response rate was 63.1%, at week 24 it was 54.5%, and by week 72 was 42.5%. Of the 99 patients who hadn’t demonstrated clinical response at baseline, 68 did so during the study, with a median time to response of 13.9 weeks. In those who received the higher, 225-mg dose, the proportion of those in remission remained relatively stable from week 12 (31.8%) to week 72 (32.2%). Relapse was defined as an increase greater than or equal to 3 points in HBI score from the lowest HBI score measured, with a total HBI score greater than or equal to 8. Of the 226 patients who had experienced clinical response at any time during the study, 119 (52.7%) experienced relapse, with the median time to relapse of 67.4 weeks. (D’Haens, G. R., et al. (2022). Long-term safety and efficacy of the anti-mucosal addressin cell adhesion molecule-1 monoclonal antibody ontamalimab (SHP647) for the treatment of Crohn’s disease: The OPERA II study. Inflamm Bowel Dis, 28(7), 1034–1044. Retrieved July 2022 from https://academic.oup.com/ibdjournal/article/28/7/1034/6357026#363711481)Released: August 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - July 2022
Lidocaine Infusions Relieve Pain in Chronic MigrainePatients with a particularly refractory form of chronic migraine who received a multiday continuous lidocaine infusion as part of aggressive inpatient treatment reported significant improvement in pain immediately following the infusion, and almost half of those who responded reported sustained relief at 1 month. This retrospective cohort study, published in Regional Anesthesia and Pain Medicine, analyzed medical records of patients with chronic migraine (at least 15 headache days/month for at least 3 months, in which at least 8 days meet criteria for migraine) refractory to outpatient treatment. These patients are treated in hospital with infusions of NSAIDs, corticosteroids, and neuroleptics, hoping to break the cycle of pain.READ MORE...Researchers examined the medical records of 609 hospital admissions from April 2017 to April 2020 at the Jefferson Inpatient Headache Unit in Philadelphia. This comprised 537 unique patients; 72 admissions were repeat admissions. Mean number of days between hospitalization for repeat admissions was 215.2 days. The mean age of the patients was 46, and 81% were female; all met criteria for refractory chronic migraine. The patients received continuous lidocaine infusions, starting at 1 mg/min and titrated to a maximum of 4 mg/min based on daily plasma levels, pain response, and tolerability. The infusions were planned for 5 to 7 days, although length differed based on clinical factors; for example, hospitalization and the infusion could be extended if the patient reported that the pain was slowly but steadily improving. The patients were otherwise be discharged from the hospital if they reported being pain-free for from 12 to 24 hours, or had a pain level that the patient felt allowed improved function, or if they experienced minimal response to treatment by hospital day 5. Mean duration of treatment was 5.2 days.Patients recorded pain intensity using a self-report Numerical Rating Scale, from 0 (pain-free) to 10 (worst pain imaginable); researchers measured change in that self-reported headache pain from baseline to discharge. At baseline and at postdischarge office visits (25 to 65 days after discharge), patients were also asked the number of headache days they had experienced during the previous 28 days, as well as current worst daily pain and average daily pain.A decline in median pain ratings was seen with lidocaine infusion: from 7.0 at baseline to 1.0 at discharge. Nearly 88% of patients showed a reduction in pain ratings by at least 2 points during the hospitalization period. These patients were labeled acute responders; of the 535 acute responders with available postdischarge data, 43.2% showed sustained improvements. Average pain remained below baseline at the postdischarge visit, with a median score of 5.5, and the patients reported fewer headache days in the previous month compared to baseline: 22.5 days vs. 26.8 days.The high acute responder rate is an encouraging finding, providing evidence of rapid relief for these patients. The waning of the effect seen over follow-up reflects the challenges presented by refractory chronic migraine. These results should offer support for design and implementation of randomized, controlled studies of lidocaine infusions to allow increased use of this treatment. Clinicians meanwhile can use these study results in their communications with patients, describing the likelihood of relief and the expected duration of that relief. (Shukla, D. (2022). Chronic migraine: Common anesthetic relieves pain in new study. Medical News Today. Retrieved June 2022 from https://www.medicalnewstoday.com/articles/chronic-migraine-common-anesthetic-relieves-pain-in-new-study; Schwenk, E. S., et al. (2022). Lidocaine infusions for refractory chronic migraine: A retrospective analysis. Region Anesth Pain Med, 47(7), 408–413. Retrieved June 2022 from https://rapm.bmj.com/content/47/7/408)Released: July 2022Nursing Drug Handbook© 2022 Wolters KluwerMaternal Vaccination for COVID-19 Offers Some Protection for Their InfantsVaccination against SARS-CoV2 during pregnancy is known to result in detectable maternal antibodies to the virus in cord blood, human milk, and serum specimens from infants, but it’s unknown how this fact correlates with protection against COVID-19 in infants under age 6 months, who are at high risk for complications of COVID-19 but aren’t eligible for vaccination. A case-control study published in the New England Journal of Medicine assessed the effectiveness of full maternal vaccination (that is, two doses of an mRNA SARS-CoV2 vaccine) against hospitalization for COVID-19 in infants younger than age 6 months. Between July 2021 and March 2022, the study enrolled infants hospitalized for COVID-19 (case infants; n = 537) and matched them with hospitalized infants who didn’t have COVID-19 (control infants; n = 521) at 30 hospitals across 22 U.S. states. Median age of infants was 2 months; 19% of case infants and 24% of control infants had at least one underlying health condition. All case infants were identified with COVID-19 as the primary reason for their admission or with a clinical syndrome consistent with acute COVID-19 who then tested positive on a SARS-CoV2 PCR test; control infants were hospitalized for other reasons and tested negative on a PCR test. Researchers attempted to enroll a control infant for every case infant, with a date of hospital admission that was within 4 weeks of the admission date of the case infants.READ MORE...The overall effectiveness of maternal vaccination against COVID-associated hospitalization in their infants age 6 months and younger was 52%; its effectiveness against intensive care unit admission was 70%. Among case infants, 113 (21%) required intensive care treatment for COVID-19, including 64 (12%) who required mechanical ventilation or vasoactive infusions. Two infants died and two required ECMO treatment; none of these four infants was born to fully vaccinated mothers.The study examined appropriate timing of maternal vaccination to facilitate the greatest transfer of maternal antibodies. In this study, effectiveness at preventing hospitalization was 69% when vaccinated after 20 weeks of pregnancy and 38% when the last vaccination was given during the first 20 weeks of pregnancy. The researchers were also able to examine results during the period of the circulation of the delta and omicron variants of the virus. Of the 537 case infants, 181 were admitted during the delta circulation period and 356 during the omicron circulation period. The effectiveness of the maternal vaccination against COVID-19 hospitalization was 80% during the delta period and 38% during the omicron period.These data support the safety of COVID-19 vaccination during pregnancy. The CDC recommends vaccination, including boosters, for pregnant people. Despite the known benefits and safety of the mRNA vaccine, vaccination rates during pregnancy still lag: only 71% of pregnant people in the United States were fully vaccinated, with an even lower rate among non-Hispanic Black people (58%). (Halasa, N. B., et al. (2022). Maternal vaccination and risk of hospitalization for Covid-19 among infants. New Engl J Med, 387, 109–119. Retrieved June 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2204399?query=featured_coronavirus; Rasmussen, S. A., & Jamieson, D. J. (2022). Covid-19 vaccination during pregnancy—Two for the price of one. New Engl J Med, 387, 178–179. Retrieved June 2022 from https://www.nejm.org/doi/full/10.1056/NEJMe2206730?query=recirc_curatedRelated_article)Released: July 2022Nursing Drug Handbook© 2022 Wolters KluwerNewer P2Y12 Inhibitors Improve Mortality in Patients with MI Complicated by Cardiac Arrest or Cardiogenic ShockManagement of acute myocardial infarction (MI) complicated by cardiac arrest or cardiogenic shock is challenging, and current treatment is less successful in these patients. A review and meta-analysis published in Mayo Clinic Proceedings offers evidence that “newer” P2Y12 receptor inhibitors should be preferred when treating this high-risk population.READ MORE...Current treatment of acute MI complicated by cardiac arrest or cardiogenic shock includes percutaneous coronary intervention followed by use of dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor. Clopidogrel, the first P2Y12 inhibitor on the market, has been the standard of care; this study examined results of trials that compared outcomes with other P2Y12 inhibitors ticagrelor and prasugrel vs. clopidogrel.Because the large sample sizes seen in other studies of MI are not possible for these conditions, the review identified only eight studies, seven of them cohort studies. The studies comprised 1100 patients; 695 patients (63.2%) received clopidogrel and 405 patients (36.8%) received the newer P2Y12 inhibitors ticagrelor or prasugrel. They compared outcomes: early mortality, either in-hospital or 30-day all-cause mortality; 1-year, all-cause mortality; and the incidence of major bleeding and stent thrombosis.The “newer” P2Y12 cohort (prasugrel and ticagrelor) had lower rates of early mortality (odds ratio [OR], 0.60) and of 1-year mortality (OR, 0.51). The analysis did not find a significant difference in major bleeding (OR, 1.21) or in stent thrombosis (OR, 2.01) with use of ticagrelor or prasugrel, although there were numerically more bleeding events with the “newer” drugs.The study is limited by the retrospective, observational character of most of the studies involved; there is the risk that selection bias comes into play, as clinicians determine that certain patients would benefit from the more potent newer P2Y12 receptor inhibitors. In addition, it would be valuable to design a study that examined these complications separately, recognizing that cardiac arrest and cardiogenic shock have different effects on, for example, perfusion of other organs. (Patlolla, S. H., et al. (2022). Newer P2Y12 inhibitors vs clopidogrel in acute myocardial infarction with cardiac arrest or cardiogenic shock: A systematic review and meta-analysis. Mayo Clin Proceed, 97(6), 1074–1085. Retrieved June 2022 from https://www.mayoclinicproceedings.org/article/S0025-6196(22)00120-3/fulltext; Effron, M. B. (2022). Importance of more potent antiplatelet therapy in myocardial infarction with cardiac arrest or cardiogenic shock. Mayo Clin Proceed, 97(6), 1041–1043. Retrieved June 2022 from https://www.mayoclinicproceedings.org/article/S0025-6196(22)00255-5/fulltext)Released: July 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - June 2022
Mepolizumab a Good Choice in Chronic Rhinosinusitis with Comorbid AsthmaResults of the phase III SYNAPSE study demonstrated the effectiveness of mepolizumab in reducing nasal polyp size and nasal obstruction in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Mepolizumab is an MAb that prevents interleukin-5 from binding to its receptors on eosinophils, thus selectively inhibiting eosinophilic inflammation. The burden of disease in CRSwNP is greatest among those with comorbid asthma or aspirin-exacerbated respiratory disease (AERD) and in patients with eosinophilic infiltration. The researchers conducted a subgroup analysis targeting those patients that suggests that mepolizumab should be the treatment choice in CRSwNP in patients with comorbid asthma or AERD.READ MORE...SYNAPSE was a randomized, double-blind, 52-week study in patients with severe bilateral CRSwNP eligible for surgery despite intranasal corticosteroid treatment. Enrolled patients received subcutaneous mepolizumab 100 mg or placebo every 4 weeks plus standard of care (daily mometasone furoate nasal spray, saline nasal irrigations, and short courses of steroids or antibiotics, as needed) for 52 weeks. The patients had recurrent bilateral nasal polyps. The study reported the proportion of patients with greater than or equal to 1-point increase in total endoscopic nasal polyp score at week 52 and greater than or equal to 3-point improvement in nasal obstruction visual analog (VAS) score by weeks 49 to 52. Endoscopic nasal polyp score ranges from 0 (no polyps) to 4 (large polyps causing complete obstruction of inferior meatus) for each nostril, for a highest possible total score of 8. The nasal obstruction VAS score ranges from 0 to 10. This subgroup analysis included 407 patients; 289 had comorbid asthma, 108 had comorbid AERD, 371 had blood eosinophil cell (BEC) counts greater than or equal to 150 cells/f mm3, and 278 had BEC counts greater than or equal to 300 cells/f mm3.In the intent-to-treat population, more patients who received mepolizumab had greater than or equal to 1-point improvement from baseline in endoscopic nasal polyp score—50.5% of patients vs. 28.4% in the placebo group. The proportions of patients with greater than or equal to 1-point improvement in endoscopic nasal polyp score was higher across the various subgroups with mepolizumab vs. placebo:· Comorbid asthma: 52.9% vs. 29.5%· Comorbid AERD: 51.1% vs. 20.6%· BEC count greater than or equal to 150 cells/f mm3: 49.5% vs. 28.1%· BEC count greater than or equal to 300 cells/f mm3: 50.4% vs. 28.1%The proportion of patients who had a greater than or equal to 3-point improvement in nasal obstruction VAS score also differed greatly across these subgroups:· Comorbid asthma: 60.0% vs. 34.9%· Comorbid AERD: 64.4% vs. 30.2%· BEC count greater than or equal to 150 cells/f mm3: 59.1% vs. 34.1%· BEC count greater than or equal to 300 cells/f mm3: 59.0% vs. 32.4%Among the other findings is that patients receiving mepolizumab had a lower risk of surgery than those receiving placebo. This reduction was greater in patients without asthma than those with asthma but was similar irrespective of the presence of AERD. This benefit may be an important consideration for patients who express concern over the risks associated with surgery. (Bachert, C., et al. (2022). Mepolizumab for chronic rhinosinusitis with nasal polyps: Treatment efficacy by comorbidity and blood eosinophil count. J Allergy Clin Immunol, 149(5), 1711-1721.E6.Retrieved June 2022 from https://www.jacionline.org/article/S0091-6749(22)00001-X/fulltext#fx1)Released: June 2022Nursing Drug Handbook© 2022 Wolters KluwerOral Antivirals for COVID-19The best tool health care providers have to combat spread of COVID-19 disease is the vaccine program targeting the virus. However, research into treatments to mitigate the effects of the virus after infection are ongoing. In December 2021 two oral antiviral treatments were made available under an Emergency Use Authorization (EUA): ritonavir-boosted nirmatrelvir and molnupiravir.READ MORE...The Centers for Disease Control and Prevention has issued a health advisory with updates on the availability of and use of these treatments for mild to moderate COVID-19. When theseagents were first made available, ensuring adequate supplies to keep up with demand was challenging due to the rapid increase in omicron variant cases of COVID-19. These treatments are growing in importance as that highly transmissible variant continues as the predominant strain, with new subvariants emerging, and as mitigation strategies such as masking and social distancing are being phased out. The FDA has ensured that oral antivirals are widely available and can be accessed with a provider prescription at pharmacies and at Test-to-Treat locations.Both ritonavir-boosted nirmatrelvir and molnupiravir work best early in the course of illness before SARS-CoV2 can have a chance to replicate and do damage. They are authorized for use within 5 days of symptom onset in nonhospitalized patients who have tested positive for SARS-CoV2 and are at high risk. High-risk patients include those over age 65 or those older than age 12 with an underlying condition that increases the risk of severe outcomes of COVID-19, such as cancer, heart disease, diabetes, and obesity. The preferred therapies are the oral antiviral ritonavir-boosted nirmatrelvir and the infusion remdesivir. The alternatives, molnupiravir and the monoclonal antibody bebtelovimab (available under EUA since February 2022) are to be used only when the preferred treatments are unavailable, not feasible, or not appropriate. Ritonavir-boosted nirmatrelvir produced an 89% reduction in the risk of hospitalization and death; molnupiravir is less efficacious, producing a 30% reduction in risk. There are numerous considerations that come into play when deciding on which oral antiviral to use. Ritonavir-boosted nirmatrelvir should be avoided by those with severe kidney or liver disease; in addition, because ritonavir acts to boost levels of nirmatrelvir by slowing down hepatic metabolism of the other drug through inhibition of CYP3A4, its use should be avoided with other drugs highly dependent on CYP3A enzymes for clearance. Its use should also be avoided with use of CYP3A inducers, which can result in low levels of ritonavir and therefore loss of virologic response. Molnupiravir use should be avoided in those who are, or are attempting to become, pregnant and in those under age 18; men with sexual contact with women of childbearing age should use a reliable method of contraception during molnupiravir treatment and for 3 months afterward.In the battle against the pandemic, health care providers and their patients should be doing everything they can to avoid COVID-19 disease and disease progression in patients with risk factors: vaccinations, testing, isolation when positive, and these antiviral treatments. Providers should educate their patients at high risk not to overlook mild cases and to remember that accurate testing remains key to COVID-19 prevention. (Petty, L. A., & Malani, P. N. (2022). Oral antiviral medications for COVID-19. JAMA Patient Page. Retrieved June 2022 from https://jamanetwork.com/journals/jama/fullarticle/2791780#:~:text=Two%20new%20oral%20antiviral,US%20under%20emergency%20use%20authorization;Katella, K. (2022).13 things to know about Paxlovid, the latest COVID-19 pill. Yale Medicine. Retrieved June 2022 from https://www.yalemedicine.org/news/13-things-to-know-paxlovid-covid-19; U.S. Food & Drug Administration. (2021, December 22). Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. [Press Release]. Retrieved June 2022 from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19;Centers for Disease Control and Prevention. (2022, April 25). Updated information on availability and use of treatments for outpatients with mild to moderate COVID-19 who are at increased risk for severe outcomes of COVID-19. [Press release]. Retrieved June 2022 from https://emergency.cdc.gov/han/2022/han00463.asp;National Institutes of Health. COVID-19 Treatment Guidelines. (2022). Ritonavir-boosted nirmatrelvir (Paxlovid). Retrieved June 2022 from https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ritonavir-boosted-nirmatrelvir--paxlovid-/)Released: June 2022Nursing Drug Handbook© 2022 Wolters KluwerPolypharmacy and Disability in Older AdultsA new Japanese study published in Geriatrics and Gerontology International evaluated the relationship between high-risk prescribing practices and the risk for disability in people age 65 and older. These practices include polypharmacy (the use of five or more prescription drugs) and the use of drugs with sedative or anticholinergic properties, including antipsychotics, benzodiazepines, and antiparkinsonian drugs. These prescribing practices have been previously shown to be associated with physical frailty among older adults.READ MORE...The researchers for the University of Tsukuba conducted a population-based, case-control study, the study cohort nested within a cohort of older adults in a Japanese city. Using combined medical claims and long-term care (LTC) needs certification database, researchers identified 2,123 individuals who received a first LTC needs certification and matched them to 40,295 controls (accounting for 89% of the over-65 population) based on age, sex, residence, and the observation period. In Japan, people age 65 and older with a functional disability are eligible for LTC services; an LTC needs certification is needed to access these services, so the researchers were able to use it as a proxy for disability.The study demonstrated a dose-response relationship between both polypharmacy and the use of drugs with sedative or anticholinergic properties with the risk for LTC needs certification. Adjusted odds ratios (OR) of this outcome were as follows:· Polypharmacy (5 to 9 prescription drugs): OR, 1.32· Hyperpolypharmacy (greater than or equal to 10 prescription drugs): OR, 1.87· Cumulative doses of drugs with sedative or anticholinergic properties, in terms of defined daily dose:o defined daily dose 1–364: OR, 1.07o defined daily dose 365–729: OR, 1.25o defined daily dose greater than 730: OR, 1.33Further study should examine whether adjusting prescribing patterns in these patients could reduce the risk of LTC needs certification in older adults and reduce the LTC burden for the public. (University of Tsukuba. (2022, May 18). Potential pitfalls of high-risk prescribing practices in older adults. AlphaGalileo. Retrieved June 2022 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/221191?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/221191;Kuroda, N., et al. (2022). Associations of polypharmacy and drugs with sedative or anticholinergic properties with the risk of long-term care needs certification among older adults in Japan: A population-based, nested case–control study. Geriatr Gerontol Int. Advanced online publication. Retrieved June 2022 from https://onlinelibrary.wiley.com/doi/full/10.1111/ggi.14393)Released: June 2022Nursing Drug Handbook© 2022 Wolters KluwerRisdiplam Effective Long-Term for Spinal Muscular AtrophyGenentech presented long-term data from the FIREFISH study, including one-year data for the open-label extension, at the European Paediatric Neurology Society Conference, held April 28 through May 2, 2022. FIREFISH is a phase II/III, 2-part, multicenter trial that examined the long-term efficacy and safety of risdiplam in infants with symptomatic Type 1 spinal muscular atrophy (SMA). SMA is a group of severe, progressive neuromuscular diseases that is the leading cause of infant mortality. It’s caused by a mutation of the SMN1 gene that leads to a deficiency of the SMN protein, resulting in cellular imbalance in motor neurons that in turn causes the motor neuron endplates to not properly connect to muscle and leads to death of the motor neurons. Without treatment, depending on the type of SMA, the patients can lose physical strength; and the ability to walk, eat, or breathe can be significantly diminished or lost. Untreated infants with type 1 SMA typically don’t survive past age 2. Risdiplam is a survival motor neuron 2 splicing modifier that allows production of full-length SMN protein and thereby can affect the progression of SAM.READ MORE...The original study evaluated efficacy and safety in infants ages 1 to 7 months at the time of trial enrollment. Part 1 of the trial was a dose-finding study; in part 2, the patients received liquid risdiplam orally or via feeding tube once daily. After 24 months, the trial entered a 3-year open-extension phase. At 36 months after trial enrollment, 91% (n = 58) of children treated with risdiplam were alive. The marker chosen to demonstrate efficacy was the percentage of children able to sit without support for 5 seconds, as assessed by the Bayley Scale of Infant Development at month 12. Without treatment, infants with type 1 SMA are never able to sit without support. At this 36-month follow-up, among the 48 children who could be assessed, 32 maintained that ability and 4 gained it between months 24 and 36, and no child who had gained the ability to sit without support for 5 seconds lost that ability. Further, 20 children maintained and 15 gained the ability to sit without support for at least 30 seconds. The children had other successes in the improvement or maintenance of skills measured on the Hammersmith Infant Neurological Examination between 24 and 36 months on treatment:· Ability to hold head up: 36 maintained, 3 gained, 0 lost this ability· Pivot while sitting: 15 maintained, 11 gained, 0 lost this ability· Stand with support: 6 maintained, 5 gained, 1 lost this ability· Walk while holding on: 1 maintained, 2 gained, 0 lost this abilityThe study showed overall continued reduction in serious adverse events and hospitalization over time. The rate of serious adverse events decreased by approximately 50% after each 12-month treatment period and a 78% reduction between the first and third year of treatment. The rate of hospitalization decreased from 1.24 per patient per year over 12 months to 0.70 hospitalizations per patient per year over 36 months. (Genentech. (2022, April 28). New three-year data for Genentech’s Evrysdi (risdiplam) show long-term improvements in survival and motor milestones in babies with type 1 spinal muscular atrophy (SMA). [Press Release]. Retrieved June 2022 from https://www.gene.com/media/press-releases/14950/2022-04-28/new-three-year-data-for-genentechs-evrys)Released: June 2022Nursing Drug Handbook© 2022 Wolters Kluwer
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