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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 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer

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 2023
Nursing Drug Handbook

© 2023 Wolters Kluwer

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 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer