Lippincott ^® NursingCenter ^®

The study enrolled 3,017,352 health plan members, using data from three commercial claims databases after administration of the BNT162b2 COVID-19 vaccine (5,901,825 doses). It included persons ages 5 to 17 who received the vaccine from the earliest dates of its Emergency Use Authorization through June 2022 and divided the study population into three age groups: ages 5 to 11, 12 to 15, and 16 to 17. Conducted under the FDA's public health surveillance mandate, the study used a near-real-time monitoring framework that enables early detection of potential safety signals, including rare outcomes that may not be identified in other trials.

They conducted monthly sequential testing and generated incidence rate ratios of observed outcome rates compared with expected rates. The health outcomes the study monitored for included cardiac outcomes, including myocarditis/pericarditis and MI; thrombotic complications, including deep vein thrombosis and stroke; neurologic reactions such as Guillain-Barré and other reactions, including anaphylaxis

Only myocarditis/pericarditis met the statistical threshold for safety after vaccination. Safety signal was observed after the primary series of vaccines in all three databases for age groups 12 to 15 and 16 to 17. In dose-specific analysis, it was detected after dose 2 in these age groups. There was no evidence of this outcome in the youngest age group (ages 5 to 11 years). Of the 153 cases of myocarditis/pericarditis that this monitoring found, medical records review was conducted on 37 cases. Of these, 73.0% (n = 27) were confirmed as myocarditis/pericarditis, of whom 25 were male; 19 patients were hospitalized for it, with a mean length of stay of 2.8 days.

These results provide reassuring real-world evidence of vaccine safety. They also provide evidence in support of reports in peer-reviewed journals that suggested increased risk for myocarditis/pericarditis with mRNA vaccines, especially among young males. It's still a very rare event, with an average incidence of 39.4 cases per million doses administered to children ages 5 to 17. (Hu, M., et al. (2023). Safety of the BNT162b2 COVID-19 vaccine in children aged 5 to 17 years. JAMA Pediatr, 177(7), 710–717. Retrieved July 2023 from https://jamanetwork.com/journals/jamapediatrics/fullarticle/2805184

Released: August 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

By starting treatment earlier, the study shows, patients may be able to prevent or minimize further damage. Those in the earliest treatment group had a 45% lower risk of disability progression to a score of 3 on the 10-point Expanded Disability Status Score (EDSS) by the end of the study compared to those treated latest. A score of 3 on the EDSS reflects a patient who can walk unassisted but has either moderate disability in one of eight areas (muscle weakness, balance and coordination, speech and swallowing, numbness, bowel and bladder function, visual function, thinking skills) or mild disability in three or four of those eight areas. In addition, those in the earliest treatment group were 60% less likely to progress to secondary progressive MS compared with those who began treatment latest. Those treated earliest were also 50% more likely to remain stable a year after initial treatment than those in the latest treatment group.

Previous studies haven't integrated magnetic resonance (MR) findings when evaluating outcomes. To confirm the role of MR findings in treatment decisions, researchers in this study also determined the time elapsed from the first demyelinating event to treatment initiation in all patients with available radiologic information. A 5-point MRS was determined, according to the sum of these indications:

• more than 9 brain lesions (1 point)
• at least 1 infratentorial lesion (1 point)
• at least 1 spinal cord lesion (1 point)
• at least 1 contrast-enhancing brain lesion (1 point)
• at least 1 contrast-enhancing spinal cord lesion (1 point).

They found a 62.4% reduction in median time between the first demyelinating event and the first ever treatment initiation from patients with an MRS of 5 versus an MRS of 1.

 

This study contributes to the understanding of how treating MS at different stages affects disability and can improve treatment strategies as well as the patient's quality of life. (Lennon, A. (2023). Multiple sclerosis: Early treatment may slow disease progression. Med News Today. Retrieved July 2023 from https://www.medicalnewstoday.com/articles/starting-treatment-at-first-sign-of-ms-symptoms-could-slow-down-progression; Cobo-Calvo, A., et al. (2023). Association of very early treatment initiation with the risk of long-term disability in patients with a first demyelinating event. Neurology, 10, Article 207664. Retrieved July 2023 from https://n.neurology.org/content/early/2023/07/19/WNL.0000000000207664)

Released: August 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

The retrospective study analyzed data from COREA-AMI, a nationwide PCI registry, collected from consecutive admissions for MI at tertiary care hospitals in Korea from January to August 2014. All patients underwent PCI within 48 hours after admission; then were prescribed dual antiplatelet therapy (100 mg of aspirin plus a P2Y12 inhibitor, either 75 mg clopidogrel, 10 mg prasugrel, or 90 mg ticagrelor b.i.d.) for at least 1 year. The patients received further therapy, including statins, beta blockers, and renin-angiotensin-aldosterone inhibitors, according to guidelines. The most widely used beta blockers were carvedilol (52.7%), bisoprolol (35.2%), and nebivolol (9.0%). The 7,159 patients enrolled were event-free for 3 months after MI; patients were divided into four groups according to the duration of beta blocker use; less than 12 months (n = 1,729), 12 to less than 24 months (n = 809), 24 to less than 36 months (n = 864), and greater than or equal to 36 months (n = 3,757). The study compared the clinical benefits of beta blocker maintenance use stratified by duration of use, examining for a composite outcome of all-cause death, recurrent MI, heart failure, or hospitalization for unstable angina. In addition, researchers specifically evaluated the efficacy of beta blocker use beyond 36 months.

During the mean 5 years of follow-up, 1,788 primary outcomes occurred (in 25% of patients overall), including these components:

• 1,112 all-cause deaths
• 333 recurrent MIs
• 175 cases of heart failure
• 695 hospitalizations for unstable angina.

In addition, 805 cardiac deaths were seen in the overall population of patients. Significant stepwise decreases in the incident rate of three outcomes were seen.

 

• The composite outcome occurred in:
  • 34.1% of patients using beta blockers for less than 12 months (n = 590/1,729)
  • 33.6% of patients using beta blockers for 12 to less than 24 months (n = 272/809)
  • 29.3% of patients using beta blockers for 24 to less than 36 months (n = 253/864)
  • 17.9% of patients using beta blockers for greater than or equal to 36 months (n = 673/3,757)
• All-cause death occurred in:
  • 26.7% of patients using beta blockers for less than 12 months (n = 461/1,729)
  • 24.8% of patients using beta blockers for 12 to less than 24 months (n = 201/809)
  • 19.9% of patients using beta blockers for 24 to less than 36 months (n = 172/864)
  • 7.4% of patients using beta blockers for greater than or equal to 36 months (n = 278/3,757)
• Cardiac death occurred in:
  • 20.5% of patients using beta blockers for less than 12 months (n = 354/1,729)
  • 17.3% of patients using beta blockers for 12 to less than 24 months (n = 140/809)
  • 14.0% of patients using beta blockers for 24 to less than 36 months (n = 121/864)
  • 5.1% of patients using beta blockers for greater than or equal to 36 months (n = 190/3,757).

 

More than half (52.5%) of patients continued beta blocker treatment for longer than 36 months. In the 3-year landmark analysis of 5,918 patients who remained event-free for 36 months, the 2,593 patients who received beta blocker treatment for less than 36 months exhibited considerably higher risks, not only of the primary composite outcome (adjusted hazard ratio [HR], 1.59), but also of all-cause death (adjusted HR, 1.88), cardiac death (adjusted HR, 2.25), recurrent MI (adjusted HR, 1.57), and heart failure (adjusted HR, 1.95), compared to those using beta blockers for greater than or equal to 36 months.

These results have clinical implications regarding the efficacy of long-term maintenance therapy after reperfusion. Further trials can help determine the optimal duration of such maintenance. (Abbott, J. D., & Goldberger, J. J. (2023). β-blocker therapy after myocardial infarction: A little goes a long way. J Am Heart Assoc, 12(15), Article e030867. Retrieved July 2023 from https://www.ahajournals.org/doi/10.1161/JAHA.123.030867; Lee, M., et al. (2023). Comparative effectiveness of long-term maintenance beta-blocker therapy after acute myocardial infarction in stable, optimally treated patients undergoing percutaneous coronary intervention. J Am Heart Assoc, 12(15), Article e028976. Retrieved July 2023 from https://www.ahajournals.org/doi/10.1161/JAHA.122.028976)

Released: August 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer

The study included two phase 3 double-blind, placebo-controlled trials totaling 52 weeks of treatment. Lucent-1 lasted 12 weeks and enrolled 1,162 adults with moderately to severely active ulcerative colitis; 868 patients were randomly assigned to mirikizumab 300 mg IV every 4 weeks for 12 weeks and 294 patients to placebo. Lucent-2, the maintenance phase, enrolled 544 responders to Lucent-1 (365 from the mirikizumab group and 179 from the placebo group), who were then rerandomized 2:1 to mirikizumab 200 mg subcutaneous every 4 weeks for 40 weeks or placebo. Patients who didn't respond to either arm of the induction trial (Lucent-1) received open-label extended induction treatment with an additional 3 doses of mirikizumab IV every 4 weeks for an additional 12 weeks. If they responded to that extended trial, they were added to the cohort for the maintenance trial; if there was no response after this extended induction, the patients were withdrawn from the trial.

Researchers determined clinical remission at week 12 in Lucent-1 and at week 40 (52 weeks overall) in Lucent-2. They also examined the patients for clinical response, endoscopic remission, and increase in bowel-movement urgency. The severity of ulcerative colitis was assessed by means of a modified Mayo score (scale, 0 to 9); those enrolled in the study had a score from 4 to 9, with an endoscopic subscore (range, 0 to 3) of 2 to 3. Clinical remission was defined as 0 on the stool-frequency subscore, or a stool-frequency subscore of 1 with a decrease of at least 1 point from baseline, a rectal-bleeding subscore of 0, and an endoscopic subscore of 0 to 1.

Mirikizumab was shown to be more effective than placebo both in inducing and maintaining clinical remission in patients with ulcerative colitis. Significant differences were seen in clinical response, endoscopic remission, and bowel-movement urgency than with placebo. A significantly higher percentage of patients in the mirikizumab group than the placebo group had clinical remission at week 12 of the induction trial (Lucent-1): 24.2% versus 13.3% (difference, 11.1 percentage points) and at week 40 of the maintenance trial (Lucent-2): 49.9% versus 25.1% (difference, 23.2 percentage points). Results also favored the mirikizumab group for the major secondary endpoints of clinical response, remission of symptoms at weeks 4 and 12, clinical response in patients who had previous treatment failures, and histologic-endoscopic mucosal improvement. Among the 272 patients in the open-label induction extension, 53.7% had clinical response and 11.4% had clinical remission by week 12; of the 144 patients in this group who went on to receive mirikizumab in the maintenance trial, clinical remission was maintained in 72.2%. Overall incidence of adverse events was similar in the mirikizumab and placebo groups during both phases of the trial, although nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1,217 patients treated with mirikizumab at any time during the two Lucent trials, 15 experienced an opportunistic infection, including 6 with herpes zoster, and 8 had cancer, including 3 with colorectal cancer; among those receiving placebo, 1 had herpes zoster and none had cancer.

This report presents another option for people with ulcerative colitis, especially those who didn't respond to other medications. Longer trials are ongoing to assess more prolonged efficacy and safety of mirikizumab in ulcerative colitis. (D'Haens, G., et al. (2023). Mirikizumab as induction and maintenance therapy for ulcerative colitis. New Engl J Med, 388, 2444–2455. Retrieved July 2023 from https://www.nejm.org/doi/full/10.1056/NEJMoa2207940; Bailey, E. (2023). New drug mirikizumab shows promise in ulcerative colitis remission. Medical News Today. Retrieved July 2023 from https://www.medicalnewstoday.com/articles/new-drug-mirikizumab-shows-promise-in-ulcerative-colitis-remission)

Released: August 2023

Nursing Drug Handbook

© 2023 Wolters Kluwer