Bimekizumab Efficacy for Psoriasis Persists Long-Term
Bimekizumab produces dual inhibition of interleukin-17A and -17F (IL-17A/F). BE RADIANT, a phase 3b, randomized clinical trial, showed that such dual inhibition with bimekizumab was superior to IL-17A inhibition alone with secukinumab. In the open-label extension of BE RADIANT, in which all patients received bimekizumab, the high levels of clinical response seen through the first 48 weeks of treatment were generally sustained through 96 weeks.
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In BE RADIANT, patients received bimekizumab (320 mg every 4 weeks or every 8 weeks) or secukinumab (300 mg weekly to week 4, then every 4 weeks). Results from Year 1 showed that bimekizumab produced high rates of complete skin clearance (100% improvement on the Psoriasis Area and Severity Index, or PASI 100). At baseline, 743 patients were randomized to bimekizumab (n = 373) or secukinumab (n = 370); of those, 336 (90.1%) and 318 (85.9%), respectively, entered the open-label extension. They were randomized as follows:
- All patients who had not achieved PASI 90 by week 48 were assigned to receive bimekizumab every 4 weeks.
- Those who had achieved PASI 90 on an every-8-week schedule continued receiving bimekizumab on that schedule.
- Those who had achieved PASI 90 on an every-4-week schedule or on secukinumab were randomized to receive bimekizumab on either schedule; at week 64, when phase 3 data demonstrated similar efficacy for the two schedules, those still receiving the drug on an every-4-week schedule were switched to every 8 weeks.
At week 48, more patients had achieved complete skin clearance (PASI 100) with bimekizumab than secukinumab (74.8% versus 52.8%). The proportions of patients with PASI 100 responses were maintained to week 96 in patients who had continuously received bimekizumab (70.8%), and the proportion increased in patients who switched from secukinumab to bimekizumab (76.6%). Results were consistent for patients who received bimekizumab by either schedule. Improvements on other measures were also sustained in patients receiving continuous bimekizumab and improved in those who switched from secukinumab at week 48. For example, the proportions of patients achieving improvements in at least two categories from baseline in the Investigator's Global Assessment were 94.0% with bimekizumab at week 48 and 90.9% at week 96, and 85.1% with secukinumab at week 48, improving to 90.7% in those who switched to bimekizumab. In addition, the proportions of patients achieving clear skin so that less than 1% of BSA was affected by psoriasis at week 48 for bimekizumab was 88.4%, maintained at week 96 in 86.9%, and 75.9% at week 48 for secukinumab, rising to 87.4% at week 96 in those who switched to bimekizumab.
Adverse effects on the open-label extension generally decreased or stayed consistent relative to 1-year data. The most common adverse events were nasopharyngitis, oral candidiasis, and UTI. Despite the expected increased risk of oral candidiasis with dual therapy against IL-17A/F, most cases were mild or moderate. Only one complex case of systemic candidiasis was seen. Note that the 2-year safety data includes a greater proportion of patients receiving every-8- week dosing than in Year 1. (Strober, B., et al. (2023). Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: Two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial. J Am Acad Dermatol. 2023; 89(3), 486–495. Retrieved October 2023 from https://www.jaad.org/article/S0190-9622(23)00782-X/fulltext
Released: September 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
How Did the COVID-19 Pandemic Affect Adherence to Psychotropic Medications?
The COVID-19 pandemic and associated public health measures shifted the ways people accessed health care. Canadian public health measures in response to the pandemic included social distancing, travel bans, reduced physical contact, and restrictions on nonessential services. A retrospective, population-wide observational cohort study, conducted at the Manitoba Center for Health Policy, looked to determine the effects of the challenges posed by the pandemic, from difficulty getting to pharmacies and clinics to overall supply chain problems, on adherence rates for various psychotropic medications.
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The researchers hypothesized that the proportion of patients achieving a medication possession ratio (MPR) of at least 80% (0.80) would decrease compared to expected, and that the rates of drug discontinuation would increase. MPR, the most used measure of adherence involving administrative data, is calculated by determining the days' supply for all fills of a given medication prescription and dividing it by the number of days in the same period. The study monitored adherence for the last three quarters of 2019 and all of 2020 and compared the magnitude of change in adherence in each quarter in 2020 to the previous quarter and to its respective quarter in 2019. In addition, quarterly discontinuation rates were determined by counting those who had good adherence in the preceding two quarters who then failed to fill their prescription.
As expected with the implementation of the public health measures to combat the pandemic in 2020-Q2, antidepressant adherence was lower in that quarter compared to the previous quarter. But they rebounded in Q3 and Q4, surpassing the adherence rates of the previous year. Compared with the expected trend, the proportion of individuals adherent to antidepressants and stimulants increased in 2020-Q4 and of anxiolytics and cannabinoids in 2020-Q3. The difference in adherence rates for antidepressants in 2020-Q4 was approximately twofold higher than expected (2.27). Adherence to anxiolytics was 1.39 times greater than expected in 2020-Q3. The proportion of individuals adherent to stimulants decreased in 2020-Q3 (−3.28), and no changes were observed for adherence to antipsychotics.
All drug classes except lithium showed decreases in drug discontinuation during the pandemic compared to 2019, possibly due to the increased mental health burden brought on by the pandemic causing a reluctance to discontinue psychotropic medications. The odds of discontinuing antidepressants in each quarter of 2020 were compared to the respective quarter in 2019; odds ratios (ORs) were 0.81, 0.88, and 0.86 for Q2, Q3, and Q4, respectively. This was also true for anxiolytics/sedative-hypnotics, with ORs of 0.85, 0.86, and 0.90 for Q2, Q3, and Q4, respectively. For cannabinoids, the odds of discontinuing were lower in two quarters of 2020: OR, 0.53 and 0.62 for Q2 and Q3, respectively, and the odds of discontinuing stimulants was lower in Q2 and Q4 of 2020 compared with 2019, with ORs of 0.92 and 0.74, respectively.
By the time of the second wave of COVID-19 that was predominant in the final quarter of 2020, patients had adjusted. Although accessing in-person clinics was still restricted, patients were able to access medication during the pandemic. Further study of the impact of the pandemic on adherence long-term and in differences in access for specific populations, such as urban or rural populations, is ongoing. In addition, it will be necessary to determine whether the higher adherence to certain medications will have an impact on future health service use and long-term outcome. (Froese, B., et al. (2023). Adherence to psychotropic medication before and during COVID-19: A population-wide retrospective observational study J Clin Psychopharmacol, 43(4), 313–319. Retrieved October 2023 from https://journals.lww.com/psychopharmacology/fulltext/2023/07000/adherence_to_psychotropic_medication_before_and.3.aspx
Released: September 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer
Proton Pump Inhibitor Use and the Risk of Dementia
Proton pump inhibitors (PPIs; lansoprazole, omeprazole, pantoprazole, rabeprazole, esomeprazole), available by prescription and OTC, are currently a first-line option for short-term treatment (4 to 8 weeks) of gastroesophageal reflux disease and peptic ulcers. Although they have not been approved for longer-term use, such use is still common; long-term use of PPIs has been linked to numerous health conditions, including stroke, CV disease, chronic kidney disease, and dementia. Studies on the links between PPI use and the risk of dementia have produced mixed results, with little information on the effects of cumulative use.
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Using data from the Atherosclerosis Risk in Communities (ARIC) study, a community-based cohort, from the time of enrollment (1987 to 1989) through 2017, a trial published in Neurology demonstrated a significantly higher risk of dementia in patients who used PPIs for more than 4½ years. The ARIC cohort originally numbered 15,792; participants attended multiple in-person visits over the years. Visit 5, which occurred between 2011 and 2013 and was attended by 6,538 participants, was the first in which PPI use was common. Analysis, using Visit 5 as baseline, included 5,712 participants who were dementia-free at that point. To track medication use, participants were asked to bring to in-person clinic visits all OTC and prescription medications they had taken in the previous 2 weeks or to report that same information on annual phone calls.
Current PPI use was defined as actively using the drugs at Visit 5; cumulative PPI use was defined as duration prior to that visit, sorted according to exposure (1 day to 2.8 years, more than 2.8 years to 4.4 years, and more than 4.4 years). Cumulative PPI use ranged from 112 days to 20.3 years by 2011; median use was 3.8 years and mean use was 4.4 years. Dementia status was determined by exam at in-person visits 6 and 7; for those only reached by phone, the Six-Item Screening tool was conducted, with follow-up as appropriate. The researchers identified 585 cases of dementia over median follow-up (10.2%).
Current users of PPIs at Visit 5 (n = 1,450) were not associated with a significantly higher risk of developing dementia during follow-up than those not using PPIs (HR, 1.05). Among cumulative users (n = 1,490), participants who had used PPIs for more than 4.4 years by Visit 5 were at a 38% higher risk of developing dementia later in life (HR, 1.38) compared to those who had never used PPIs. Short-term (1 day to 2.8 years) and intermediate cumulative use (2.8 years to 4.4 years) were not associated with a significant risk of dementia.
The long-term nature of ARIC enabled these researchers to consider the long latency of dementia. Further studies are needed to enable us to understand possible pathways for the development of dementia related to this long-term cumulative use of PPIs. (Northuis, C., et al. (2023). Cumulative use of proton pump inhibitors and risk of dementia: The Atherosclerosis Risk in Communities study. Neurology. Advanced online publication. Retrieved October 2023 from https://n.neurology.org/content/neurology/early/2023/08/09/WNL.0000000000207747.full.pdf
Released: September 2023
Nursing Drug Handbook
© 2023 Wolters Kluwer