TOPLINE:
When combined with low-dose corticosteroids, a Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib did not result in complete remission (CR) in patients with newly diagnosed or relapsing pemphigus.
METHODOLOGY:
- Long-term use of high-dose corticosteroids for the treatment of moderate to severe pemphigus is associated with adverse events, and targeted treatment, such as rilzabrutinib (a BTK inhibitor), may help minimize exposure to corticosteroids.
- The PEGASUS phase 3 trial, conducted from January 2019 to October 2021 in 19 countries, evaluated the efficacy and safety of rilzabrutinib in patients with newly diagnosed or relapsing moderate to severe pemphigus vulgaris/pemphigus foliaceus (PV/PF).
- Overall, 131 patients aged 18-80 years were randomly assigned to receive 400 mg rilzabrutinib (n = 65) or placebo (n = 66) twice daily for 37 weeks, along with corticosteroids. The corticosteroid dose could be reduced to a minimum of 5 mg/d from week 29 to week 37.
- The primary endpoint was CR, the absence of new and established lesions, from week 29 to week 37 in patients with PV who were on a minimal dose of corticosteroids (≤ 10 mg/d).
- The secondary efficacy endpoints were cumulative corticosteroid dose, cumulative duration of CR with corticosteroid ≤ 10 mg/d, and time to first CR with corticosteroid ≤ 10 mg/d.
TAKEAWAY:
- There was no significant difference in the proportion of patients who achieved CR while receiving the minimal corticosteroid dose during week 29-37 between those on rilzabrutinib and placebo, respectively, among those with PV (24% vs 18%; P = .45), or when those with PF were also included (26% vs 18%, P = .25).
- The mean cumulative corticosteroid dose (5392 vs 4860 mg; P = .05), mean duration of CR (34 vs 54 days; P = .26), and the median time to first CR (not achieved vs 197 days; P = .45) among those on placebo and those with PF/PV, respectively, were not significantly different.
- A prespecified subanalysis showed that a higher percentage of patients had CR when rilzabrutinib was combined with less than the minimal corticosteroid dose at ≤ 5 mg/d (26% vs 12%; P = .04).
- Adverse events were reported in about a quarter of patients in both groups with no new safety signals with rilzabrutinib.
IN PRACTICE:
While the study did not meet its primary efficacy endpoint, “despite early evidence of efficacy” in a phase 2 study, the authors wrote, positive observations using a less-than-minimal corticosteroid dose suggests that BTK inhibition “remains a potential viable therapeutic approach for the treatment of pemphigus.”
SOURCE:
The study, led by Dedee F. Murrell, MA, MD, DSc, Department of Dermatology, St George Hospital, University of New South Wales, Sydney, Australia, was published online in the Journal of Investigative Dermatology.
LIMITATIONS:
Remote visits data were excluded because of unanticipated study management issues related to the COVID-19 pandemic, and the primary efficacy analysis included only patients with PV.
DISCLOSURES:
The study was supported by Principia Biopharma and Sanofi. Five authors declared being current or former employees of the funding agencies, while others declared having ties with several sources, including Principia Biopharma Inc. and Sanofi.
Source link : https://www.medscape.com/viewarticle/rilzabrutinib-plus-low-dose-steroid-fails-pemphigus-trial-2024a100069y?src=rss
Author :
Publish date : 2024-04-03 10:01:15
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