Brepocitinib in Dermatomyositis Save
The NEJM reports that brepocitinib, an oral TYK2–JAK1 inhibitor, was studied in a phase 3 trial of refractory dermatomyositis (DM) patients and shown to have significant benefits at the higher dose.
In this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were randomized to either placebo, brepocitinib 30 mg qd or brepocitinib 15 mg qd, while other standard therapies were continued, and glucocorticoids were tapered for 52 weeks. The primary end point was the Total Improvement Score (TIS), a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52.
To be enrolled patients had to have:
- Active muscle disease (MMT-8: 80 to 142)
- Active skin disease by CDASI-A)
- Inadequate response to standard treatment (glucocorticoids, csDMARDs, or IVIG)
A total of 241 patients were enrolled; and the primary endpoint at week 52 (higher is better):
- brepocitinib 30 mg = 46.5 (difference with brepocitinib 30 mg vs. placebo, 15.3; [CI], 6.7 to 24.0; P<0.001)
- brepocitinib 15 mg = 37.5 (difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9; NS)
- placebo = 31.2
Brepocitinib 30 mg was superior across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4.
Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.
This trial demonstrates the efficacy of TYK2/JAK1 inhibition in difficult to treat DM patients (ClinicalTrials.gov number, NCT05437263.)
Continue Reading
Join The Discussion
I presented a case at Southern California Rheumatism society where we had challenges in managing skin condition and our patient responded well to JAK inhibitor for skin findings. I discussed this drug with a physician working on Brepocitinib trial who said its really a nice mechanism.
Finally, a difference in Placebo rates was noted in these graphs compared to previous JAK data.
From industy presentation tables to seeing them in NEJM format. Cant wait to do Journal club on this
THis is exciting to have a new effective Rx option for DM pts. Also encouraging is the early data on alpha IFN ihhibition w/ anifrolumab in DM. Definitely present this and get the feedback of your peers!
Disclosures
The author has no conflicts of interest to disclose related to this subject
If you are a health practitioner, you may Login/Register to comment.
Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.