Brepocitinib Associated with Improved Skin Outcomes in Dermatomyositis
Key Takeaways
- In adults with dermatomyositis in the phase 3 VALOR trial, brepocitinib 30 mg was associated with better skin-specific outcomes than placebo.
- Improvement in cutaneous disease activity was seen by week 4 and was reported through week 52 with brepocitinib 30 mg. Exploratory findings for itch remission and skin-related quality-of-life improvement also favored brepocitinib 30 mg from week 4 onward.
- The authors described brepocitinib safety as consistent with approved Janus kinase and tyrosine kinase 2 inhibitors.
The multinational trial enrolled 241 participants across 90 sites in 20 countries and assigned once-daily brepocitinib 30 mg, brepocitinib 15 mg, or placebo. Skin-focused outcomes included key secondary measures of change in Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) and clinically meaningful CDASI-A response, while exploratory outcomes included itch on the Peak Pruritus Numeric Rating Scale (PP-NRS), skin-related quality of life on Skindex-16, Cutaneous Dermatomyositis Activity-Investigator’s Global Assessment (CDA-IGA) clear or almost clear status, and functional skin remission. Clinically meaningful CDASI-A response was defined as at least 40% relative and at least a 4-point absolute improvement, and functional skin remission as CDASI-A 5 or lower.
By week 4, mean change from baseline in CDASI-A favored brepocitinib 30 mg over placebo at -6.4 versus -3.5, for a between-group difference of -3.0 (95% CI, -4.6 to -1.4; P<.001). Early clinically meaningful CDASI-A response also occurred more often with brepocitinib 30 mg than with placebo.
Exploratory patient-reported findings moved in the same direction, with week 4 itch remission on the PP-NRS reported in 38.3% of participants receiving brepocitinib 30 mg versus 19% with placebo. Benefits on the key secondary CDASI-A measures, along with exploratory itch and skin-related quality-of-life measures, were reported at all assessed time points through week 52. Among participants with moderate to severe baseline skin disease, the exploratory CDA-IGA clear or almost clear outcome at week 52 was achieved in 45.7% with brepocitinib 30 mg versus 21.8% with placebo.
Brepocitinib had a profile consistent with approved Janus kinase (JAK) and tyrosine kinase 2 (TYK2) inhibitors.
According to the authors, once-daily brepocitinib 30 mg produced rapid, durable, and remission-level control of skin disease in dermatomyositis in this secondary analysis, with an acceptable safety profile.
Clinician Questions
Which patients with dermatomyositis were represented in the VALOR skin analysis of brepocitinib?
The VALOR skin analysis included adults with dermatomyositis and active skin and muscle disease who were enrolled in a 52-week phase 3 randomized trial conducted at 90 sites in 20 countries. The remission-level week 52 findings were reported specifically for the subgroup with moderate to severe baseline skin disease.
How was clinically meaningful skin response defined for brepocitinib in dermatomyositis?
Clinically meaningful skin response was defined as a Cutaneous Dermatomyositis Disease Area and Severity Index-Activity improvement of at least 40% relative to baseline and at least 4 points in absolute terms. Functional skin remission was defined separately as a CDASI-A score of 5 or lower.
What does the safety statement for brepocitinib in this dermatomyositis analysis actually establish?
The authors reported that brepocitinib had a safety profile consistent with approved JAK and TYK2 inhibitors and concluded that skin control occurred with an acceptable safety profile in this secondary analysis.