Episode 48 - Deucravacitinib in patients with alopecia areata in a phase II trial

In this episode of BJD Talks, Sam and Meera discuss the article ‘Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in patients with alopecia areata: efficacy and safety results of a phase II, multicentre, randomized, double-blinded, placebo-controlled trial’ by Kinget al. The full article can be accessed at https://doi.org/10.1093/bjd/ljag109

 *This podcast was generated by an AI tool created by 67Bricks for the British Association of Dermatologists*

Transcript

SPEAKER_00 0:00

Welcome to BJD Talks, the official podcast of the BJD. I'm Sam.

SPEAKER_01 0:04

And I'm Mira. In this episode, we will be discussing the article by Brett King et al. Dukravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor in patients with alopecia ariata, efficacy and safety results of a phase 2 multicentre randomised double-blinded placebo controlled trial from March 2026 and included in the August 2026 issue.

SPEAKER_00 0:32

To start, alopecia areata, or AA, is an immune-mediated inflammatory disease causing non-scurring hair loss. It's chronic, unpredictable, and often profoundly distressing to patients.

SPEAKER_01 0:43

Jack inhibitors have become first-line therapy for patients with severe alopecia ariata, but fewer than half of patients achieve complete or near-complete scalp hair regrowth.

SPEAKER_00 0:53

This trial explored ducrovacitinib, a selective TIC2 inhibitor. It specifically targets the regulatory rather than catalytic domain of TIC2. Having shown promise in plaque psoriasis, the question was whether it could be effective for AA.

SPEAKER_01 1:09

The phase 2 trial was conducted across six countries. 94 patients with severe AA, indicated by a SALT score of at least 50, were randomized into placebo, 6 mg once daily, or 6 mg twice daily groups.

SPEAKER_00 1:25

The primary endpoint was the reduction in SALT score at 24 weeks. Secondary goals included achieving a salt score of 20 or lower or reaching an investigator global assessment score of nearly clear or clear. What did the data reveal, Mira?

SPEAKER_01 1:39

Disappointingly, the trial didn't meet its primary endpoint. Changes in SALT scores between Ducrovacitinib and placebo were minimal. For the twice-daily group, the difference in salt score reduction was 8.2 compared to placebo, but with a p-value of 0.045, its clinical significance is doubtful.

SPEAKER_00 2:00

No secondary endpoints improved either. Interestingly, six participants achieved a SALT score of 20 or less over 52 weeks, most during the extended treatment period.

SPEAKER_01 2:12

This hints that longer treatment might benefit some. However, the trial was terminated early for business reasons, so broader outcomes beyond 24 weeks remain unclear.

SPEAKER_00 2:22

Looking at safety, ducrovacitinib was well tolerated. Common side effects included nasopharyngitis, acne, and mild folliculitis. No major cardiovascular events or severe abnormalities in laboratory results occurred.

SPEAKER_01 2:36

Yes, the safety profile was consistent with expectations, but its limited efficacy may be due to the role of TIC2. Ducrovacitinib inhibits cytokines like IL12 and IL23, which might not be central to AA pathogenesis. Broader JAC inhibitors targeting IL-15 and IFN gamma pathways seem more promising.

SPEAKER_00 2:58

It's a reminder that mechanism of disease and mechanism of action of a drug matter. The results suggest that TIC2's narrower scope of cytokine inhibition may not be effective for AA.

SPEAKER_01 3:09

While this trial didn't meet expectations, it is exciting to see other therapeutic targets being trialled for AA.

SPEAKER_00 3:15

In summary, Ducrovacitinib didn't significantly promote regrowth in severe AA within a 24 week period.