⚡One-year of remibrutinib in CSU

Good morning — it’s Saturday, October 25, and we’re covering one-year results for remibrutinib in chronic spontaneous urticaria, icotrokinra vs deucravacitinib for psoriasis, and more — plus a new Clinical Snapshot feature in Derm Picks.

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Remibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, delivered durable disease control in antihistamine-refractory chronic spontaneous urticaria (CSU), according to new long-term Phase 3 results published in JACI.

The findings come from the pivotal REMIX-1 and -2 trials, which represent the longest BTK inhibitor data reported in CSU to date.

Investigators randomized 925 adults with antihistamine-refractory disease to remibrutinib 25 mg twice daily or placebo for 24 weeks, followed by open-label treatment through Week 52.

At baseline, 61% had severe disease; ~30% had prior exposure to anti-IgE biologics.

Efficacy remained strong at one year, mirroring responses seen at Week 24. Nearly two-thirds (62–64%) achieved well-controlled disease (UAS7 ≤ 6), while 42–46% were completely free of itch and hives (UAS7 = 0). Improvements were evident as early as Week 1.

Safety at one year was consistent with the placebo-controlled period. No serious adverse events were considered related to treatment. Petechiae were infrequent (4%), limited to the first three months, and not associated with platelet or coagulation abnormalities.

Remibrutinib was FDA-approved last month as the first BTK inhibitor for antihistamine-refractory CSU. It is the only oral alternative to the injectable biologics omalizumab (Xolair) and dupilumab (Dupixent). A recent network meta-analysis of over 11,000 patients ranked remibrutinib and omalizumab as the most effective treatments for antihistamine-refractory CSU.

> Icotrokinra outperforms deucravacitinib in two Phase 3 psoriasis trials: The Lancet published results from the Phase 3 ICONIC-ADVANCE 1 and 2 trials. The studies showed that icotrokinra, a once-daily oral IL-23 receptor peptide, outperformed both placebo and deucravacitinib in moderate-to-severe psoriasis. Investigators enrolled more than 1,500 adults in the randomized trials over a 16–24-week period. By Week 16, 68–70% of patients on icotrokinra achieved clear or almost clear skin (IGA 0/1) versus 9–11% on placebo (P < 0.0001). At Week 24, icotrokinra demonstrated superior efficacy over deucravacitinib, with 68–74% vs 52–55% achieving IGA 0/1 (P < 0.001). Notably, adverse event rates were lower than those with placebo (48% vs 57%) and deucravacitinib (57% vs 65%) at both timepoints. Oral herpes and acne were rare with icotrokinra (<1%) but more common with deucravacitinib (3%). The accompanying editorial described icotrokinra as “a major advance.” It highlighted that a peptide drug can target a cytokine receptor and achieve biologic-level efficacy through oral administration. Patients often prefer oral therapy for convenience. Still, daily dosing requires consistent adherence, while less frequent biologic injections can offer greater freedom from both disease and treatment. FDA and EMA filings for icotrokinra are now underway.

> Delgocitinib reduces Th1/IFN-γ inflammation in frontal fibrosing alopecia trial: A Phase 2a randomized trial published in JID showed that delgocitinib cream, a topical pan-JAK inhibitor, improved both molecular and clinical markers in frontal fibrosing alopecia (FFA). Thirty women applied delgocitinib or vehicle twice daily for 12 weeks, followed by a 12-week open-label extension. At Week 12, expression of selected Th1/IFN-γ–related genes decreased with delgocitinib but not with vehicle. These included CXCL9 (–3.1; P < 0.05), CXCL10 (–2.6; P < 0.10), and IFN-γ (–1.5; P = 0.22). Treated lesions improved by 4% toward a non-lesional transcriptomic profile, whereas vehicle lesions worsened by 33%. The mean disease severity score (FFASS; range 0–25) improved more with delgocitinib than with vehicle (–2.2 vs –0.8; P = 0.02). It continued to improve through the open-label extension. Both hair counts and follicular units per cm² increased at Week 12 with delgocitinib; however, they began to decline again during the open-label extension. Limitations included the small sample size and exploratory nature of efficacy endpoints. Investigators noted that inflammation in FFA occurs in the upper portion of the hair follicle and within the thin skin of the frontal hairline, supporting the biologic rationale for topical JAK inhibition.

> Selective JAK1 inhibitor shows durable regrowth in severe alopecia areata: A Phase 3 trial published in JAAD found that ivarmacitinib significantly improved hair regrowth in adults with severe alopecia areata. As a selective oral JAK1 inhibitor, the drug may offer a differentiated option within the JAK inhibitor class. Investigators randomized 330 patients to ivarmacitinib 4 mg, 8 mg, or placebo once daily for 24 weeks. Baseline scalp coverage was low, averaging 21% (SALT 79; range 0–100). By Week 24, 35% and 41% of patients on ivarmacitinib 4 mg and 8 mg achieved ≥80% scalp coverage (SALT ≤20), compared with just 1% on placebo (P < 0.001). After 24 weeks, investigators re-randomized patients on placebo to ivarmacitinib 4 mg or 8 mg, and all continued treatment for another 28 weeks. Responses deepened by Week 52, with 47% and 63% of patients initially on 4 mg and 8 mg reaching SALT ≤20. Treatment was generally well tolerated; moderate and serious adverse events were uncommon. Three patients discontinued during the placebo-controlled period: two on 4 mg (follicular lymphoma, myocardial infarction) and one on 8 mg (thyroid cancer). The authors noted efficacy and safety were comparable to approved JAK inhibitors. However, they cautioned against cross-trial comparisons.

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