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CSU: Remibrutinib provides rapid clinical benefit

Pooled phase 3 data show that remibrutinib provides rapid and sustained relief in chronic spontaneous urticaria (CSU). Safety data up to week 24 also indicate a favourable profile.

A post-hoc analysis of pooled phase 3 data evaluating remibrutinib as add-on therapy in adults with CSU (≥6 months’ duration) and an inadequate response to second-generation H1-antihistamines was presented by Prof. Ana Giménez-Arnau (Autonomous University and Pompeu Fabra University, Spain) [1]. The analysis focused on daily itch severity scores (ISS) and hives severity scores (HSS) from the REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) trials. To better characterise the timing of symptom onset, average daily ISS and HSS (including a 12-hour assessment at the end of day 1) were evaluated. ISS ranges from 0 (no itch) to 3 (severe itch), and HSS from 0 (no hives) to 3 (>12 hives).

REMIX-1 and REMIX-2 included a total of 613 patients treated with remibrutinib 25 mg twice daily and 312 receiving placebo. The double-blind period lasted 24 weeks. At baseline, the mean ages were 45.0 and 41.7 years across the 2 trials; severe CSU was present in 63.4% and 59.1% of patients; and the mean disease durations were 6.7 and 5.2 years, respectively [2].

Mean daily HSS scores in the remibrutinib and placebo groups decreased from 2.32 and 2.25 at baseline (day -1) to 2.10 in both groups after 12 hours. A clear difference in favour of remibrutinib by day 2 (HSS 1.60 vs 2.06) [1]. This separation continued to day 7 with HSS of 1.11 and 1.87, respectively. Comparable trends were observed for ISS: baseline scores were 2.12 and 2.04; after 12 hours, 1.86 and 1.89;  at day 2, 1.49 versus 1.86; and at day 7, 1.13 versus 1.63, respectively.

An additional perspective was provided by the distribution across severity bands. At baseline, HSS=0 was observed in 1.2% of remibrutinib-treated patients and 0.7% of those receiving placebo; by 12 hours, this increased to 5.8% and 2.4%, respectively. Similarly, ISS=0 was present in <1% of patients in both groups at baseline, increasing to 5.1% with remibrutinib and 2.7% with placebo after 12 hours.

Pooled safety data were comparable between remibrutinib and placebo, with adverse events (AEs) reported in 64.9% and 64.7% of patients, serious AEs in 3.3% and 2.3%, and treatment discontinuation due to AEs in 2.8% and 2.9%, respectively.

The findings are consistent with previously reported long-term data, supporting rapid and sustained improvement in disease activity with remibrutinib, alongside a favourable safety profile.

  1. Mosnaim G, et al. Early symptom improvement with remibrutinib in chronic spontaneous urticaria: Daily Itch Severity Scores and Hives Severity Scores from Phase III REMIX I/II studies. Poster ID 71668. AAD 2026, 27–31 March, Denver, CO, USA.
  2. Metz M, et al. N Engl J Med. 2025;392(10):984-994.

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Novel biologic agent shows promise in severe AA

Rezpegaldesleukin led to reductions in Severity of Alopecia Tool (SALT) scores in the modified intention-to-treat (mITT) cohort. At the higher dose, SALT scores in patients with alopecia areata (AA) decreased by approximately 30% at week 36.

A first-in-class biologic agent targeting regulatory T cells was investigated in the Rezolve AA (NCT06340360), a phase 2b study in patients with severe-to-very severe AA [1]. Rezpegaldesleukin (“rezpeg”), as referred to by the presenter, Prof. David Rosmarin (Indiana University School of Medicine, IN, USA), stimulates regulatory T-cell activity via the interleukin-2 (IL-2) receptor without activating conventional T cells [1,2]. The drug is also under investigation for other dermatologic indications, including atopic dermatitis [1].

The study enrolled 92 adult patients, randomised in a 3:3:2 ratio to receive rezpeg at 24 µg/kg every 2 weeks (Q2W), 18 µg/kg Q2W, or placebo [1]. The primary endpoint was the mean percentage reduction in SALT score at week 36. The study included a 24-week post-treatment follow-up and a 16-week blinded extension for patients with a partial response.

Baseline characteristics included a mean age of approximately 40 years, with 62.9%–78.4% female participants, and mean baseline SALT scores of 80.7 (24 µg/kg) and 76.3 (18 µg/kg). The median time since AA onset ranged from 6.1 to 7.0 years.

In the primary analysis, reductions in SALT score were -28.2% (24 µg/kg), -30.3% (18 µg/kg), and -11.2% (placebo), with neither comparison reaching statistical significance (P=0.186 and P=0.121). However, 4 patients with major protocol deviations (e.g. inadequate washout or unstable disease) were identified and excluded in a post hoc mIIT analysis. In this analysis, results were more favourable: -29.6% (24 µg/kg; P=0.049), and -30.4% (18 µg/kg; P=0.042) versus -5.7% for placebo.

Among secondary endpoints in the mITT population, 29.0% and 21.9% of patients achieved SALT ≤30, and 15.6% and 14.8% achieved SALT ≤20, compared with 8.4% and 6.7% in the placebo arm. Prof. Rosmarin further reported that during the blinded extension phase, additional patients reached these thresholds, with increases of 3 patients for SALT ≤20 and 7 for SALT ≤30. Full extension data up to 1 year are expected soon.

SALT ≤10 responses (mITT) were observed in 11.5% (higher dose) and 8.3% (lower dose) of patients, compared with 0.7% in the placebo group. The mITT analysis demonstrated improvements in eyebrow and eyelash regrowth, with placebo-adjusted rates of 15% and 7%, and 18% and 15%, respectively.

In terms of safety, injection-site reactions, mostly mild-moderate, were the most common treatment-emergent adverse events, occurring in 91.7% of rezpeg-treated patients versus 30% in the placebo group.

According to Prof. Rosmarin, cumulative exposure to rezpeg across 11 studies (approximately 381 patient-years) has not been associated with increased risks of major cardiovascular events, thrombosis, infections, malignancies, acne, or Janus kinase (JAK) inhibitor-associated adverse events requiring laboratory monitoring.

Phase 3 development of Rezpegaldesleukin in AA is planned using a higher dose of 24 µg/kg Q2W.

  1. Rosmarin D, et al. Novel regulatory T-cell enhancing biologic rezpegaldesleukin: phase 2b efficacy and safety results following 36-weeks of therapy in severe-to-very-severe alopecia areata. S023 Late-Breaking Research: Session 1. AAD 2026, 27–31 March, Denver, CO,USA.
  2. Dixit N, et al. J Transl Autoimmun. 2021:4:100103.

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Oral upadacitinib delivers meaningful repigmentation in non-segmental vitiligo

The selective Janus kinase 1 (JAK1) inhibitor upadacitinib produced significantly greater facial and total repigmentation than placebo in adolescents and adults with non-segmental vitiligo across 2 replicate phase 3 trials. Notably, responses continued to deepen through week 48, with no apparent plateau.

Non-segmental vitiligo remains a challenging condition to manage, with treatment largely confined to topical agents and phototherapy. Against this background, the Viti-Up-1 and Viti-Up-2 programme (NCT06118411) evaluated oral upadacitinib as monotherapy in patients with both facial and body involvement, recruited from 18 countries [1]. A previous phase 2 study had already demonstrated the efficacy of this agent in vitiligo [2].

The 2 identically designed trials randomised a combined 614 participants aged ≥12 years (Viti-Up-1, n=308; Viti-Up-2, n=306) in a 2:1 ratio to upadacitinib 15 mg once daily or placebo. Eligibility required a baseline Facial-Vitiligo Area Scoring Index (F-VASI) of ≥0.5 and a Total-Vitiligo Area Scoring Index (T-VASI ) of ≥5. The mean age was around 45 years, and the time since diagnosis ranged from 15.6 to 16.7 years. Around 60% of participants had active disease at baseline, and more than three-quarters had >10% body surface area involvement. Most participants had Fitzpatrick skin types II–IV, and 53–63% had previously received topical therapy. As Prof. Thierry Passeron (Centre Hospitalier Universitaire de Nice, France) noted during the presentation, all the patients were instructed to get photoprotection and did not receive phototherapy or any other concomitant treatments. Following the 48-week double-blind phase, all participants entered a 112-week open-label extension on upadacitinib 15 mg.

Both co-primary endpoints were met. In Viti-Up-1, 19.4% of patients receiving upadacitinib achieved T-VASI 50 at week 48, compared with 5.9% in the placebo group. Additionally, 25% achieved F-VASI 75 (compared with 5.9% in the placebo group). Viti-Up-2 showed similar results, with T-VASI 50 achieved in 21.5% versus 5.9%, and F-VASI 75 in 23.4% versus 6.9%. Response curves showed continued improvement through week 48 without a plateau.

Patient-perceived cosmetic benefit also favoured upadacitinib: on the Vitiligo Noticeability Scale, scores of 4 or 5 (“a lot less noticeable” or “no longer noticeable”) were achieved by 12.6% versus 2.0% in Viti-Up-1, and by 14.6% versus 1.0% in Viti-Up-2. Multiple secondary dermatological endpoints, including F-VASI 50 and F-VASI 90 at week 48, F-VASI 75 at week 24, and both physician- and patient-reported global impressions of “much better” change, were statistically significant (P<0.001 for all). T-VASI 75 at week 48 was not significant.

Safety findings were consistent with the established profile of upadacitinib, with no new signals identified. The most common treatment-emergent adverse events (≥5%) were upper respiratory tract infection, acne, nasopharyngitis, and headache. Four serious infections occurred in the upadacitinib arm of Viti-Up-1 (bronchitis and influenza in 1 patient, complicated appendicitis and parainfluenza in others), none of which led to treatment discontinuation.

In summary, oral upadacitinib 15 mg has the potential to serve as a systemic monotherapy in non-segmental vitiligo, delivering clinically meaningful facial and total repigmentation, with a safety profile consistent with prior experience in other indications.

  1. Passeron T. Efficacy and Safety of Upadacitinib in Adolescents and Adults for Treatment of Non-Segmental Vitiligo: Results of Two Phase 3 Studies (Viti-Up). S023: Late-Breaking Research: Session 1. AAD 2026, 27–31, March, Denver, CO, USA.
  2. Passeron T. EClinicalMedicine 2024:73:102635.

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Could an oral targeted therapy finally change the treatment landscape in dermatomyositis?

A first-in-class oral, selective inhibitor of tyrosine kinase 2 (TYK2)/Janus kinase 1 (JAK1) achieved clinically meaningful improvements in adults with dermatomyositis who had failed prior therapies in the phase 3 VALOR trial (NCT05437263). The agent also successfully improved dermatologic manifestations, supporting its potential as a targeted treatment option in this difficult-to-treat disease.

To date, no targeted therapies are approved for dermatomyositis; current standards, such as conventional disease-modifying anti-rheumatic drugs (DMARDs) and intravenous immunoglobulin, are limited by modest efficacy, burdensome administration, and significant toxicity. Against this backdrop, Prof. Ruth Ann Vleugels (Brigham and Women’s Hospital, MA, USA) presented results from the randomised, double-blind, placebo-controlled phase 3 VALOR trial, with simultaneous publication in the New England Journal of Medicine [1,2]. Brepocitinib targets both TYK2 and JAK1, key mediators of proinflammatory cytokines signalling implicated in the pathogenesis of dermatomyositis.

The trial enrolled adults aged 18–75 years with active muscle and skin involvement, randomising them to brepocitinib 30 mg daily (n=81), 15 mg daily (n=81), or placebo (n=79). The mean age was 50.6 years, and 81.3% had moderate-to-severe disease activity at baseline. Stable background therapy with a single antimalarial, a single DMARD, or both was permitted. Patients receiving systemic glucocorticoids were required to taper to ≤20 mg prednisone-equivalent per day before randomisation, although short rescue courses were allowed during the first 12 weeks.

At week 52, the mean Total Improvement Score, defined as the primary endpoint, was 46.5 with brepocitinib 30 mg, compared with 37.5 with brepocitinib 15 mg and 31.2 for placebo. The difference versus placebo was 15.3 points for the higher dose (P<0.001), whereas the 6.3-point difference for the 15 mg arm did not reach statistical significance. All 9 key secondary endpoints favoured brepocitinib 30 mg over placebo.

Cutaneous outcomes were assessed using the Cutaneous Dermatomyositis Disease Area and Severity Index–Activity (CDASI-A) in participants with moderate-to-severe skin disease at baseline (CDASI-A >14). Cutaneous clinical remission, defined as CDASI-A ≤5 at week 52, was achieved in 44% of patients on the 30 mg dose (n=46) and 32% on the 15 mg dose (n=47), compared with 21% in the placebo group (n=53).

Overall adverse event rates were comparable across arms (90%, 86%, and 91%, respectively). However, serious infections occurred more frequently with brepocitinib 30 mg (10%) than with placebo (1%). According to the investigators, these events resolved with appropriate medical management, and most affected patients completed the treatment. Overall trial completion was 87.1%, although discontinuation was more common in the 30 mg arm (25%) than in the placebo group (11%). Notably, 32% of participants receiving the higher dose did not achieve even moderate improvement.

For dermatologists managing refractory dermatomyositis, brepocitinib may offer an opportunity to intervene earlier with a targeted oral agent, potentially reducing reliance on prolonged systemic corticosteroid use and the toxicities associated with conventional DMARDs. An ongoing 52-week open-label extension will further evaluate the long-term efficacy and safety of brepocitinib in this population.

  1. Vleugels RA, et al. Brepocitinib achieves rapid and sustained control of cutaneous disease activity, itch, and skin-related quality of life in dermatomyositis: Results from the phase III VALOR trial. S034: Late-breaking Research Session 2. AAD 2026, 27–31, March, Denver, CO, USA.
  2. Vleugels RA, et al. New Engl J Med 2026; 394: Published March 28, DOI: 10.1056/NEJMoa2503531.

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