Alopecia areata and ritlecitinib: Unravelling response trajectories

Abstract

Alopecia areata (AA) is a complex autoimmune condition characterised by non-scarring hair loss, which can progress to more extensive forms such as alopecia totalis (AT) or alopecia universalis (AU). In this issue of the JEADV, King et al. investigate the long-term response patterns to ritlecitinib, a Janus kinase (JAK3)/TEC family kinase inhibitor.¹ This study presents a post-hoc analysis of pooled data from the ALLEGRO-2b/3 and ALLEGRO-LT trials, evaluating response trajectories over 24 months in patients receiving ritlecitinib 50 mg daily.

A key strength of this study is its categorisation of patients into responders, non-responders, relapsers, and partial responders based on the Severity of Alopecia Tool (SALT) score. The identification of six distinct responder groups—early, middle, and late responders, as well as non-responders, partial responders, and relapsers—adds a novel contribution to the literature on AA treatment. The study found that 45.5% of patients achieved a SALT score ≤ 20, with 46.0% of responders attaining complete hair regrowth (SALT score of 0). Furthermore, 93.1% of these responders maintained their response through 24 months, underscoring the durability of ritlecitinib's therapeutic effects. Notably, 10.5% of patients responded only after more than a year of treatment, highlighting the need for prolonged therapy before evaluating efficacy.

Previous studies have examined response trajectories in AA patients treated with baricitinib (4 mg or 2 mg daily).² A post-hoc analysis using growth mixture modelling of two phase III trials categorised responders into early, gradual, and late groups based on the time required to achieve SALT30. However, that analysis was limited to a 52-week follow-up period. Both studies demonstrated that patients with a shorter disease duration and lower baseline SALT scores were more likely to achieve a clinical response. The ritlecitinib analysis further revealed that female patients were more likely to experience a favourable clinical response, a novel demographic finding in AA treatment research.

The study confirms that greater disease severity (higher SALT scores, presence of AU/AT) correlates with poorer treatment response, consistent with baricitinib studies. These findings suggest that initiating systemic JAK inhibitors before the onset of severe AA (e.g. AT/AU) may yield better outcomes for patients.

Despite these insights, future research is needed to optimise the management of severe AA cases. First, analysing response patterns in other affected areas, such as the eyebrows and eyelashes, could provide valuable predictive markers for scalp response. Additionally, reports suggest that combination therapies may accelerate hair regrowth. A small case report indicated that combining systemic steroids with baricitinib led to faster hair regrowth in severe AA patients.³ Another important question is whether switching to an alternative JAK inhibitor could benefit patients who fail to respond to either baricitinib or ritlecitinib, as it was suggested by clinical case reports.⁴ A dedicated clinical trial comparing these treatment strategies would help clarify their relative benefits and optimal patient selection criteria.

In conclusion, this study provides valuable insights into the long-term response patterns of patients with AA treated with ritlecitinib, emphasising the importance of sustained therapy. The findings reinforce that less severe and shorter-duration AA cases respond better, aligning with previous baricitinib research. Further randomised controlled trials are necessary to directly compare JAK inhibitors and explore potential combination therapies that could enhance treatment outcomes. While this study represents an important step in refining AA treatment strategies, its findings require further validation through larger, controlled trials to solidify its clinical implications.

JS received consulting fees and payment or honoraria for lectures, presentations, and speakers from Abbvie, Pfizer, Almirall, Eli Lilly and Company, and Sanofi.

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