A new era for alopecia areata: New treatments and improved knowledge of the condition

The almost worldwide approval of the oral JAK1/JAK2 inhibitor baricitinib for treatment of alopecia areata (AA) in adults, following the publication of two phase 3 trials,1 has opened a new era for AA. The possibility to achieve a meaningful long-term hair regrowth is now a reality for patients with AA, and other drugs of the JAK inhibitors family, as well as drugs targeting immune reactions, are coming, to enrich our portfolio of therapies. The approval of baricitinib for AA has also arisen the attention towards this condition. Well known features and new evidence regarding AA pathogenesis, course and response to treatment have been recently detailed and divulgated, not only by scientific media, but also by the general press and social media, getting a worldwide resonance. Some of this knowledge derives from the clinical studies for drug approval. The evidence that hair regrowth in AA can be induced by drugs that block inflammatory cytokine signalling and avoid cytotoxic T-cell activation is a clear definitive proof that AA is an autoimmune condition. Dermatologists now know that AA should be treated according to its pathogenesis and cannot anymore be dismissed, as often occurred in the past, as a stress-induced hair loss. The long-lasting request of patients' associations to have health institutions taking care of them as they do for other patients with autoimmune diseases has moved a step forward. The need to design reliable clinical trials with objective endpoints has led to the development of validated scales to grade AA severity: all new trials utilize the SALT score to assess the extent of scalp AA, with a SALT score >50 indicating severe forms and a SALT ≤20 indicator of treatment response.2 SALT score is now used in clinical practice both for treatment decision and periodic monitoring. Further scales have been developed for staging severity of AA of eyebrows and eyelashes, which have a strong physical and psychological impact on patients. A great attention has indeed been devoted to assessing quality of life of patients with AA, which is associated with significant burden, including anxiety and depression and work and activity impairment, especially for patients with severe forms.3 The BRAVE-AA1 and BRAVE-AA2 trials are still ongoing and will follow patients for up to 200 weeks: This allows researchers to assess periodically efficacy and safety of baricitinib and to get information about the long-term course of AA in a large cohort of patients. The evidence coming for these studies is of great value to increase our knowledge about AA and its correct management, as well as our capacity to guide expectation in patients. In addition, several data showed by the trials parallel the evidence we have in real life with the conventional treatments for AA, giving a scientific proof of what was previously only thought and talked. Hair regrowth in AA takes weeks and even months to appear; thus, assessing treatment efficacy should be done after months of administration. Most responses to baricitinib treatment are seen during the first months of treatment, but data at the 52-week follow-up show that response rates continue to increase over time, as some patients have a delayed response.4 This suggests that baseline disease characteristics can influence not only response to treatment, but also speed of response: a short duration of current episode of AA (≤4 years) is associated with higher possibility of hair regrowth, while severity of AA influences speed of response, the more severe forms having a slower response. A long period of treatment appears therefore necessary to induce a meaningful scalp hair regrowth in the very severe forms of AA (alopecia areata totalis and universalis). This is a lesson that we should apply for all treatments for AA. In this issue of The Journal, Senna et al.5 report data on efficacy and safety of baricitinib for severe AA through 104 weeks (more than 2 years) of continuous therapy, either with 2 or 4 mg daily, unrevealing the long-term prognosis of AA patients. It is the longest trial ever conducted on AA. Continuous treatment with baricitinib induced maintenance of SALT score ≤20 in about 90% of patients at Week 104, and induced hair regrowth up to a SALT score ≤20 in about 40% of the patients who did not achieve a SALT score ≤20 at week 52. The proportion of patients achieving eyebrows and eyelash regrowth increased from 52 to 104 week and all questionnaires assessing quality of life showed continuous improvement. These data show that long-term treatment with baricitinib is necessary to maintain results in responders and that results of treatment in partial responders improve in time, as in this group of patients a meaningful hair regrowth can be achieved slowly, over a period di 54–72 weeks. So, while lack of baricitinib effectiveness is consistent with no sign of hair regrowth after 36 weeks of therapy, partial hair regrowth may be an indicator of late response and needs a prolonged treatment and assessment of efficacy at week 72. Incidence of side effects does not seem to increase over time, not influencing safety in prolonged therapies. What are we learning from the long-term experience with baricitinib in AA? That severe AA need prolonged therapy to maintain hair regrowth, and that hair regrowth may take months to appear. This is true for baricitinib, for conventional immunosuppressants, and perhaps for the other JAK inhibitors and the new drugs in study for AA. A new era for AA has arrived, including a new way to deal with chronic and severe forms. None to declare. BMP has served on advisory boards and/or is a consultant for Lilly, Pfizer, Pierre Fabre-Ducray, Difa Cooper, L'Oreal, ISDIN, Legacy Healthcare, Almirall and as speaker for Lilly, Pfizer, Difa Cooper, L'Oreal. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.