2024-03-26 08:44:24
San Diego, USA – In separate studies evaluating treatments for severe forms of alopecia, Janus kinase (JAK) inhibitors produced clinically significant hair regrowth, according to recent data presented at the 2024 Annual Meeting of the American Academy of Dermatology (AAD).
In a study of brepocitinib, the target was scarring alopecia (CA), a form of hair loss for which there is no approved treatment. In the other, a subanalysis of phase 3 trials of ritlecitinib for alopecia areata (AA), hair regrowth was demonstrated in the subset of patients who started the study with alopecia totalis or alopecia universalis (AT/AU).
Reflecting comments from several experts, including one of the moderators of the closing session, April W. Armstrong, professor and chief of dermatology at the University of California, Los Angeles, said the study on AC, which linked clinical response to changes in AC biomarkers, suggested the findings were a potential breakthrough.
“This is the first placebo-controlled study with an oral JAK inhibitor that not only shows that scarring alopecia may be reversible, but also provides insight into the mechanism of action and which patients might experience it. answer best,” Emma Guttman-Yassky said in an interview. Emma Guttman-Yassky, professor of dermatology and immunology and director of the Inflammatory Skin Disease Laboratory at the Icahn School of Medicine at Mount Sinai (New York, United States) was the principal investigator of the study.
Cicatricial alopecia and brepocitinib
For the scarring alopecia study, 49 AC patients were randomized in a 3:1 ratio between brepocitinib, a first-in-class inhibitor that targets both JAK1 and TYK2, and placebo. Due to the small study size, the primary endpoint was change in AC biomarkers. The secondary outcome was clinical response, but due to a correlation between the two, they were mutually reinforcing.
Among the subtypes, 9 patients included in the study had frontal fibrosing alopecia (FFA), 16 had lichen planopilaris-like alopecia (LPP), and 24 had central centrifugal scarring alopecia (CCCA). All forms of CA are more common in women in general and women of color in particular, including CCCA. For this analysis, FFA and LPP subtypes were considered similar for response assessment and were combined.
Data included a comparison of response and safety during the 24-week randomization phase, as well as additional follow-up after 24 weeks of open-label treatment. During the second phase, all patients receiving placebo were switched to active treatment.
Overall, there was a reduction in all four key scalp inflammatory biomarkers measured in patients in the combined FFA/LLP group. In the placebo group, each of these markers – interferon gamma (IFN-gamma), CCLS, CXCL10 and STAT1 – increased over the same period. In almost all cases, the differences were statistically significant.
In the CCCA subgroup, the same trend (an increase in patients on placebo but a decrease in those on brepocitinib) was observed for CCLS and CXCL10. For IFN-gamma and STAT1, an increase was observed in both placebo and active treatment patients, although the increase was greater for placebo.
In terms of clinical response, brepocitinib improved disease activity indices, particularly in the FFA/LLP group, according to Marguerite Meariman, dermatology resident at Mount Sinai, who presented the results. She called the improvement in clinical activity scores at 48 weeks “dramatic.” Additionally, improvement was apparent within 4 weeks of starting treatment.
For CCCA, a more difficult condition to treat, Dr. Meariman said that lack of progression may be an acceptable response for many patients, but there are also cases of hair regrowth in this subgroup. . Although the improvement was generally not on the order of that seen in patients with FFA/LLP, it suggested that the treatment offered hope even in these more difficult patients.
More studies are planned, but Dr. Meariman said it may be important to focus on early treatment, regardless of AC subtype. She noted that patients whose illness has lasted less than 5 years generally fare better than those whose illness has lasted longer.
Ritlecitinib for AT/AU
The analysis of patients with AT/AU was based on a subset analysis of theALLEGRO phase 2b/3 study on ritlecitinib, which targets JAK3 and TEC kinases. The full results of the ALLEGRO study were published last year in The Lancet .
In the new late breakup analysis, SALT scores (Severity of Alopecia Tool) were assessed based on the observation or last observation reported. In general, responses in the subgroup of patients with AT/AU, who had a median SALT score of 80.3 (meaning 80.3% hair loss) at study entry, did not were only slightly lower than those of the entire trial.
At 24 months, about 50% of patients achieved a SALT score of 20, according to Melissa Piliang, chair of the department of dermatology at the Cleveland Clinic (Cleveland, USA), who presented the data.
In this group, as in the non-AT/AU population, responses increased over time and were maintained as long as patients remained on treatment.
At the more stringent threshold of SALT < 10, the proportion of responders was only slightly lower, meaning that a substantial proportion of patients with AT/AU "achieve 90% or more hair regrowth, which constitutes really a great response,” said Dr. Piliang.
In the subgroup with UA, regrowth of eyebrows and eyelashes was also observed in a substantial proportion, according to Piliang.
Attributed to the often devastating psychological burden of hair loss, patient-reported ratings of these overall responses were generally “even better” than those reported by researchers.
However, Dr. Piliang advised clinicians to treat AA as early as possible. Despite the benefits seen in the AT/AU subgroup, she noted that starting treatment before complete hair loss is associated with a greater likelihood of complete or near complete hair regrowth.
There is no data from the ALLEGRO trial to determine how long hair will regrow after stopping ritlecitinib, which has been approved for the treatment of AA, but Dr. Piliang said patients should be informed that Lifelong treatment is expected in the vast majority of them, whether or not AA has progressed to AT/AU.
“In my experience with JAK inhibitors, you lose the response when you stop taking these drugs,” she said.
Drs. Meariman and Piliang spoke at the closing session of the 2024 American Academy of Dermatology (AAD) Annual Meeting, held March 9 in San Diego, California.
Precautions for use of anti-JAK
The short-term side effects of anti-JAK drugs generally appear to be moderate. However, when the prescription of an anti-JAK is considered, it is appropriate to take into account the need to monitor various biological parameters (hematological and lipids), the contraindication of anti-JAK in the event of pregnancy, as well as as uncertainties persist in terms of tolerance, in particular those relating to the risks of major cardiovascular and thromboembolic events and the carcinogenic risk.
Anti-JAK drugs should only be used in the absence of an appropriate therapeutic alternative in patients identified as being at increased risk of adverse effects:
‒ patients aged 65 and over;
‒ patients with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (long-term smokers or former smokers);
‒ patients with risk factors for malignant tumors.
Funding and links of interest
Dr. Meariman reported a financial relationship with AbbVie. Dr. Piliang reported financial relationships with Eli Lilly, Pfizer and Proctor & Gamble. Armstrong has reported financial relationships with more than 30 pharmaceutical companies, including those that make JAK inhibitors. Dr. Guttman-Yassky has reported financial relationships with more than 30 companies, including those manufacturing JAK inhibitors.
This article was translated from Medscape.com using multiple editorial tools, including AI, in the process. The content was reviewed by the editorial staff before publication. Adapted by Aude Lecrubier.
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