NEW ORLEANS — In the nearly 1 year since the Janus kinase (JAK) inhibitor baricitinib was approved for adults with severe alopecia areata (AA), mounting long-term efficacy and safety data suggest that the earlier candidates take the drug in the course of their disease, the better.
“The journey to JAK inhibition in alopecia areata has been incredible,” Raj Chovatiya, MD, PhD, assistant professor of dermatology and director of the center for eczema and itch at Northwestern University, Chicago, said at the annual meeting of the American Academy of Dermatology. “JAK inhibitors are here to stay, and I think baricitinib offers an amazing opportunity for the right patients.”
The efficacy and safety of baricitinib (Olumiant) for AA was studied in two randomized, double-blind, placebo-controlled trials (BRAVE-AA1 and BRAVE-AA2) with patients who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool (SALT) for more than 6 months. Patients in these trials received either a placebo, 2 mg of baricitinib, or 4 mg of baricitinib every day. The primary measurement of efficacy for both trials was the proportion of patients who achieved a SALT score of 20 or less, or at least 80% scalp hair coverage at week 36. The researchers found that 36%-39% of individuals in the 4-mg arm achieved a SALT score of less than 20, compared with 19%-23% of individuals in the 2 mg arm. Similar outcomes were observed for eyebrow and eyelash hair loss.
Most adverse events observed in BRAVE-AA1 and BRAVE-AA2 were in the mild to moderate range, and the actual number of adverse events leading to permanent discontinuation was extremely low. The most common adverse events were upper respiratory tract infections, headache, nasopharyngitis, acne, urinary tract infections, and an increase in blood creatine kinase.
Baricitinib is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other potent immunosuppressants, Chovatiya said. Required lab evaluations include baseline testing for tuberculosis and viral hepatitis; CBC, hepatic function, and renal function at baseline and then as clinically indicated; and lipids after 12 weeks of therapy, then as clinically indicated. The recommended starting dose of baricitinib is 2 mg per day, which can be increased to 4 mg per day if the response is not adequate. “However, for patients with nearly complete or complete scalp hair loss, with or without substantial eyelash or eyebrow hair loss, 4 mg once daily is recommended,” he said. “Once an adequate response is achieved, it’s recommended to reduce from 4 to 2 mg daily.”
52-Week, 76-Week Data
According to pooled data from BRAVE-AA1 and BRAVE-AA2 published online March 1, 2023, efficacy continues to increase out to 52 weeks. Specifically, by week 52, 39% of individuals in the 4 mg arm achieved a SALT score of 20 or less, compared with 22.6% of individuals in the 2 mg arm. “You see similar linear growth in the eyebrow and eyelash response loss as well,” Chovatiya said.
In other findings, patients in the 4 mg treatment arm who achieved a SALT score of 20 or less at week 52 were eligible for randomized down titration, provided that they had stayed on the same dose of baricitinib from initial randomization. According to data from baricitinib manufacturer Eli Lilly, 77.5% of patients who stepped down to the 2 mg dose from the 4 mg dose at week 52 achieved a SALT score of 20 or less at week 76, Chovatiya said. “If I can keep someone on 4 mg that’s great, but it looks like you can go to a lower dose and do a pretty good job,” he said.
Patients in the baricitinib arms who achieved a SALT score of 20 or less at week 52 were eligible for randomized withdrawal, provided that they had stayed on the same dose of the drug from initial randomization. According to Chovatiya, 89.4% of individuals who remained on the 4 mg dose to week 76 maintained a SALT score of 20 or less, compared with 33.3% of those who switched from the 4 mg to placebo. “The takeaway here is that clinically, longitudinal treatment looks to be required in this time period” for continued efficacy, he said. “However, what this looks like in the real world remains to be seen.”
A recently published integrated analysis of safety data from BRAVE-AA1 and BRAVE-AA2 reported that no deaths occurred and of the few reported serious infections, nearly half were COVID-19. There was a single case of multidermatomal herpes zoster and no cases of tuberculosis. One patient with risk factors for MI had an MI during a placebo-controlled period, and one study participant with a history of COVID-19 infection developed a pulmonary embolism at day 638. There was one case each of chronic lymphocytic leukemia, B-cell lymphoma, breast cancer, and appendicitis.
Baseline Severity and Treatment Response
“Does treatment response vary with baseline disease status?” Chovatiya asked. “Yes. People with very severe hair loss [defined as a SALT score of 95 or higher] tended to do worse, while the rest of the study population did even better — an almost twofold difference. This means that you want to treat as early as you possibly can. It’s interesting to note that you don’t see this difference as much in the case of eyebrows and eyelashes. This makes sense, though. Eyebrows and eyelashes probably behave differently in terms of growth than the scalp does.”
Certain baseline characteristics of patients in BRAVE-AA1 and BRAVE-AA2 portended better outcomes. Women tended to fare better than men, but individuals who had longer histories of AA did not respond well. “People who had a shorter duration of their current episode of AA also did better than people who had a longer current episode, so we want to think about treating as soon as we possibly can,” Chovatiya said.
Chovatiya disclosed that he is a consultant to, a speaker for, investigator, and/or a member of the advisory board for several pharmaceutical companies, including Eli Lilly.
This story originally appeared on MDedge.com, part of the Medscape Professional Network.
Source: Read Full Article