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Review Finds JAK Inhibitors More Effective for Moderate to Severe AA Compared With Established Therapies


Baricitinib and other oral JAK inhibitors show promise as effective treatments for moderate-to-severe alopecia areata (AA), with fewer adverse effects compared with traditional options.

Alopecia surrounded by medication | Image Credit: greenapple78 - stock.adobe.com

Alopecia surrounded by medication | Image Credit: greenapple78 - stock.adobe.com

Patients with moderate-to-severe alopecia areata (AA) identified baricitinib and other oral Janus kinase (JAK) inhibitors as effective treatment routes compared with systemic corticosteroids, topical immunotherapy, cyclosporine A, methotrexate, and azathioprine.

Researchers extracted data from systematic literature reviews into a subsequent narrative review to find available evidence pertaining to efficacy and tolerability of treatments currently recommended for adults with moderate-to-severe forms of AA.

Out of the total 53 records retained, 9 reported from 7 randomized controlled trials (RCTs) vs placebo and 44 reported data from unique RCTs with no placebo arm, non-randomized trials, or observational studies.

The narrative review examined the effectiveness of systemic corticosteroids for hair loss. While some patients (40% in 1 study) showed regrowth after 3 months, this benefit usually did not last. There were only 2 patients who achieved more than 60% regrowth. Across studies, relapse rates were high (25%-100%) after stopping the medication.

Systemic corticosteroids also caused adverse effects (AEs) in many patients (55% vs 13% with placebo), including acne, weight gain, and various other issues.

Researchers examined data from 13 mid-sized category 2 studies on topical immunotherapy, often involving a substance called diphenylcyclopropenone (DPCP). These studies did not use the same measures for disease severity or treatment success. In patients who completed the studies, complete hair regrowth varied significantly, ranging from 0% to 52%. However, after stopping treatment, hair loss relapsed in a substantial portion of patients, with rates ranging between 22% and 69%.

Common AEs in topical immunotherapy include swollen lymph nodes, skin irritation on the face or neck, widespread rash, eczema, itching, skin darkening, and hives. These AEs were reported in various studies, with 6 to 25% of patients stopping treatment due to them.

One study reported the efficacy of cyclosporine A, mostly used in monotherapy, as showing no significant improvement in hair loss severity. However, other studies reported up to 55% of patients achieving substantial hair regrowth. Some patients relapsed after stopping treatment.

Most patients (83%) experienced AEs, including infections, muscle problems, gastrointestinal symptoms, and high blood pressure. This finding was consistent across various category 2 studies.

The effectiveness methotrexate has on hair regrowth is missing strong evidence. While some patients showed improvement at 6 months, it was not statistically significant compared to other treatments. Additionally, none of the patients achieved complete scalp regrowth. Stopping treatment led to relapse in most cases. Methotrexate also carries AEs such as gastrointestinal issues, leukopenia, and elevated liver enzyme levels.

The narrative review found no placebo controlled RCT identified in azathioprine treatment. Collected data found 6 patients who achieved greater than or equal to 75% scalp hair regrowth and only 2 relapses after withdrawal of azathioprine. AEs such as diarrhea, elevation of liver enzymes, pancreatitis, and bone marrow suppression occurred in 5 patients with treatment discontinuation among 4 patients.

Studies examined JAK inhibitors, mostly used in monotherapy with tofacitinib, for hair loss. Tofacitinib showed strong efficacy (P < .001). Efficacy of baricitinib was achieved in patients with various degrees of scalp hair loss and benefits patients without initial responses. Baricitinib 4 mg was effective in eyebrow and eyelash regrowth, with lower response rates at 2 mg. Patients benefited from JAK inhibitors regardless of their initial response, but hair loss returned after stopping tofacitinib.

Upper respiratory tract infections, urinary tract infections, nasopharyngitis, acne, blood creatine phosphokinase, and transaminase were among JAK inhibitor AEs, with mostly mild or moderate severity across studies.

Multiple limitations hampered the analysis. Studies varied widely in design, population, and methodology. Inconsistent severity definitions, outcome measures, and hair regrowth assessment methods prevented a combined analysis.

The research identified promising results for baricitinib, a medication approved by the European Medicines Agency and FDA, for severe AA. Other unapproved oral JAK inhibitors showed potential in this area as well.


Egeberg, A., Linsell, L., Johansson, E. et al. Treatments for moderate-to-severe alopecia areata: A systematic narrative review. Dermatol Ther (Heidelb). 2023;13:2951-2991. doi:10.1007/s13555-023-01044-5

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