Hair Regrowth Observed After Switching Between JAK Inhibitors in Severe Alopecia

New findings suggest that some individuals with severe alopecia areata not responding to 1 or more Janus kinase inhibitors (JAKis) attained significant hair regrowth following a switch to a different JAKi, indicating that treatment failure with 1 agent does not preclude success with another.1

These findings resulted from a retrospective case series evaluating patients’ medical records from July 2014 - September 2023, with the investigators looking at individuals with severe alopecia areata who also failed to respond to 1 or more JAK inhibitors. The data was authored by such investigators as Luiza Kalil, MD, from Yale School of Medicine.

Kalil and coauthors highlighted that there are 3 US Food and Drug Administration (FDA)-approved JAK inhibitors for alopecia areata: ritlecitinib, baricitinib, and deuruxolitinib. The investigators noted the lack of data prior to this analysis on whether someone with alopecia who does not respond to 1 JAKi may respond to an alternate JAKi.2

“This case series retrospectively reviewed records between July 2014 and September 2023 of patients with severe [alopecia areata] who did not respond to treatment with 1 or more JAKis (each JAKi for a minimum of 6 months) before responding (achieved SALT score ≤20) to a different JAKi,” Kalil et al wrote.1

Study Details and Findings

In Khalil and colleagues' case series, a retrospective review of available records between July 2014 - September 2023 was conducted. They evaluated individuals who had not responded to 1 or more JAKis (each JAKi for a minimum of 6 months) prior to attaining a Severity of Alopecia Tool (SALT) score ≤20 to an alternate JAKi.

The investigative team highlighted that those in the cohort exhibited non-response to between 1 and 3 JAK inhibitors prior to gaining clinical improvements with a different JAKi. The team noted the concurrent use of oral minoxidil (2.5–10 mg each day) within 85% of cases, adding that 23% were also treated with intra-lesional triamcinolone.

Although clinical trials have shown comparable efficacy among baricitinib, ritlecitinib, and deuruxolitinib in severe AA, these findings suggest that patients who fail one JAK inhibitor may still respond to another—mirroring similar outcomes reported in atopic dermatitis, where individuals unresponsive to upadacitinib experienced improvement with abrocitinib.

Currently, there are 6 oral JAKis FDA-approved for dermatologic use, yet the investigators noted key gaps remain in understanding these drugs' full therapeutic potential. The conventional classification of JAK inhibitors based solely on selectivity is likely oversimplified; both in vitro and in vivo pharmacologic characteristics, as well as disease heterogeneity, play notable roles. Khalil and coauthors further pointed to the critical nature of dosing parameters in determining therapeutic outcomes.

The investigative team found a lack of definitive conclusions in this case series regarding the overall frequency of JAKi treatment success or failure. In the authors’ clinical practice, tofacitinib was used off-label for about 8 years prior to baricitinib's approval in 2022—followed by ritlecitinib 1 year later. Ruxolitinib, upadacitinib, and tofacitinib remain off-label options for alopecia areata and are not typically considered first- or second-line drugs.

In post hoc analyses from pivotal baricitinib and ritlecitinib trials, findings highlighted by Khalil et al indicate that determining failure of a treatment before 9 months of optimized therapy may be premature. In this analysis, it was noted that switching between JAKis took place after 6–8 months in 7 cases, nearly always prompted by worsening levels of hair loss.

“Although this study is limited by the small sample size, our results show successful treatment of [alopecia areata] with several different JAKis after failure of 1, 2, or even 3 other JAKis, which carries important clinical implications: achieving optimal treatment outcomes will require use of all of the JAKis,” they wrote.1

Clinically, these data underscore that optimal management may require familiarity with multiple JAK inhibitors and individualized selection of drugs. No JAKi has yet demonstrated superior efficacy over alternatives for alopecia areata or atopic dermatitis, and lack of response to 1 does not preclude success with another. Such data reinforce the potential for a personalized medicine approach in which molecular or clinical markers help guide JAKi selection and predict medication responses.

References

1. Kalil L, Craiglow BG, King B. Successful Treatment of Alopecia Areata With One JAK Inhibitor After Failure of Other JAK Inhibitors. JAMA Dermatol. Published online October 08, 2025. doi:10.1001/jamadermatol.2025.3537.

2. Peterson D, Powell M, King B. Less is more? failure of one JAK inhibitor does not predict failure of another one in a patient with alopecia areata. Dermatol Ther. 2021;34(5):e15062. doi:10.1111/dth.15062.