A 6-month trial of oral JAK inhibitors has been identified as the primary first-line treatment for severe alopecia areata (AA) in the newly published and first-ever consensus statement to guide treatment of this condition.

The consensus statement placed treatment options, including JAK inhibitors, into an evidence-based context for controlling AA in its severest form, according to the senior author, Arash Mostaghimi, MD, MPA, MPH, associate professor of dermatology at Harvard University in Cambridge, Massachusetts, and director of the inpatient dermatology consult service at Brigham and Women’s Hospital in Boston.

“In the past few years, alopecia areata has gone from having no FDA-approved therapies to three JAK inhibitors with, we hope, a fourth one on the way soon,” Mostaghimi told Medscape Medical News.

“Given this level of innovation, it’s important to take a step back and take full stock of our traditional literature and what we’ve learned about our newer therapies to develop guidance for the best care of our patients,” he added.

Thirty AA Experts Provided the Consensus

The Delphi method of consensus involved a series of surveys sent to more than 35 highly experienced dermatologists invited to participate. Of these, nearly 30 participated in all three rounds.

Using the 2022 AA Scale, severe AA was defined as ≥ 50% scalp hair loss. AA can also be considered severe in patients with moderate scalp hair loss (21%-49%) or even mild loss (≤ 20%) on the basis of one or more of four other features: impaired psychological function related to AA; significant involvement of eyebrows or eyelashes; inadequate response to 6 months of treatment; and a multifocal positive hair pull test consistent with progressive AA.

In recommending JAK inhibitors as first-line treatment for severe AA, the consensus statement specifies that the three oral JAK inhibitors now approved for this indication are preferred. Furthermore, the statement contains an emphasis on maintaining the index JAK inhibitor uninterrupted on a consistent dose for 6 months. The three JAK inhibitors approved by the FDA for severe AA are baricitinib (Olumiant), ritlecitinib (Litfulo), and deuruxolitinib (Leqselvi).

If there is an inadequate response at the end of this period, the statement says, options include using a higher dose, switching to a different JAK inhibitor, or adding one or more of the adjunctive therapies on a list that includes oral or topical minoxidil; oral, topical or intralesional steroids; and topical prostaglandins.

As an alternative to first-line JAK inhibitors, the consensus statement recommends consideration of the interleukin-4 receptor inhibitor dupilumab (Dupixent) in patients with active atopic disease or a history of atopy.

Evidence Reviewed for Empiric AA Therapies

A long list of therapies used empirically or with limited data — some for decades — was reviewed and considered in the consensus statement. For some, such as methotrexate, cyclosporine, hydroxychloroquine, and ultraviolet phototherapy, there was a consensus that available data are not sufficient to support a role in severe AA. Consensus was defined as agreement among at least 70% of participants.

For others, such as platelet-rich plasma injections, antihistamines, and anthralin, no consensus was reached on whether available evidence does or does not support benefit.

The consensus statement included a lengthy section on coping resources, acknowledging that mental health support and patient advocacy organizations do appear to offer benefit for those struggling with the psychological burden of severe AA. Camouflage strategies were recommended specifically as one coping option.

Mostaghimi cautioned that the new consensus statement is relevant only to adults with severe disease. In the review, it became clear that evidence-based recommendations could not now be made for subgroups such as children, pregnant patients, patients with less severe disease, or those with comorbidities.

“Although it’s exciting to have guidelines for patients with severe disease, it’s important to acknowledge how limited they are due to the lack of head-to-head data between JAK inhibitors and the limited data for other classes of medication,” he said.

Ultimately, a systematic review of the data is playing an important role in defining knowledge gaps, and it might help guide future studies and trials to address unanswered questions, according to Mostaghimi.

Susan C. Taylor, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and a co-author of the consensus statement, emphasized the point that the consensus group was limited by available data.

“As more scientific data become available on alopecia areata in patients with concomitant comorbidities, or children, or various demographic groups, or those with different hair types, then that data will be reviewed by the guidelines or consensus groups,” she told Medscape Medical News.

Only when differences in diagnosis or response to therapies are based on good-quality data can “guidelines be appropriately updated,” she added.

For clinicians who treat severe AA, the important role assigned to JAK inhibitors in the consensus statement will not be a surprise. However, Luis A. Garza, MD, PhD, professor of dermatology at Johns Hopkins University in Baltimore, believes this type of evidence-based statement has enormous clinical value.

Document May Help Secure Reimbursement

“Insurance companies look for any excuse to deny coverage for expensive therapies, but with a published consensus statement, we now have something to cite when seeking reimbursement,” Garza, who has a research interest in AA and was not an author of the statement, told Medscape Medical News.

This is vital for patients with severe AA. For small patches of hair loss, there are already options — such as intralesional steroid injections — that typically yield good results, but Garza emphasized that these guidelines will help standardize therapy in severe disease.

“This statement could be particularly helpful for getting dupilumab for patients with the potential to benefit,” said Garza, noting this monoclonal antibody must now be prescribed off-label for AA.

He pointed out that an evidence-based document will also be helpful to clinicians uncertain about the evidence surrounding adjunctive therapies.

Asked about the recommendation regarding the extended 6-month first-line course of JAK inhibitors, Garza agreed that very late responses are uncommon but do occur. He thinks a long initial course of JAK inhibitors is appropriate even if the exact timing of adding adjunctive therapies or switching to an alternative drug is “the art of medicine.”

“If I am not seeing any significant hair regrowth by 4 months, I might start to think about the next step,” he said. “But given the fact that we often need prior authorization [from the patient’s insurance] for a switch, the patient might still complete a 6-month course before we get a new treatment started.”

The authors worked in partnership with the National Alopecia Areata Foundation (NAAF) and the American Hair Research Society to develop the consensus statement. “This is an important step forward in improving care, access, and understanding for people living with alopecia areata,” according to a statement from NAAF, which added that the recommendations “help dermatologists and other healthcare providers, patients, and insurers understand recommended treatments and what quality care should look like.”

More information on the recommendations, including guides for patients and healthcare providers, can be found on the NAAF website.

Mostaghimi reported financial relationships with AbbVie, Astria, Boehringer Ingelheim, Dren Bio Labs, Indomo, Legacy Healthcare, Lilly, Matchpoint, Pelage, Q32 Bio, Pfizer, Soterios, and Sun Pharma. Garza reported financial relationships with Eli Lilly, Sun Pharma Advanced Research Company, and Sun Pharma. 

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including oncology, for several decades.