VIENNA – People with the least scalp hair loss at baseline had the greatest and fastest response to the Janus kinase (JAK) inhibitor ritlecitinib (Litfulo) in a new analysis of the phase 3 ALLEGRO-LT study.

A Severity of Alopecia Tool (SALT) score ≤20 was achieved at 6 months by 76.3% of patients who initially had only a quarter to less than half of their scalp affected. A similar score was achieved by 61.2% of those who had a starting hair loss of 50% to <95% and 22.5% of those with almost no hair (95%-100% hair loss). 

At 12 months, 86.4%, 72.9%, and 34% of patients in each of the groups, respectively, achieved this clinically meaningful hair regrowth target. After this, the results plateaued toward the 5-year follow-up, where 85.6%, 79.1%, and 37.5% had met the target. 

These were last observation carried forward (LOCF) data from a post hoc analysis of people with at least 25% hair loss at baseline in the ALLEGRO-LT who had been treated with ritlecitinib.

Brett King, MD, PhD, of Dermatology Physicians of Connecticut, Fairfield, United States, reported the findings here at the European Academy of Dermatology and Venereology (EADV) 2026 Congress.

King said that traditionally, clinicians are accustomed to thinking of using JAK inhibitors in people with alopecia areata when there is at least 50%-100% hair loss. This is based, he explained, on the clinical trial data, although there are real-world data suggesting ritlecitinib has efficacy across the spectrum of disease activity and in those with less severe hair loss.

New Starters Included in ALLEGRO-LT 

ALLEGRO-LT was an open-label, multicenter trial that included patients from the ALLEGRO phase 2b and 3 studies, as well as newly enrolled patients with ≥25% scalp hair loss who had not previously received ritlecitinib and whose current hair loss episode had lasted for no more than 10 years. 

The analysis presented by King only considered these new starters of ritlecitinib. He noted that the approved dose of ritlecitinib was 50 mg once daily and that the new starters also received a 200-mg once daily loading dose for 4 weeks. 

Participants were stratified by their baseline SALT scores: 118 people had a SALT score of 25 to <50, 129 had a SALT score of 50 to <95, and 200 had a SALT score of 95 to 100.

At 5 years, most patients had left the study, with only 13 (11.0%), 20 (15.5%), and 34 (17.0%) completing the study in the three respective severity groups. However, King noted that many patients were removed from the study per the protocol when ritlecitinib became commercially available in 2023 following its approval. This accounted for the departure of 39%, 42%, and 29% of patients in the respective severity groups.

Other reasons for discontinuing study treatment included adverse events (5.1%, 6.2%, and 6.0%), lack of efficacy (3.4%, 2.3%, and 9.0%), and withdrawal of consent (18.6%, 15.5%, and 21.0%) in the respective severity groups.

Across-the-Board Efficacy and Safety

The results showed that good responses to treatment “were achieved across the spectrum of severity,” said King. 

In addition to the achievement of a SALT score ≤20 during the 5-year follow-up, the researchers also recorded the achievement of a higher-bar SALT score of ≤10. At 5 years, 73.7%, 70.5%, and 33.0% of patients with the least, middle, and worst hair loss at baseline achieved this endpoint with higher and quicker responses seen at 6 months and a plateau after 12 months. 

Regarding the safety of ritlecitinib in the de novo cohort at 5 years, King reported there was “nothing new relative to the bigger cohort of patients.” Any adverse event occurred in 89.7% (n = 401), with serious adverse events reported in 6.9% of patients and severe adverse events in 7.6%. 

One death occurred “due to breast cancer deemed unrelated by the investigator,” said King. Then there were “the usual list of suspects that we see in clinical trials,” such as headache (21.7%), nasopharyngitis (14.1%), upper respiratory infection (13.4%), fever (13.2%), acne (12.8%), fatigue (10.5%), and cough (10.3%). Positive SARS-CoV-2 tests and COVID-19 were reported in 24.2% and 12.5% of patients, respectively; the study spanned the pandemic.

King added that adverse events of special interest “often dominate conversations about JAK inhibitors.” Serious infections occurred in 1.3% of patients, malignancies in 0.7%, and major adverse cardiovascular events in 0.9%. There were no cases of venous thromboembolism, and herpes zoster infection occurred in 1.8% of patients, but none were serious or disseminated. 

Risks and Mitigation

Electra Nicolaidou, MD, PhD, professor of dermatology and venereology at the National and Kapodistrian University of Athens, Greece, commented during the session: “Very impressive. JAK inhibitors have changed completely the treatment of alopecia areata; and not only alopecia areata, but also atopic dermatitis and vitiligo, etc.” 

Nicolaidou asked King, “Do you think that herpes zoster is a problem to this group of patients? Your results were okay, but your personal opinion on that?”

King responded, “When I'm speaking to patients about starting a JAK inhibitor or about the adverse event profile, I say there's really only one risk that is quantifiable with this medicine — and it doesn't matter which [JAK inhibitor] we're talking about — and that is the risk of herpes zoster.” He qualified, however, that the risk “might be very tiny to begin with” and that the conversation about the risk of herpes zoster would be very different with a 60-year-old than with a 20-year-old. King observed that all adults starting an immunomodulatory treatment should be vaccinated against the virus in line with current US guidelines.

Long-Term Patient Perceptions 

Jan-Christoph Simon, MD, PhD, professor and chairman of the Department of Dermatology, Venereology, and Allergology at University Hospital Leipzig, Germany, 

asked King, “JAK inhibition in [alopecia areata] has been around for some time. What is your experience [of] following these patients? How do they perceive a lifelong treatment?”

King answered: “I think that people don't struggle too much with staying on them. I have patients now who have been on them for as long as 12 years. And, you know, we try to lower the dose; we're often successful. Some people come off [the drug], actually.”

That said, “some people don't ever want to try [to come off the drug] because they don't want to go back to what is, for many people, the darkest part of their life when they had no hair.” 

Pfizer sponsored the ALLEGRO-LT study. King reported acting as a clinical trial investigator and serving as an advisor, consultant, or speaker for Pfizer, among other pharma companies. His co-authors on the abstract also had ties to Pfizer, with five being employees of the company. 

Nicolaidou and Simon were not involved in the study. They co-chaired the late-breaking news session that the ALLEGRO-LT study findings were presented in. 

Sara Freeman, BSc, MSc, is a freelance medical journalist based in London, UK. She has been reporting for specialist healthcare news organizations for more than 20 years.