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Alopecia areata: Positive results reported for two investigational JAK inhibitors


 

FROM THE EADV CONGRESS

Treatment with deuruxolitinib and ritlecitinib, two investigational Janus kinase (JAK) inhibitors, resulted in substantial regrowth of scalp hair for patients with alopecia areata (AA) in separate studies reported at the annual congress of the European Academy of Dermatology and Venereology.

In the THRIVE-AA1 study, the primary endpoint of a Severity of Alopecia Tool (SALT) score of 20 or lower –which indicates that hair regrowth has occurred on at least 80% of the scalp – was achieved among patients taking deuruxolitinib, which was a significantly higher proportion than with placebo (P < .0001). Importantly, the JAK inhibitor’s effects were seen in as early as 4 weeks, and there was significant improvement in both eyelash and eyebrow hair regrowth.

In the unrelated ALLEGRO-LT study, effects from treatment with the JAK inhibitor ritlecitinib appeared to be sustained for 2 years; 69.6% of patients treated with ritlecitinib had a SALT score of 20 or lower by 24 months.

These data are “very exciting for alopecia areata because the patients selected are very severe,” observed Mahtab Samimi, MD, PhD, who cochaired the late-breaking session in which the study findings were discussed.

THRIVE-AA1 included only patients with hair loss of 50% or more. The ALLEGRO-LT study included patients with total scalp or total body hair loss (areata totalis/areata universalis) of 25%-50% at enrollment.

Moreover, “very stringent criteria” were used. SALT scores of 10 or less were evaluated in both studies, observed Dr. Samimi, professor of dermatology at the University of Tours (France).

“We can be ambitious now for our patients with alopecia areata; that’s really good news,” Dr. Samimi added.

Deuruxolitinib and the THRIVE trials

Deuruxolitinib is an oral JAK1/JAK2 inhibitor that has been tested in two similarly designed, multinational, randomized, double-blind, placebo-controlled phase 3 trials in patients with AA, THRIVE-AA1 and THRIVE-AA2.

Two doses of deuruxolitinib, 8 mg and 12 mg given twice daily, were evaluated in the trials, which altogether included just over 1,200 patients.

Results of THRIVE-AA1 have been reported by the manufacturer. Brett King, MD, PhD, associate professor of dermatology, Yale University, New Haven, Conn., presented a more comprehensive review at the EADV meeting.

He reported that at 24 weeks, SALT scores of 20 or lower were achieved by 30% of adults with AA who were treated with deuruxolitinib 8 mg and by 42% of those treated with deuruxolitinib 12 mg. This primary endpoint was seen in only 1% of the placebo-treated patients.

The more stringent endpoint of having a SALT score of 10 or less, which indicates that hair regrowth has occurred over 90% of the scalp, was met by 21% of patients who received deuruxolitinib 8 mg twice a day and by 35% of those who received the 12-mg dose twice a day at 24 weeks. This endpoint was not reached by any of the placebo-treated patients.

“This is truly transformative therapy,” Dr. King said when presenting the findings. “We know that the chances of spontaneous remission when you have severe disease is next to zero,” he added.

There were reasonably high rates of patient satisfaction with the treatment, according to Dr. King. He said that 42% of those who took 8 mg twice a day and 53% of those who took 12 mg twice a day said they were “very satisfied” or “satisfied” with the degree of scalp hair regrowth achieved, compared with 5% for placebo.

Safety was as expected, and there were no signs of any blood clots, said Dr. King. Common treatment-emergent adverse events (TEAEs) that affected 5% or more of patients included acne and headache. Serious TEAEs were reported by 1.1% and 0.5% of those taking the 8-mg and 12-mg twice-daily doses, respectively, compared with 2.9% of those who received placebo.

Overall, the results look promising for deuruxolitinib, he added. He noted that almost all patients included in the trial have opted to continue in the open-label long-term safety study.

Prescribing information of the JAK inhibitors approved by the U.S. Food and Drug Administration includes a boxed warning about risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. The warning is based on experience with another JAK inhibitor for patients with rheumatoid arthritis.

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