Integrated analysis supports long-term efficacy of ritlecitinib for alopecia areata

An integrated analysis of the pivotal phase IIb/III ALLEGRO and phase III ALLEGRO-LT studies demonstrated the long-term efficacy of the oral JAK3/TEC family kinase inhibitor ritlecitinib for alopecia areata (AA).

Two groups were pooled from ALLEGRO and ALLEGRO-LT. The loading-dose (LD) group comprised participants who received an initial 200-mg dose of ritlecitinib for 4 weeks, followed by 50 mg QD (n=502; mean age 32.9 years, 66 percent female). The other group were on the 50-mg dose without LD (n=191; mean age 33.2 years, 56 percent female). [WCD 2023, LB03]

Mean duration of AA since diagnosis was similar between the LD and no-LD groups (10.1 and 9.8 years), as was the mean duration of current AA episode (3.2 and 3.3 years).

“We had patients with severe AA,” noted Dr Melissa Piliang from the Cleveland Clinic in Ohio, US, at WCD 2023. Nearly half (46 percent) of the cohort had alopecia totalis/alopecia universalis (AT/AU). Mean SALT* scores at baseline were about 90 (overall cohort) and 82 (non-AT/AU subgroup).

Dr Melissa Piliang discussing the findings at WCD 2023.

Many patients also had eyebrow and eyelash involvement. More than 80 percent of participants had abnormal EBA** score, while about three-quarters had abnormal ELA** score.

“SALT ≤20 scores were very good at month 24. Patients with LD responded quicker, but by month 24, both groups achieved this endpoint,” said Piliang.

At month 12, more than half of participants with LD achieved SALT ≤20; by month 24, this increased to 58 percent. For those without LD, the corresponding 12- and 24-month rates were 45 percent and 62 percent, respectively. Looking at the 2-year rates, it appears that patients who did not have LD had better responses than those who had, noted Piliang.

“We still had very good numbers for SALT ≤10,” she continued. About half of participants with and without LD (47 percent and 51 percent) achieved this endpoint at month 24. The corresponding 12-month rates were 44 percent and 34 percent. “Again, patients with LD had a quicker response but those without LD caught up by month 24,” Piliang added.

“Looking at patient-reported outcomes, patients were very happy with the medication that by the end of year 2, around 70 percent had met the PGI-C criteria of ‘moderately improved’ or ‘greatly improved’,” said Piliang. Those with LD initially had higher PGI-C*** response than those without (72 percent vs 62 percent at 12 months). She said this was expected because they had a more rapid response compared with those who did not receive LD.

Eyebrow and eyelash responses were also good. At month 24, more than half of participants in the LD and no-LD groups (56 percent and 61 percent) had EBA responses. For ELA, the corresponding rates were 60 percent and 52 percent. Of note, compared with the other endpoints, patients with LD did not respond faster in terms of EBA and ELA outcomes.

Adverse event (AE) rate was lower in the LD vs the no-LD group (82 percent vs 93 percent), but rates of serious AEs were similar (5 percent vs 4 percent). Acne was one of the most common AEs (>10 percent), which is a common side effect of JAK inhibitors, noted Piliang.

Overall, there were few serious infections (1 percent) and cases of reactivation of herpes zoster and herpes simplex (about 2 percent for both). No opportunistic infections were reported.

Meaningful, sustained efficacy

“The proportion of patients with response based on scalp, eyebrow, and eyelash hair regrowth increased over time to month 24. The PGI-C increased over time to month 12 and was consistent through month 24,” said Piliang. Ritlecitinib was well tolerated over 2 years, with a safety profile that aligned with the primary findings from the ALLEGRO phase IIb/III study.

“In summary, ritlecitinib 50 mg with or without the 200-mg LD demonstrated clinically meaningful and sustained long-term clinician- and patient-reported efficacy over 24 months in patients ≥12 years with AA,” Piliang concluded.

ALLEGRO-LT is underway. Further assessments at later timepoints shall provide long-term data.