Long-Term Safety and Efficacy of Ritlecitinib in Alopecia Areata: New Insights from ALLEGRO-LT Study

Alopecia areata (AA) is a chronic autoimmune condition characterized by non-scarring hair loss that can range from patchy hair loss to complete scalp, face and body hair loss. The condition affects approximately 2% of the global population and is associated with significant psychological distress.

While treatment options have historically been limited, emerging therapies targeting immune pathways are changing the treatment landscape. One such promising therapy is ritlecitinib, a selective inhibitor of JAK3 and TEC family kinases, which is the focus of the long-term ALLEGRO-LT phase 3 study.

Alopecia Areata and the Need for Effective Long-Term Treatment

·         Patients with alopecia totalis (AT) and alopecia universalis (AU), the most severe forms of AA, often show resistance to conventional treatments.

·         The immune-driven destruction of hair follicles involves the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, which plays a key role in activating autoreactive CD8+ T cells.

·         Ritlecitinib, a dual JAK3/TEC inhibitor, is currently the only FDA-approved treatment for both adolescents (≥12 years) and adults with severe AA.

·         The ALLEGRO-LT study is an ongoing phase 3, open-label trial evaluating the long-term safety and efficacy of ritlecitinib in patients with ≥25% scalp hair loss.

·         This study expands upon the earlier ALLEGRO-2b/3 trial, which demonstrated that 23% of patients on ritlecitinib achieved significant hair regrowth within 24 weeks with improvements continuing through 48 weeks.

·         The ALLEGRO-LT trial includes de novo patients (newly enrolled) and rollover patients (from previous ritlecitinib trials), providing a broader patient population.

Study Design and Patient Cohort

The de novo cohort analyzed in this study included 449 patients, all receiving a 200 mg daily (QD) loading dose for four weeks, followed by 50 mg QD maintenance therapy.

The study categorized patients based on the Severity of Alopecia Tool (SALT) score, measuring scalp hair loss in four categories: 25–<50%, 50–<75%, 75–<100%, and 100% scalp hair loss (AT/AU).

At baseline:

• 34.5% of patients had AT/AU (SALT 100)

• 73.5% had eyebrow loss, and 65.9% had eyelash loss

• The average duration of AA since diagnosis was 6.1 years

• 27.6% discontinued the study, primarily due to withdrawal, lack of efficacy or adverse events (AEs).

Efficacy Results: Significant and Sustained Hair Regrowth

At Month 24, ritlecitinib demonstrated sustained hair regrowth, particularly in patients with less extensive scalp hair loss at baseline.

Key findings include:

• 73.5% of observed patients achieved a SALT ≤20 response (≤20% scalp hair loss)

• 66.4% achieved a SALT ≤10 response (≤10% scalp hair loss)

• Highest response rates were seen in patients with 25–50% hair loss with 94.6% reaching SALT ≤20 and 84.8% achieving SALT ≤10

• Patients with AT/AU (SALT 100) had lower response rates (46.5% for SALT ≤20, 41.4% for SALT ≤10) but showed continued improvement beyond 48 weeks

Notably, over 60% of patients with eyebrow and eyelash involvement experienced significant regrowth, addressing a crucial cosmetic and functional concern for AA patients. 82.4% of participants reported moderate to great improvement in their condition using the Patient Global Impression of Change (PGI-C) score.

Safety Profile and Tolerability

Long-term safety data confirmed ritlecitinib’s generally favorable safety profile with most adverse events (AEs) being mild or moderate. Among 447 patients analyzed for safety:

• 86.1% reported at least one AE

• Most common AEs: Positive SARS-CoV-2 test (24.2%), headache (20.8%) and fever (13.0%)

• Serious AEs were low (4.9%), including four serious infections (0.9%)

• One death (0.2%) occurred due to breast cancer, unrelated to treatment

• Herpes zoster (1.3%) and herpes simplex (2.7%) cases were minimal

• No opportunistic infections or thromboembolic events were reported

These findings reinforce the long-term safety of ritlecitinib with no major safety concerns emerging after two years of continuous treatment.

Clinical Implications: Early Intervention and Personalized AA Treatment

The ALLEGRO-LT study provides compelling evidence that ritlecitinib is an effective long-term treatment for AA, particularly when initiated early in the disease course. The study supports key clinical strategies, including:

• Early treatment initiation to maximize regrowth potential and prevent extensive hair loss

• Long-term therapy for sustained benefit, particularly in severe cases like AT/AU

• Addressing eyebrow and eyelash involvement, which significantly impacts quality of life

Key Insights:

The ALLEGRO-LT study establishes ritlecitinib as a durable and effective treatment for AA, with a strong safety profile and significant hair regrowth outcomes over 24 months. While patients with extensive hair loss (AT/AU) may require longer treatment durations, early intervention leads to higher response rates. These results reinforce ritlecitinib’s role as a cornerstone therapy for adolescents and adults with alopecia areata.

By - Eeshan Aggarwal

Reference:

Tziotzios C, Sinclair R, Lesiak A, Mehlis S, Kinoshita‐Ise M, Tsianakas A, Luo X, Law EH, Ishowo‐Adejumo R, Wolk R, Sadrarhami M. Long‐term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO‐LT phase 3, open‐label study. Journal of the European Academy of Dermatology and Venereology. 2025.