What You Should Know About Ritlecitinib

Alopecia areata (AA) is an autoimmune disease characterized by sudden hair loss that can occur in patches and may lead to complete scalp and body hair loss. JAK inhibitors have emerged as a groundbreaking treatment for severe AA, representing the first FDA-approved therapeutic options for individuals facing this disease.¹ Among these, ritlecitinib stands out as the only therapy indicated to treat severe AA in both adults and adolescents 12 years and older,² marking a significant advancement in the management of severe AA for younger patients.

Mechanism of Action of Ritlecitinib
Ritlecitinib is a Janus kinase (JAK) inhibitor that permanently blocks JAK3 and tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinases at their adenosine triphosphate (ATP) binding sites, lowering immune activity.² This targeted action stops specific signaling pathways in immune cells, reducing T cell activity,² which is important for directly blocking the pathways responsible for reacting to hair follicles, a key cause of hair loss in AA. By focusing on JAK3 and TEC kinases, ritlecitinib specifically targets the immune system's attack on hair follicles, reducing this response without broadly suppressing the entire immune system.² This targeted inhibition helps promote hair regrowth and may reduce the side effects that come with less-selective JAK inhibitors.²

Prescribing Considerations
Ritlecitinib is an oral medication used to treat alopecia areata prescribed to adults and children 12 years and older, with a standard dosage of 50 mg taken once daily.² Ritlecitinib comes with a boxed warning due to an increased risk of serious infections, including bacterial, fungal, viral, and opportunistic infections, which may lead to hospitalization or death.² It is recommended that patients be tested for latent tuberculosis (TB) before and during treatment, and any active infection should be managed before starting ritlecitinib.² Additionally, there are increased risks of all-cause mortality, including sudden cardiovascular events, for patients also using another JAK inhibitor vs TNF blockers. Patients should be counseled on the chance of thrombotic events, including pulmonary embolism and venous and arterial thrombosis, with another JAK inhibitor vs TNF blockers.² While many patients experience mild or no side effects, some common side effects include headache, diarrhea, and acne.² 

In the randomized controlled ALLEGRO trial, ritlecitinib demonstrated a meaningful response in reducing hair loss compared to placebo.¹ In this trial, 31% of patients on a 200 mg + 50 mg regimen experienced a significant improvement compared to 2% on placebo.¹ Other dosing options, such as 200 mg + 30 mg, 50 mg, and 30 mg, also showed statistically significant improvements, with response rates of 22%, 23%, and 14%, respectively.¹ The trial underscored that the highest dose resulted in the most substantial response, with a 29.1% improvement over placebo (95% CI 21.2–37.9).¹

A post hoc analysis of the ALLEGRO phase 2b/3 trial evaluated the impact of continued ritlecitinib therapy on hair regrowth in patients with alopecia areata (AA).³ The results indicated that the majority of patients who demonstrated a clinical response by week 24, as assessed by a SALT score of ≤20 or other efficacy measures, maintained their improvements through week 48.³ Additionally, patients with more extensive hair loss and longer disease duration who did not meet the response criteria at week 24 showed significant clinical improvement with prolonged treatment, with up to one-third achieving target response criteria by week 48.³ More than 85% of patients who achieved a SALT score of ≤20 and more than 68% of patients who achieved a SALT score of ≤10 at week 24 sustained their response through week 48, and 52.4% to 96.9% of those with eyebrow (EBA) and eyelash (ELA) regrowth improvements at week 24 continued to show progress by week 48.³ Notably, some patients who had not met the response criteria by week 24 exhibited late responses, with 22.2% to 33.7% reaching a SALT score of ≤20 and 16.7% to 32.8% demonstrating meaningful improvements in EBA and ELA by week 48.³ These results show that ritlecitinib may provide continued benefits for AA patients, including those who initially do not respond to treatment by week 24.³

Improving Lives for Many AA Patients
AA can heavily impact quality of life, self-esteem, and mental health. A targeted treatment such as ritlecitinib can help offer a direct way to lessen hair loss by focusing specifically on the pathways involved in the immune response to hair follicles. For those with AA, having access to such treatments presents an opportunity to regain control, boost confidence, and improve overall well-being.

References:

1. King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial [published correction appears in Lancet. 2023 Jun 10;401(10392):1928. doi: 10.1016/S0140-6736(23)01078-4]. Lancet. 2023;401(10387):1518-1529. doi:10.1016/S0140-6736(23)00222-2
2. LITFULO. Prescribing Information. Pfizer; 2023
3. Piliang M, Lynde C, King B, et al. Sustained hair regrowth with continued ritlecitinib treatment through week 48 in patients with alopecia areata with or without early target responses: Post hoc analysis of the ALLEGRO phase 2b/3 trial. J Am Acad Dermatol. Published online October 17, 2024. doi:10.1016/j.jaad.2024.09.064