Ritlecitinib

Ritlecitinib is an oral kinase inhibitor developed by Pfizer for the treatment of severe alopecia areata in adults and adolescents aged twelve years and older. Other indications include vitiligo, ulcerative colitis and Crohn's disease.

The main pathophysiological mechanism in alopecia areata is thought to be the loss of the immune privilege of the hair follicles. This means that the follicular epithelium has an antigenic effect. Overall, however, the pathogenesis is complex and the predisposition to the disease is polygenically inherited.

Ritlecitinib irreversibly and selectively inhibits Janus kinase(JAK 3) and the tyrosine kinase (TEC) expressed in hepatocellular carcinomas by blocking the adenosine triphosphate (ATP) binding site. This disrupts the signal transduction of cytokines and reduces the cytolytic activity of natural killer cells (NK cells) and CD8+ T cells. The signaling pathways mediated by Janus kinase 3 and tyrosine kinase TEC play an important role in the pathophysiology of alopecia areata.

Ritlecitinib blocks the steps that lead to hair loss. In a larger clinical study (n=164 people), 74 out of 164 people (45%) regrew their hair after one year, and 61% after two years. In 8 out of 10 people, the regrown scalp hair remained intact over a period of 1 to 2 years. The regrowth of eyebrow and eyelash hair also increased over a period of two years. Around 8 out of 10 people were satisfied with their hair growth after two years. The results show that ritlecitinib is effective and suitable for long-term use in people aged 12 years and older with alopecia areata (Piliang M et al. 2025).

Recurrences after discontinuation of therapy: Around a few weeks to 2-3 months after discontinuation of therapy, users report recurrences. This is reminiscent of the relapse curve for baritinib. With baritinib, there was no clinical deterioration within the first 4 weeks after discontinuation, but by week 8, 10-11% were already suffering, and after 3 years (152 weeks), >80% of patients were no longer able to observe any positive effects.

The recommended dose is 50 mg ritlecitinib once daily per os. Check platelets and lymphocytes before starting therapy and after 4 weeks.

Discontinue therapy if the absolute lymphocyte count is less than 0.5 × 103/mm3, discontinue if the platelet count is less than 50 × 103/mm3

Discontinue therapy in case of infections.

The most common and clinically relevant adverse drug reactions (ADRs) of ritlecitinib include:

• (serious) infections, especially of the upper respiratory tract
• reactivation of latent infections such as herpes zoster or viral hepatitis
• diarrhea
• acne
• urticaria
• folliculitis
• Thrombocytopenia, lymphocytopenia

An increased risk of malignant diseases and thromboembolism was observed with another Janus kinase inhibitor, tofacitinib. However, it is still unknown whether this correlation also applies to selective JAK3 inhibitors such as ritlecitinib. The benefits and risks of treatment with ritlecitinib should therefore be weighed up particularly strictly in patients with a malignant disease or an increased risk of thromboembolism.

Due to the immunosuppressive effect, all patients should be tested for tuberculosis before starting treatment with ritlecitinib (^Litfulo®). Ritlecitinib must not be used in patients with active tuberculosis. If latent tuberculosis is present, anti-tuberculosis therapy should be initiated before the use of ritlecitinib. If no tuberculosis is detected, but the risk of tuberculosis is still high, anti-tuberculosis therapy should be considered before using Litfulo.

All patients treated with ritlecitinib should be closely monitored for evidence of infection. If a serious or opportunistic infection occurs, the use of ritlecitinib should be discontinued and appropriate antimicrobial therapy initiated.

Ritlecitinib must not be used in:

• Hypersensitivity to the active substance
• Active, serious infections, especially tuberculosis
• Severe liver dysfunction
• Pregnancy and breastfeeding

There are many therapies for AA, but no systemic agent was approved until recently, when baricitinib (Janus kinase (JAK1 and JAK2 inhibitor) was approved by the FDA for the treatment of adult patients with severe AA.

JAK inhibitors (JAKibs) target the γc-cytokine and interferon-gamma (IFN-γ) signaling pathway, which is critical to the immunopathogenesis of AA and thus may reverse hair loss in AA.

Although JAKibs are emerging as a promising treatment modality for AA, the ideal JAKib has yet to be found as there is limited data on H-2-H (head-to-head) comparisons of JAK inhibitors in AA.

In addition, the effect achieved with JAKibs does not persist after discontinuation of treatment, with many studies showing a high relapse rate after treatment with tofacitinib and ruxolitinib. Furthermore, recent studies have hypothesized that JAK2 may cause significant side effects due to its ubiquitous expression in contrast to JAK1, which is associated with several major cytokine receptor families, and JAK3, which is exclusively associated with the γc cytokine receptor (Sardana K et al. 2023).

On June 23, 2023, ritlecitinib was approved in the USA for the treatment of severe alopecia areata in adults and adolescents aged 12 years and older. Ritlecitinib was approved in Japan on June 26, 2023 and in the EU in September 2023 for the treatment of alopecia areata (limited to difficult-to-treat cases with extensive hair loss).

The European Commission has approved ritlecitinib (^Litfulo®) for the treatment of severe alopecia areata in adults and adolescents aged 12 and over. However, German health insurance companies do not cover the costs of this approved preparation: § 34 SGB V excludes the assumption of costs for drugs to improve hair growth.

1. Blair HA (2023) .Ritlecitinib: First Approval. Drugs. 2023 Sep;83(14):1315-1321.
2. Chen LC et alk. (2025) Patient Considerations when Using Ritlecitinib for Alopecia Areata in Adolescents: Guidance for the Clinicians. Skin Appendage Disord 11:262-269
3. Hordinsky M et al. (2023) Efficacy and safety of ritlecitinib in adolescents with alopecia areata: Results from the ALLEGRO phase 2b/3 randomized, double-blind, placebo-controlled trial. Pediatr Dermatol 40:1003-1009.
4. King B et al. (2023) Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomized, double-blind, multicentre, phase 2b-3 trial. Lancet 401:1518-1529.
5. Piliang M et al. (2025) Efficacy and safety of the oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase IIb/III and long-term phase III clinical studies in alopecia areata. Br J Dermatol 192: 215-227
6. Sardana K et al. (2023) Which is the Ideal JAK Inhibitor for Alopecia Areata - Baricitinib, Tofacitinib, Ritlecitinib or Ifidancitinib - Revisiting the Immunomechanisms of the JAK Pathway. Indian Dermatol Online J 14:465-474.
7. Song CJ et al. (2025) A Review of JAK Inhibitors for Treatment of Alopecia Areata in the Military Health Care System. Mil Med 190:e67-e73.