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General Information
Litfulo (ritlecitinib) is a kinase inhibitor.
Litfulo is specifically indicated for the treatment of severe alopecia areata in adults and adolescents 12 years and older.
Litfulo is supplied as capsules for oral administration.
Dosing/Administration
Prior to Litfulo initiation:
- Tuberculosis (TB) infection evaluation: Litfulo initiation is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk for TB, start preventive therapy for latent TB prior to initiation of Litfulo.
- Viral hepatitis screening in accordance with clinical guidelines: Litfulo initiation is not recommended in patients with hepatitis B or hepatitis C.
- Treatment with Litfulo should not be initiated in patients with an absolute lymphocyte count (ALC) <500/mm3 or a platelet count <100,000/mm3.
- Update immunizations according to current immunization guidelines.
The recommended dosage of Litfulo is 50 mg orally once daily with or without food. Swallow capsules whole. Do not crush, split, or chew capsules. If a dose is missed, administer the dose as soon as possible unless it is less than 8 hours before the next dose, in which case, skip the missed dose. Thereafter, resume dosing at the regular scheduled time.
Mechanism of Action
Ritlecitinib irreversibly inhibits Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family by blocking the adenosine triphosphate (ATP) binding site. In cellular settings, ritlecitinib inhibits cytokine induced STAT phosphorylation mediated by JAK3-dependent receptors. Additionally, ritlecitinib inhibits signaling of immune receptors dependent on TEC kinase family members. The relevance of inhibition of specific JAK or TEC family enzymes to therapeutic effectiveness is not currently known.
Side Effects
Adverse effects associated with the use of Litfulo may include, but are not limited to, the following:
- headache
- diarrhea
- acne
- rash
- urticaria
- folliculitis
- pyrexia
- atopic dermatitis
- dizziness
- blood creatine phosphokinase increased
- herpes zoster
- red blood cell count decreased
- stomatitis
The Litfulo drug label comes with the following Black Box Warning:
Increased risk of serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death, including tuberculosis (TB). Interrupt treatment if serious infection occurs until the infection is controlled. Litfulo should not be given to patients with active tuberculosis. Test for latent TB before and during therapy; start treating latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative, latent TB test. Monitor all patients for signs and symptoms of infection during and after treatment with Litfulo.
Higher rate of all-cause mortality, including sudden cardiovascular death with another Janus kinase inhibitor (JAK) vs. TNF blockers in rheumatoid arthritis (RA) patients. Litfulo is not approved for use in RA patients.
Malignancies were reported in patients treated with Litfulo. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients.
Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients.
Thrombosis has occurred in patients treated with Litfulo. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers.
Clinical Trial Results
The FDA approval of Litfulo was based on the ALLEGRO Phase 2b/3 trial, which enrolled 718 patients with 50% or more scalp hair loss as measured by the Severity of Alopecia Tool (SALT), evaluated the efficacy and safety of Litfulo at 118 sites in 18 countries. In this pivotal study, 23% of patients treated with Litfulo 50 mg had 80% or more scalp hair coverage (SALT≤20) after six months compared to 1.6% with placebo. The efficacy and safety of Litfulo were consistent between adolescents (12 through 17 years of age) and adults (18 years of age and older).
Approval Date: 2023-06-01
Company Name: Pfizer