Litfulo (ritlecitinib) / Pfizer - LARVOL DELTA

Comment on "Efficacy and Safety of Zimlovisertib, Ritlecitinib and Tofacitinib, Alone and in Combination, in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate". (PubMed, Arthritis Rheumatol) - No abstract available

Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Intermittent Low-dose Ritlecitinib in Refractory Paediatric Alopecia Areata: A Case Report with Therapeutic Implications. (PubMed, Acta Derm Venereol) - No abstract available

Journal • Alopecia • Immunology • Pediatrics

A 104-Week Study of Ritlecitinib Oral Capsules in Adults With Nonsegmental Vitiligo (Active and Stable) Tranquillo 2 (clinicaltrials.gov) - P3 | N=1201 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Dermatology • Immunology • Vitiligo

Patient Considerations when Using Ritlecitinib for Alopecia Areata in Adolescents: Guidance for the Clinicians. (PubMed, Skin Appendage Disord) - "The ALLEGRO phase 2b-3 trial demonstrated that 25% and 50% of adolescents with a Severity of Alopecia Tool (SALT) score ≥50 at baseline achieved a SALT score ≤20 at week 24 and week 48 after receiving 50 mg ritlecitinib daily, respectively. This review summarizes the mechanism of action, clinical trial evidence on efficacy and safety profile, factors associated with treatment response to JAK inhibitors for AA, and vaccination considerations for adolescents. This review aims to facilitate the risk-benefit assessment and shared decision-making between clinicians and patients and provide clinical considerations and management recommendations for ritlecitinib use in adolescents with AA."

Journal • Review • Acne Vulgaris • Alopecia • Hepatocellular Cancer • Immunology • Infectious Disease • Oncology • Pain • Solid Tumor

Orally effective FDA-approved protein kinase targeted covalent inhibitors (TCIs): A 2025 update. (PubMed, Pharmacol Res) - "The clinical efficacy of ibrutinib, a Bruton tyrosine kinase blocker, in the treatment of mantle cell lymphoma following its 2013 approval helped to overcome a general bias against the development of irreversible drug inhibitors. Other approved targeted covalent inhibitors include acalabrutinib and zanubrutinib, which also block Bruton tyrosine kinase. Afatinib, dacomitinib, lazertinib, mobocertinib, and osimertinib inhibit members of the epidermal growth factor receptor family (ErbB1/2/3/4) and are used in the treatment of non-small cell lung cancers. Neratinib inhibits ErbB2 and is used in the management of ErbB2/HER2-positive breast cancer. Futibatinib blocks the fibroblast growth factor receptor family and is prescribed for the treatment of cholangiocarcinoma while ritlecitinib, which inhibits JAK3, is used in the management of alopecia areata. The eleven drugs considered in this review have a common mechanism of action involving the addition of a protein cysteine..."

FDA event • Journal • Review • Alopecia • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Lung Cancer • Lymphoma • Mantle Cell Lymphoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BTK • EGFR • FGFR

Janus kinase inhibitors for alopecia areata: a review of clinical data. (PubMed, Front Immunol) - "Studies have shown that JAK inhibitors exhibited good efficacy and safety in the treatment of AA, with fewer serious side effects. This article reviews the mechanism of action of JAK inhibitors in the treatment of AA and the effects and side effects of representative drugs."

Clinical data • Journal • Review • Alopecia • Immunology • CD8

Alopecia areata and ritlecitinib: Unravelling response trajectories. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal • Alopecia • Immunology

Strong efficacy of ritlecitinib 50 mg and baricitinib 4 mg in alopecia areata, but further research needed to establish superiority. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Head-to-Head • Journal • Alopecia • Immunology

Unravelling the role of JAK3/TEC kinase signalling with ritlecitinib in alopecia areata lesional skin and alopecia areata-induced human hair follicles ex vivo (SID 2025) - "Thus, JAK3/TEC signalling is active in lesional AA skin and can be inhibited by ritlecitinib treatment. This, together with the ability of ritlecitinib to interfere with αCD3/αCD28+IL-2-induced perifollicular T-cell expansion and HF immune privilege collapse in HFs ex vivo, highlights the clinical mechanism by which JAK3/TEC inhibition reduces symptoms of AA."

IO biomarker • Preclinical • Alopecia • Immunology • CD8 • FASLG • GZMA • GZMB • IFNG • IL2 • IRF4 • JAK3 • STAT6

Effects of JAK/STAT inhibitors in cutaneous T-cell lymphoma cells (SID 2025) - "Four JAK inhibitors were tested: Abrocitinib (JAK1), Tofacitinib (pan-JAK, potent JAK3 inhibition), Ritlecitinib (JAK3), and Brepocitinib (pan-JAK, potent TYK2/JAK1 inhibition). Notably, Tofacitinib combined with AS1517499 or TTI-101 showed synergistic apoptotic effects, as did the combination of the two STAT inhibitors. These findings underscore the efficacy of JAK/ STAT inhibitors in MJ and HuT 78 cells, highlight differential sensitivities between the cell lines, and support ongoing investigations into the underlying mechanisms."

Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • JAK1 • JAK3 • STAT3 • STAT6 • TYK2

Jak inhibitor intraclass switch in alopecia areata patients: A retrospective review of cases at an academic center (SID 2025) - "Baricitinib and Ritlecitinib are JAKi approved for the treatment of AA. In our cohort, most patients had reached a treatment plateau and following intraclass switch were able to obtain significant improvement in SALT scores. This study is limited by its small sample-size and retrospective nature; however, we have shown positive results in hair growth after intraclass switch."

Retrospective data • Review • Acne Vulgaris • Alopecia • Dermatology • Immunology • Inflammation

JAK inhibitor halts the progression of acute exacerbation of alopecia areata (SID 2025) - "JAKI, including baricitinib (Olumiant) and ritlecitinib (Litfulo), have demonstrated success in treating chronic AA with extensive hair loss. While this study suggests that early baricitinib intervention may modify the disease course by rapidly halting hair shedding and promoting regrowth, limitations such as the small sample size, and short follow-up duration warrant further investigation. Future studies should evaluate the broader efficacy of JAKIs in managing acute AA."

Alopecia • Immunology

SYMPTOM RESPONSE TRAJECTORY ANALYSIS IDENTIFIES DISTINCT SUBPOPULATIONS IN MODERATE-TO-SEVERE ULCERATIVE COLITIS LINKED TO MAINTENANCE OUTCOMES: A PATIENT LEVEL POST-HOC ANALYSIS OF 2,378 PARTICIPANTS ACROSS 6 RCT'S WITH 8 ADVANCED THERAPIES (DDW 2025) - "Posthoc analysis of the SELECTION trial (filgotinib) demonstrated that analysis of daily PRO2 scores (stool frequency/rectal bleeding) as time-series data reveals discrete subpopulations...Methods In a cross-industry/academia collaboration, data from 2,378 UC participants from RCTs of adalimumab, brepocitinib, etrasimod, etrolizumab, ozanimod, ritlecitinib, ustekinumab, and vedolizumab in UC were analyzed for PRO2-based treatment symptom response trajectories using group-based trajectory modeling (GBTM)...Symptom response trajectories may reflect underlying heterogeneity in individual disease biology in interaction with different MOA (i.e. endotypes). RNASeq analysis of transcriptome regulation in these patients aims to further explore this hypothesis."

Clinical • Metastases • Retrospective data • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

A Cost Per Responder Analysis of Ritlecitinib and Baricitinib: Assessing the Impact of Clinical Efficacy and Dosing Variability on Overall Treatment Costs of Severe Alopecia Areata (AA) (ISPOR 2025) - "Ritlecitinib is more cost-effective per responder than baricitinib at Weeks 24 and 52. These findings support reimbursement or formulary inclusion of ritlecitinib for the treatment of AA. Given the modelling approach, results may be sensitive to response assessment timepoints and up-titration timing, which may vary in clinical practice."

Clinical • HEOR • Treatment costs • Alopecia • Immunology

SALT score distribution with ritlecitinib treatment up to 24 months in alopecia areata. (PubMed, J Eur Acad Dermatol Venereol) - No abstract available

Journal • Alopecia • Immunology

Paradoxical Activation of Entheseal Myeloid Cells by JAK1 and TYK2 Inhibitors via IL10 Antagonism. (PubMed, Arthritis Rheumatol) - "These findings help explain the emergent efficacy of TYK2 blockade in SpA spectrum related arthritis that is not IL-10 dependent but indicates why such strategies may not be a panacea for SpA spectrum disorder related intestinal inflammation."

Journal • Ankylosing Spondylitis • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Rheumatology • Seronegative Spondyloarthropathies • Spondylarthritis • Ulcerative Colitis • IFNG • IL10 • IL17A • IL1B • IL23A • JAK1 • JAK2 • JAK3 • TLR4 • TNFA • TYK2

Comprehensive Safety Exposure-Response Analysis to Support Ritlecitinib Dose Selection. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Covariate analysis within each model indicated that the safety ER relationship of ritlecitinib is similar across all the patient subgroups and no unique safety risks associated with ritlecitinib are anticipated in adolescent patients. Therefore, this comprehensive safety ER analysis supported the selection of the ritlecitinib 50 mg non-loading dose regimen for AA patients including both adults and adolescents."

Journal • Alopecia • Immunology • Infectious Disease

SERUM ECM BIOMARKERS CORRELATE WITH ENDOSCOPIC RESPONSE TO RITLECITINIB IN PHASE-2 STUDIES OF UC AND CD (DDW 2025) - "These preliminary data suggest that serum biomarkers for mucosal damage and neutrophil activation could be used to assess disease activity/severity in response to ritlecitinib treatment. This highlights the potential of circulating ECM biomarkers as predictors of clinical response in Crohn's disease."

Biomarker • P2 data • Crohn's disease • Fibrosis • Gastroenterology • Inflammatory Bowel Disease • JAK3

ALLEGRO-100: A Study of 2 Doses of Ritlecitinib in People 12 Years of Age and Older With Alopecia Areata (clinicaltrials.gov) - P3 | N=550 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Alopecia • Dermatology • Immunology

Drug-drug interaction profile of ritlecitinib as perpetrator and victim through cytochrome P450. (PubMed, Br J Clin Pharmacol) - "Ritlecitinib is a moderate inhibitor of CYP3A and CYP1A2. Strong CYP inducers can reduce ritlecitinib concentrations, but not to clinically relevant levels leading to lack of benefit."

Journal • CYP1A2 • JAK3

Selective JAK Inhibition Ameliorates Aire Deficiency–Driven Autoimmunity (CIS 2025) - "Aire KO mice underwent treatment with three selective JAK inhibitors: JAK1i (itacitinib), JAK2i (CEP-33779), and JAK3i (ritlecitinib). We show that JAK1- and JAK2-selective inhibition led to a similarly effective amelioration of IFNg-driven inflammation and tissue injury compared with the JAK1/2 inhibitor, ruxolitinib, in Aire KO mice. By contrast, although JAK3 inhibition markedly decreased lymphocytic accumulation in Aire KO mice, it appeared less effective in reducing IFNg-driven inflammation and tissue injury compared with all other tested JAK inhibitors. Our study sheds light on the differential roles of JAK inhibitors in the context of APECED-associated autoimmunity and informs future work that may help develop more selective JAK inhibitor-based treatments in APECED patients with the goal to achieve maximal efficacy and long-term safety."

Candidiasis • Immunology • Inflammation • AIRE • CD4 • CD8 • CXCL9 • IFNG • JAK3

Ritlecitinib in Clinical Practice: A Real-World Study of Efficacy, Safety, and Prior JAK Inhibitor Impact in Alopecia Areata. (PubMed, Clin Exp Dermatol) - No abstract available

Journal • Real-world evidence • Alopecia • Immunology

Ritlecitinib in CTCL (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Recruiting ➔ Active, not recruiting | N=20 ➔ 7 | Trial completion date: Apr 2026 ➔ Jun 2025 | Trial primary completion date: Apr 2026 ➔ Jan 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • TNFRSF8

An Asymmetric Reductive Amination Synthesis of Ritlecitinib Using (S)-α-Methylbenzylamine as Chiral Auxiliary. (PubMed, Chemistry) - "This lactam is converted to ritlecitinib via a five-step sequence in 62% overall yield. This approach effectively circumvents the use of precious metal catalysts or hazardous reagents for constructing the chiral piperidine moiety, which were essential components in prior synthetic route."

Journal

JAK Inhibitors and Inflammatory Nail Disorders: A Systematic Review of Clinical Outcomes and Therapeutic Potential. (PubMed, Am J Clin Dermatol) - "This review highlights Janus kinase/Tyrosine kinase 2 inhibitors as a valuable addition to the therapeutic arsenal for inflammatory nail disorders while emphasizing the importance of safety assessments and tailored treatment approaches. The long-term safety of Janus kinase/Tyrosine kinase 2 inhibitors still needs further investigation and the potential for adverse events emphasizes the need for tailored therapeutic strategies, including more studies on topical formulations."

Clinical data • Journal • Review • Infectious Disease • Inflammation • TYK2