Smyraf (peficitinib) / Astellas, Maruho, Menarini - LARVOL DELTA

A retrospective chart review to explore the efficacy and safety of switching to peficitinib in Japanese patients with rheumatoid arthritis and inadequate response to biologic disease-modifying antirheumatic drugs. (PubMed, Mod Rheumatol) - "Peficitinib could be an effective treatment option for patients with RA refractory to bDMARDs."

Journal • Retrospective data • Immunology • Infectious Disease • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

The therapeutic potential for JAK inhibitors for immune-related adverse events from checkpoint inhibitors– a review of the literature (EULAR 2025) - "Background: Rheumatologists are well versed with T cell co-stimulation with abatacept, a CTLA-4 inhibitor being a licenced therapy for Rheumatoid Arthritis, Psoriatic Arthritis and Juvenile Idiopathic Arthritis...The four EMA licenced JAK inhibitors (Tofacitinib, Baritinib, Upadacitinib and Filgotinib) were included in addition to Peficitinib. The checkpoint inhibitors that were included within the search were Ipilumab, Tremeliumab, Nivolumab, Pemrbolizumab, Atezolizumab, Avelumab, Durvalumab, Cempilumab and Dostraliumab...3 (4%) of patients received baricitinib whilst 1 (1%) patient received 15mg Upadacitinib daily...Pembrolizumab monotherapy represented the most common ICI therapeutic choice, given to 9 (11%) patients, with other patients receiving ipilimumab/nivolimuman (5%), cambrelizumab (8%) and sintilimab (3%)...Across all patients, 41 (51%) patients received intravenous immunoglobulin (IVIG) with small proportion of patients receiving infliximab (8%) and/or..."

Adverse events • Checkpoint inhibition • Review • Endocrine Disorders • Gastric Cancer • Gastroenterology • Gastrointestinal Disorder • Hepatocellular Cancer • Hepatology • Idiopathic Arthritis • Immunology • Infectious Disease • Inflammatory Arthritis • Liver Cancer • Lung Cancer • Myositis • Oncology • Pneumonia • Psoriasis • Psoriatic Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Solid Tumor • IL6

THE EFFECTS OF GLUCOCORTICOID ON TREATMENT COURSE IN PATIENTS WITH DIFFICULT TO TREAT RHEUMATOID ARTHRITIS (EULAR 2025) - "Inability to taper glucocorticoids (below 7.5 mg/day prednisone or equivalent) was included in the EULAR definition of D2TRA...In these 673 patients, 137 patients met D2TRA criteria (tocilizumab: n=21, sarilumab: n=10, abatacept: n=31, tofacitinib: n=30, baricitinib: n=30, Upadacitinib: n=10, peficitinib: n=4, filgotinib: n=1)...In the logistic regres-sion analysis, ORs were adjusted for age, sex, body mass index, disease durations, titer of rheumatoid factor, titer of antibodies against cyclic citrullinated peptide, DAS-ESR, HAQ, methotrexate dose, glucocorticoid dose, type of bDMARDs/JAKi, number of past bDMARDs/JAKi, history of lymphoproliferative disorders, history of pancytopenia and history of interstitial pneumonia based on the results of the univariate analysis and general risk factors of inability to taper glucocorticoid... Drug retention rate and clinical efficacy of D2TRA patients were not different between glucocorticoid use group and glucocorticoid non-use..."

Clinical • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

COMPARATIVE EFFECTIVENESS OF UPADACITINIB VERSUS OTHER JAK INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A GLOBAL REAL-WORLD SETTING (EULAR 2025) - "Objectives: We assessed the effectiveness of UPA vs other JAKis, including tofacitinib, baricitinib, and peficitinib, using real-world data. The findings of this real-world study of patients with RA demonstrate that greater proportions of patients attained physician-reported DAS28 remission, absence of pain, and medication adherence with UPA vs other JAKis."

Clinical • HEOR • Real-world • Real-world evidence • Fatigue • Immunology • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology

IMPACT OF AUTOANTIBODY STATUS ON THE LONG-TERM EFFICACY AND RETENTION RATES OF JAK INHIBITORS: INSIGHTS FROM A COMPARATIVE STUDY OF FIVE JAK INHIBITORS (EULAR 2025) - "Patients were categorized based on the JAK inhibitor: tofacitinib (TOFA, n=57), baricitinib (BARI, n=64), upadacitinib (UPA, n=73), peficitinib (PEFI, n=28), and filgotinib (FIL, n=29). This study highlights differences in efficacy and retention rates among the five JAK inhibitors, with a focus on autoantibody status. UPA showed superior retention rates and efficacy, particularly in seronegative patients, aligning with its indication for psoriatic arthritis. These findings underscore the importance of considering autoantibody status when selecting JAK inhibitors for RA management."

Clinical • Immunology • Inflammatory Arthritis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies

PERIOPERATIVE DISCONTINUANCE PERIOD OF JANUS KINASE INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO UNDERWENT ORTHOPAEDIC JOINT SURGERY (EULAR 2025) - "The medications used were tofacitinib in 11 surgeries, baricitinib in 11 surgeries, upadacitinib in 9 surgeries, filgotinib in 4 surgeries, and peficitinib in 1 surgery. Flare-ups of RA symptoms during JAKi discontinuation were observed in 25% of the cases, with longer preoperative discontinuation periods and higher preoperative disease activity associated with flare-ups. From these results, preoperative disease activity should be well controlled to prevent flare-ups of RA symptoms, even in patients undergoing surgery while using JAKi. On the other hand, the incidence rate of SSI was 8.3%, which is higher than the general infection rate for clean orthopedic surgeries (0.5–2%)."

Clinical • Surgery • Anesthesia • Immunology • Infectious Disease • Inflammatory Arthritis • Musculoskeletal Diseases • Orthopedics • Pain • Rheumatoid Arthritis • Rheumatology

ASSOCIATION BETWEEN TYPES OF JAK INHIBITORS AND THE RISK OF HERPES ZOSTER IN ELDERLY RHEUMATOID ARTHRITIS PATIENTS AGED 75 YEARS AND OLDER (EULAR 2025) - "The cohort included tofacitinib (145 [12%]), baricitinib (524 [45%]), peficitinib (91 [8%]), Upadacitinib (217 [19%]), and filgotinib (186 [16%]). In this real-world data for elderly RA patients aged 75 years and older treated, filgotinib did not demonstrate a significant benefit over other JAK inhibitors in reducing the risk of HZ. The observed advantage of filgotinib in previous network meta-analyses may be influenced by biases in the target population."

Clinical • Chronic Kidney Disease • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Nephrology • Neuralgia • Pain • Renal Disease • Rheumatoid Arthritis • Rheumatology • Varicella Zoster

JAK-STAT inhibitors in noninfectious uveitis - A review. (PubMed, Indian J Ophthalmol) - "However, a certain subset of NIU patients does not respond to conventional IMT therapy, such as methotrexate and azathioprine...One such example is the use of TNF-α inhibitors, such as adalimumab and infliximab...JAK-STAT inhibitors, such as tofacitinib, baricitinib, upadacitinib, peficitinib, delgocitinib, and filgotinib have been FDA-approved for use in autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and inflammatory bowel disease. The available literature suggests the potential efficacy of these drugs in controlling uveitic inflammation; however, their use in NIU is still under investigation, with no randomized controlled trials providing Level I evidence."

Journal • Review • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Ocular Inflammation • Ophthalmology • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • Ulcerative Colitis • Uveitis • IL12A • IL17A • IL23A • IL6

A Case of Rheumatoid Meningitis with Generalized Convulsions during Peficitinib Treatment, in which Anti-cyclic Citrullinated Peptide Antibody in the Cerebrospinal Fluid Was Useful for Making a Diagnosis: A Review of the Literature and Previous Reports. (PubMed, Intern Med) - "RM is often diagnosed using a meningeal biopsy and MRI; however, recent reports have suggested that the CSF ACPA titers (antibody titer index) may also be elevated. In this case, CSF ACPA was useful for making a diagnosis and selecting the optimal treatment modality."

Journal • CNS Disorders • Epilepsy • Immunology • Infectious Disease • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Janus kinase inhibitors and the risk of infections: a network meta-analysis across disease indications. (PubMed, Expert Opin Drug Saf) - "To compare the risks of serious infections, herpes zoster (HZ), and opportunistic infections associated with Janus kinase (JAK) inhibitors versus placebo, tumor necrosis factor-α inhibitors (TNFi), methotrexate (MTX), and among different JAK inhibitors...Similarly, tofacitinib (10 mg), baricitinib (4 mg), upadacitinib (15 mg, 30 mg), abrocitinib (200 mg), and peficitinib (100 mg) showed a significantly different risk of HZ infection compared to placebo...Future long-term studies should be conducted. : CRD42024523067."

Journal • Retrospective data • Review • Herpes Zoster • Infectious Disease • Oncology • Varicella Zoster

Pharmacological Management of Psoriasis: Current Landscape and Future Perspectives. (PubMed, Recent Adv Inflamm Allergy Drug Discov) - "Numerous novel synthetic agents, such as JAK/STAT inhibitors [ruxolitinib, peficitinib], TYK2 inhibitors [zasocitinib, ropsacitinib], RORꝩT inhibitors [cedirogant], A3AR agonists [piclodenoson], and CXCR2 antagonists [vimnerixin] are undergoing extensive clinical trials and have demonstrated beneficial outcomes in multiple phases of these trials. Deucravacitinib, an orally administered TYK2 inhibitor, has recently received FDA approval for the treatment of moderate to severe plaque psoriasis...Moreover, these pathways can be exploited to personalize anti-psoriatic therapy, minimize side effects, and maximize therapeutic outcomes. Altogether, the integration of biological agents and synthetic agents can overcome the challenges associated with the management of the repertoire of psoriatic pathophysiology and symptoms."

Journal • Dermatology • Immunology • Inflammation • Psoriasis • CXCR2 • IL23A • TYK2

Comparison of anti-inflammatory and anti-angiogenic effects of JAK inhibitors in IL-6 and TNFα-stimulated fibroblast-like synoviocytes derived from patients with RA. (PubMed, Sci Rep) - "In this study, we compared the inhibitory effects of five JAK inhibitors, including tofacitinib (TOF), baricitinib, peficitinib, upadacitinib, and filgotinib, on interleukin (IL)-6-induced inflammation in RA synovial tissues. All five inhibitors effectively suppressed IL-6-induced inflammatory and angiogenic factors, including vascular endothelial growth factor, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, by inhibiting the phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3. Overall, the results suggest that while all five JAK inhibitors are effective in reducing IL-6-induced inflammatory and angiogenic factors, their efficacy may differ owing to specific molecular mechanisms and pharmacological properties."

Clinical • Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • ICAM1 • IL6 • STAT1 • STAT3 • TNFA • VCAM1

Comparative Efficacy and Safety of JAK Inhibitors in the Management of Rheumatoid Arthritis: A Network Meta-Analysis. (PubMed, Pharmaceuticals (Basel)) - "This NMA's results indicate that commercially available JAKinibs show superior ACR responses and have comparable tolerability to placebo."

Clinical • Journal • Retrospective data • Review • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Varicella Zoster

Efficacy and safety of first-line targeted synthetic DMARDs in rheumatoid arthritis patients with chronic kidney disease. (PubMed, Rheumatology (Oxford)) - "tsDMARDs have demonstrated efficacy and safety in patients with RA and CKD; however, clinicians should consider the potential for herpes zoster and DVT in patients with eGFR <30 mL/min/1.73 m2."

Journal • Cardiovascular • Chronic Kidney Disease • Gastrointestinal Disorder • Hematological Disorders • Herpes Zoster • Immunology • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatoid Arthritis • Rheumatology • Thrombosis • Varicella Zoster • CRP

TFAP2A Activates ADAM8 to Promote Lung Adenocarcinoma Angiogenesis Through the JAK/STAT Signaling Pathway. (PubMed, J Biochem Mol Toxicol) - "The JAK inhibitor Peficitinib reversed the proangiogenic effects induced by ADAM8 overexpression...This study reveals for the first time the critical role of ADAM8 in LUAD angiogenesis, demonstrating that TFAP2A promotes JAK/STAT pathway conduction by activating ADAM8. This finding not only provides a new perspective for understanding the pathogenesis of LUAD but also lays the foundation for the development of new therapies targeting ADAM8."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ADAM8 • TFAP2A

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling. (PubMed, Sci China Life Sci) - "The potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2 (TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT (especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT."

Journal • Giant Cell Tumor of Bone • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • Tenosynovial Giant Cell Tumor • TYK2

Direct reprogramming of human fibroblasts into hair-inducing dermal papilla cell-like cells by a single small molecule. (PubMed, Biochem Pharmacol) - "In the initial screening, five candidate small molecules were identified from a pool of 1,817 compounds, and the small molecule peficitinib was further identified by the further hair follicle regeneration experiments...Furthermore, transcriptome analysis showed that the wingless/integrated (Wnt) signaling pathway and the transforming growth factor β (TGF-β) signaling pathway, both of which play crucial roles in hair follicle morphogenesis, are upregulated and enriched in these DPC-LCs. These functional DPC-LCs offer a promising avenue for obtaining a plentiful supply of hair-inducing cells, thereby advancing the development of therapeutic strategies for hair loss treatment."

Journal • Alopecia • TGFB1

Risk of Malignancy Under the Treatments with Janus Kinase Inhibitors in Patients with Rheumatoid Arthritis: An Analysis Using Japanese Health Insurance Database (ACR Convergence 2024) - "The purpose of this study was to compare the risk of malignancy among JAKIs users, biological disease-modifying antirheumatic drugs (bDMARDs) (tumor necrosis factor inhibitors [TNFIs] and non-TNFIs) users, and methotrexate (MTX) users in patients with rheumatoid arthritis (RA) using a large health insurance claims data in Japan. This retrospective longitudinal population-based study was conducted using claims data provided by Medical Data Vision Co., Ltd (Tokyo, Japan). We defined individuals as new users of JAKIs (tofacitinib, baricitinib, peficitinib, upadacitinib, and filgotinib), bDMARDs or MTX if they met all of the following: 1) having at least one ICD10 code, M05 or M06; 2) having at least one prescription of JAKI, bDMARDs, or MTX between July 2013 and July 2020; 3) being over 18 years old; and 4) having prescription of neither JAKIs, bDMARDs nor MTX prior to six months before the index month (i.e., baseline period)... JAKIs user had a significantly higher risk of..."

Clinical • Reimbursement • US reimbursement • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Comparative Effectiveness of Upadacitinib versus Other JAK Inhibitors in Patients with Rheumatoid Arthritis in a Global Real-World Setting (ACR Convergence 2024) - "Here, we assessed the effectiveness of UPA vs other JAKis, including tofacitinib, baricitinib, and peficitinib, using real-world data. Data were extracted from the Adelphi RA Disease-Specific Programme, a cross-sectional study with elements of retrospective data collection. The findings of this real-world study of patients with RA demonstrate that greater proportions of patients attained physician-reported DAS28 remission, absence of pain, and medication adherence with UPA vs other JAKis."

Clinical • HEOR • Real-world • Real-world evidence • Fatigue • Immunology • Inflammatory Arthritis • Pain • Rheumatoid Arthritis • Rheumatology

A Study to Continue ASP015K Treatment to Rheumatoid Arthritis Patients Who Completed Phase IIb Study or Phase III Study of ASP015K (clinicaltrials.gov) - P3 | N=843 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2b ➔ P3

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Drug Interaction Study to Evaluate the Pharmacokinetics of ASP015K and Methotrexate in Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P1b ➔ P1

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Evaluate the Efficacy and Safety of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects (clinicaltrials.gov) - P2 | N=281 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2b ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=289 | Completed | Sponsor: Astellas Pharma Global Development, Inc. | Phase classification: P2b ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study to Evaluate the Safety and Efficacy of ASP015K in Moderate to Severe Rheumatoid Arthritis Subjects Who Have Had an Inadequate Response to Methotrexate (clinicaltrials.gov) - P2 | N=379 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2b ➔ P2

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

A Study to Explore Efficacy and Safety of ASP015K in Subjects With Moderate to Severe Psoriasis (clinicaltrials.gov) - P2 | N=124 | Completed | Sponsor: Astellas Pharma Inc | Phase classification: P2a ➔ P2

Phase classification • Dermatology • Immunology • Psoriasis