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

Understanding Cardiovascular Events With JAK Inhibitors: Similarities and Differences of the Vascular Effects Between Different JAK Inhibitors on Endothelial Cells Exposed to Inflammatory Cytokines. (PubMed, ACR Open Rheumatol) - "All JAKi reduced EC inflammation but most JAKi could not prevent the up-regulation of adhesion molecules or the increase in procoagulant and the decrease in anticoagulant factors triggered by proinflammatory cytokines. Peficitinib and fedratinib exhibited cytotoxic effects causing EC apoptosis."

Journal • Cardiovascular • Oncology • ANXA5 • CXCL8 • ICAM1 • IL17A • IL6 • TNFA • VCAM1

Janus Kinase Inhibitors During Pregnancy and Adverse Drug Reactions: A Pharmacovigilance Disproportionality Analysis in VigiBase. (PubMed, Clin Transl Sci) - "This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy-related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy."

Adverse drug reaction • Adverse events • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

High MDR1 expression in rheumatoid arthritis is associated with increased MMP-3 levels and use of bDMARDs: potential independence of JAK inhibitors from MDR1. (PubMed, Rheumatology (Oxford)) - "High MDR1 expression correlates with elevated MMP-3 levels and more frequent bDMARDs use. JAK inhibitors remain effective regardless of MDR1 status, potentially bypassing MDR1-mediated cellular drug resistance in RA."

Journal • Immunology • Inflammatory Arthritis • Orthopedics • Pain • Rheumatoid Arthritis • Rheumatology • ABCB1 • ICAM1 • MMP1 • MMP3

Case Reports: Peficitinib Efficacy in Treating Palmoplantar Pustulosis Induced by Paradoxical Reactions to Golimumab in Two Rheumatoid Arthritis Cases. (PubMed, Mod Rheumatol Case Rep) - "These findings suggest that peficitinib could serve as an effective alternative when tumour necrosis factor inhibitors are no longer viable. Thus, peficitinib may be a potential therapeutic option for the management of rheumatoid arthritis patients with palmoplantar pustulosis."

Journal • Dermatitis • Dermatology • Immunology • Inflammatory Arthritis • Oncology • Psoriasis • Rheumatoid Arthritis • Rheumatology

Effect of JAK Inhibitors on Osteoblast Differentiation (ACR Convergence 2025) - "This study investigates the effects of different JAK inhibitors on osteoblast differentiation using an in vitro model. To assess the impact of JAK inhibitors on osteoblast differentiation, mouse MC3T3-E1 pre-osteoblast cells were cultured in the presence of various JAK inhibitors, specifically Baricitinib (Bari), Peficitinib (Pefi), and Filgotinib (Filgo). These findings indicate that JAK inhibitors exert differential effects on osteoblast differentiation. Bari and Pefi demonstrated inhibitory activity, whereas Filgo did not affect osteoblast maturation. Furthermore, the regulation of FOXM1 expression by JAK signaling suggests a possible mechanistic link to osteoblast differentiation, warranting further investigation into its role in bone remodeling and therapeutic implications for RA treatment."

Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • FOXM1

Infection Risks Associated with Monotherapy and Combination Therapies Using Biological or Targeted - DMARD in RA: A Systematic Review and Network Meta-analysis (ACR Convergence 2025) - "By contrast, combining csDMARDs with adalimumab, infliximab, tofacitinib, or upadacitinib (though not with other b/tsDMARDs) significantly increased the risk of serious infections (OR 1.51, 95% CI: 1.04-2.19; OR 1.75, 95% CI: 1.09-2.81; OR 2.52, 95% CI: 1.26-5.03; OR 2.31, 95% CI: 1.13-4.73, respectively). For any infection, b/tsDMARD monotherapy posed a similar risk to csDMARDs, except for etanercept. Regarding specific risks, tsDMARDs were associated with an increased incidence of herpes zoster compared to csDMARDs, except for filgotinib and peficitinib. Compared to csDMARDs, b/tsDMARD monotherapy showed no elevated serious infection risk, whereas specific combination therapy regimens with csDMARDs increased the risk of serious infections in RA patients. A specialized clinical pathway with detailed recommendations was developed to assess infection risks and optimize drug selection for RA patients undergoing b/tsDMARD treatment."

Combination therapy • Monotherapy • Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Septic Shock • Tuberculosis • Varicella Zoster

Japan Post-Marketing Surveillance for Peficitinib to Assess Safety and Effectiveness in the Patients With Rheumatoid Arthritis (clinicaltrials.gov) - P=N/A | N=3000 | Recruiting | Sponsor: Astellas Pharma Inc | Trial completion date: Dec 2025 ➔ May 2026 | Trial primary completion date: Dec 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Comparative Effectiveness and Safety of Peficitinib and Abatacept for Rheumatoid Arthritis: A Multicenter, Inverse Probability Weighting Analysis. (PubMed, Mod Rheumatol) - "PEF treatment resulted in lower retention rates compared with ABT, whereas both medications demonstrated effectiveness in controlling disease activity for patients who were able to continue treatment. Our findings contribute to informed decision-making in RA treatment in actual clinical practice."

HEOR • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Determination of 13 janus kinase inhibitors in anti-alopecia cosmetics by ultra-high performance liquid chromatography-tandem triple quadrupole composite linear ion trap mass spectrometry (PubMed, Se Pu) - "Anti-alopecia cosmetics are often found to contain illegal additions of prohibited drugs such as minoxidil， finasteride and other substances...An ultra-high performance liquid chromatography-multiple reaction monitoring-information dependent acquisition-enhanced production scanning （UHPLC-MRM-IDA-EPI） method was developed to determine 13 JAK inhibitors in anti-alopecia cosmetics， including baricitinib， tofacitinib， ritlecitinib， peficitinib， abrocitinib， upadacitinib， ivarmacitinib， fedratinib， filgotinib， ruxolitinib， momelotinib， pacritinib and bozitinib...Recoveries of the 13 JAK inhibitors ranged from 94.7% to 102.2% for the water-soluble matrix and from 92.4% to 99.2% for the cream matrix， with relative standard deviations （RSDs） ≤8.8%. This method is characterized by high efficiency， rapidity， accuracy， sensitivity and simplicity， making it a powerful tool for rapid risk screening and simultaneous quantitative analysis of JAK inhibitors in anti-alopecia cosmetics."

Journal • Alopecia • Immunology

Lipid derivatized JAK-inhibitor and corticosteroid modulates saRNA-LNP inflammation while preserving protein expression (ACS-Fall 2025) - "To address this challenge, we investigated lipid-derivatized prodrugs of dexamethasone (a corticosteroid) and peficitinib (a pan-JAK inhibitor) for their ability to modulate saRNA-induced inflammation. In contrast, independent formulation strategies effectively mitigated inflammation without negatively affecting transgene expression, particularly when administering prodrugs as pre-treatment. These results underscore the importance of optimized dosing and formulation timing, providing a refined approach to minimize reactogenicity while preserving therapeutic efficacy in saRNA-based treatments."

Immune Modulation • Immunology • Inflammation

JAK2 Inhibition Augments the Anti-Proliferation Effects by AKT and MEK Inhibition in Triple-Negative Breast Cancer Cells. (PubMed, Int J Mol Sci) - "Among the four JAK2 inhibitors evaluated (fedratinib, cerdulatinib, peficitinib, and filgotinib), fedratinib significantly inhibited the proliferation of TNBC cells with IC50 values below 2 μM...Notably, combining ceduratinib with either cobimetinib (MEK inhibitor) and ipatasertib (AKT inhibitor) or trametinib (MEK inhibitor) and alpelisib (PI3K inhibitor) mimicked the effects of fedratinib on the cell proliferation, MYC and cyclin D1 suppression, and pro-apoptotic protein induction. These finding suggest that JAK2 inhibition enhances the anticancer effects of concurrent MEK/ERK and PI3K/AKT pathway inhibition, while JAK2 inhibition alone shows minimal efficacy in TNBC cells."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CCND1

The therapeutic potential for JAK inhibitors for immune-related adverse events from checkpoint inhibitors- a review of the literature. (PubMed, Rheumatology (Oxford)) - "JAK inhibitors are emerging as a promising option for the treatment of immune checkpoint inhibitor-related toxicities. The currently published evidence, primarily from case reports and case series, suggests they have efficacy, particularly in patients who have failed to respond to other cytokine inhibition strategies."

Adverse events • Checkpoint inhibition • Journal • Cardiovascular • Immunology • Melanoma • Myositis • Oncology • Rheumatology • Solid Tumor

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

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

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