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

Emerging and Investigational JAK Inhibitors for Rheumatoid Arthritis: Efficacy and Safety. (PubMed, Drug Des Devel Ther) - "Peficitinib has the most mature evidence base, including Phase 3 efficacy, radiographic protection, long-term extension data, and pooled safety analyses. Ivarmacitinib has phase 3 and exploratory MRI data, whereas the phase 3 trial of TLL-018 has reached primary completion, with sponsor-reported topline findings available but complete results not yet published. CPL409116/CPL'116 remains supported by limited Phase 2 evidence. Decernotinib represents an informative historical proof-of-concept programme. Overall, no emerging agent has yet demonstrated a reproducible advantage over established JAK inhibitors in sustained remission, structural preservation, difficult-to-treat disease, or overall benefit-risk balance. Future development should prioritise active comparators, prespecified structural outcomes, prolonged safety assessment, and prospectively validated treatment-specific biomarkers."

Journal • Review • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Dosing Time-Dependent Anti-arthritic Effects of Peficitinib in Collagen-Induced Arthritis Rats. (PubMed, Biol Pharm Bull) - "We previously reported that stronger therapeutic effects were observed in rheumatoid arthritis (RA) patients and RA model animals when the dosing times of methotrexate (MTX) and tacrolimus were selected according to the circadian rhythms of the inflammatory response and cytokine levels. Plasma levels were higher in the 5:00-treated group than in the 17:00-treated group, and the area under the curve0→12h was 1.24-fold higher in the 5:00-treated group. These results suggest that improvements in the therapeutic index of RA therapy are achievable by administering peficitinib at a time of day when the inflammatory reaction begins to activate, cytokine levels start to increase, and blood concentrations become higher."

Journal • Preclinical • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Real-World Drug Retention and Determinants of Discontinuation of JAK Inhibitors and Biological DMARDs in Rheumatoid Arthritis: A Cohort Study of 1,725 Treatment Episodes (EULAR 2026) - "bDMARDs were categorized as TNFi (N=733), IL-6R inhibitors (tocilizumab/sarilumab; N=310), and CTLA4-Ig (abanacept; N=132)...Factors associated with discontinuation (full cohort, n=1,725; discontinuations=1,179): Compared with baricitinib (reference): Filgotinib: HR 0.80, 95% CI 0.56–1.15 Upadacitinib: HR 0.65, 95% CI 0.35–1.34 Tofacitinib: HR 1.33, 95% CI 0.91–1.93 Peficitinib: HR 2.14, 95% CI 1.17–3.79, p = 0.012 TNFi: HR 1.49, 95% CI 1.17–1.91, p = 0.001 IL-6R inhibitors: HR 2.07, 95% CI 1.61–2.67, p < 0.001 CTLA4-Ig: HR 2.15, 95% CI 1.26–2.87, p < 0.001 Additional significant predictors: GC co-administration: HR 1.21, 95% CI 1.07–1.36, p = 0.001 Treatment line effect: 2nd line: HR 1.35, 95% CI 1.14–1.61 3rd line: HR 1.66, 95% CI 1.26–2.19 ≥4th line: HR 1.98, 95% CI 1.44–2.71, p < 0.001 Prior IL-6R inhibitor exposure showed a trend toward higher discontinuation (HR 1.80,p=0.067)...Treatment discontinuation was strongly influenced by treatment line, GC..."

Clinical • Real-world • Real-world evidence • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • MMP3

Infection risks associated with b/tsDMARDs in rheumatoid arthritis: a systematic review and network meta-analysis. (PubMed, Eur J Clin Pharmacol) - "Compared to csDMARDs, b/tsDMARD monotherapy showed no elevated serious infection risk, whereas specific combinations increased the risk of serious infections in RA patients. A clinical reference pathway was developed to inform drug selection optimization for RA patients receiving b/tsDMARDs."

Journal • Retrospective data • Review • Gastroenterology • Gastrointestinal Disorder • Herpes Zoster • Immunology • Infectious Disease • Inflammatory Arthritis • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Varicella Zoster

Real-world comparison of herpes zoster risk among five Janus kinase inhibitors in rheumatoid arthritis: the ANSWER cohort study. (PubMed, Joint Bone Spine) - "Filgotinib showed a lower observed risk of HZ compared with tofacitinib, baricitinib, and upadacitinib. Given the limited number of events and observational design, further large-scale studies with longer follow-up are warranted to confirm these findings."

Journal • Real-world evidence • Herpes Zoster • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • Varicella Zoster

Large-scale meta-analysis of infection risk with JAK-STAT inhibitors in 29,000 patients. (PubMed, J Eur Acad Dermatol Venereol) - "This meta-analysis provides a comprehensive assessment of the risk of infection associated with JAK-STAT inhibitors in IMIDs of the skin. Although overall safety is acceptable, clinicians should be aware of the higher infection risk of influenza and herpes zoster and should consider vaccination and preventive strategies for high-risk patients with atopic dermatitis. The main limitation is that the included studies involved highly selected populations with few comorbidities and short follow-up."

Journal • Retrospective data • Review • Alopecia • Atopic Dermatitis • Dermatitis • Dermatology • Herpes Zoster • Immunology • Infectious Disease • Inflammation • Influenza • Pulmonary Disease • Respiratory Diseases • Varicella Zoster • Vitiligo

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

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

Differential JAK Family Inhibition and Clinical Outcomes in Rheumatoid Arthritis: The Role of JAK3 Selectivity With Peficitinib. (PubMed, Int J Rheum Dis) - No abstract available

Clinical data • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • JAK3

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis. (PubMed, Ann Rheum Dis) - "This SLR, together with the safety review, informed the 2025 update of the EULAR RA management recommendations. Although few phase 3 trials on novel agents were available, strategic and head-to-head studies provided important insights that enabled further refinement of the established treatment algorithm."

Journal • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Comparative Effectiveness of Upadacitinib vs. Other JAK Inhibitors in Patients With Rheumatoid Arthritis in a Global Real-World Setting. (PubMed, Rheumatol Ther) - "This real-world study of patients with RA showed that greater proportions of patients who received upadacitinib attained physician-reported DAS28 remission, absence of pain, and complete adherence to medication compared with patients receiving other JAKis."

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

Formulation and administration timing of lipid derivatized JAK-inhibitor and corticosteroid modulate saRNA-LNP inflammation and expression. (PubMed, J Control Release) - "To address this challenge, we investigated lipid-derivatized prodrugs of peficitinib (a pan-JAK inhibitor) and dexamethasone (a corticosteroid) for their ability to modulate saRNA-LNP induced inflammation. By contrast, independent delivery delayed these responses by a few hours, preserving saRNA replication and expression while still mitigating inflammation. Collectively, these results emphasise that the formulation strategy, and timing - not drug identity alone, influence the trade-off between controlling reactogenicity and maintaining transgene expression, offering a refined pathway toward reducing reactogenicity while maximizing the therapeutic potential of saRNA-LNP therapeutics."

Journal • Immunology • Inflammation

Janus Kinase (JAK) Inhibitors in Rheumatoid Arthritis. (PubMed, Cureus) - "Only studies involving adult patients with RA treated by approved JAKis (baricitinib, tofacitinib, upadacitinib, peficitinib, and filgotinib) were included...JAKis consistently demonstrated superior responses compared with placebo and methotrexate, with higher American College of Rheumatology 20% response rates, improved disease activity scores, reduced radiographic progression, and enhanced patient-reported outcomes. In head-to-head comparisons, baricitinib and upadacitinib demonstrated advantages over adalimumab across multiple efficacy domains...Nonetheless, their use requires individualized, risk-stratified decision-making, with particular caution in patients at elevated cardiovascular or malignancy risk. Ongoing long-term studies and real-world data remain essential to further define their benefit-risk profile and optimize their integration into personalized RA care."

Journal • Review • Cardiovascular • Herpes Zoster • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • Varicella Zoster

Safety and efficacy of different JAK inhibitors in the treatment of inflammatory bowel disease: a network meta-analysis. (PubMed, Front Pharmacol) - "This network meta-analysis aimed to compare the efficacy and safety of various JAK inhibitors, including brepocitinib, filgotinib, ivarmacitinib, peficitinib, ritlecitinib, tofacitinib, and upadacitinib, in patients with IBD. Long-term studies are needed to confirm these results. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024595343, Identifier CRD42024595343."

Journal • Retrospective data • Review • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

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