Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

Hernández-Cruz B ，Otero-Varela L ，Freire-González M ，Busquets-Pérez N ，García González AJ ，Moreno-Ramos M ，Blanco-Madrigal JM ，Manrique-Arija S ，Perez-Pampin E ，Ruiz-Montesino D ，Sánchez-Alonso F ，Sanchez-Piedra C ，Castrejón I ，BIOBADASER Study Group ... -  《-》

Real-World Persistence and Effectiveness of Upadacitinib versus Other Janus Kinase Inhibitors and Tumor Necrosis Factor Inhibitors in Australian Patients with Rheumatoid Arthritis.

Youssef P ，Ciciriello S ，Tahir T ，Leadbetter J ，Butcher B ，Calao M ，Walsh N ，O'Sullivan C ，Smith T ，Littlejohn G ... -  《-》

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

Aymon R ，Mongin D ，Bergstra SA ，Choquette D ，Codreanu C ，De Cock D ，Dreyer L ，Elkayam O ，Huschek D ，Hyrich KL ，Iannone F ，Inanc N ，Kearsley-Fleet L ，Koca SS ，Kvien TK ，Leeb BF ，Lukina G ，Nordström DC ，Pavelka K ，Pombo-Suarez M ，Rodrigues A ，Rotar Z ，Strangfeld A ，Verschueren P ，Westermann R ，Zavada J ，Courvoisier DS ，Finckh A ，Lauper K ... -  《-》

Comparison of retention of biologics in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.

This multicentre, retrospective study aimed to compare retention and reasons for discontinuation between Janus kinase inhibitors (JAKi) and biologic DMARDs in patients with elderly-onset rheumatoid arthritis (EORA). Patients with RA enrolled in a Japanese multicentre observational registry between 2015 and 2022 were included. EORA was defined as RA with onset at age 60 or over. To adjust confounding factors by indication for initiation of TNF inhibitors (TNFi), IL-6 inhibitors (IL-6i), cytotoxic T-lymphocyte associated antigen 4 immunoglobulin (CTLA4-Ig) blockers, or JAKi, a propensity score based on baseline characteristics was used to compare drug retention. To assess the reasons for discontinuation, retention rates for ineffectiveness, adverse events and remission were analysed as secondary outcomes. A total of 572 patients with 835 treatment courses were identified (314 TNFi, 175 IL-6i, 228 CTLA4-Ig and 118 JAKi). After adjusting for differences in baseline characteristics, drug retention was significantly higher for IL-6i (hazard ratio [HR] = 0.38; 95% CI: 0.27, 0.55; P < 0.01) as compared with TNFi. Discontinuation due to lack of effectiveness was lower with JAKi (HR = 0.38; 95% CI: 0.22, 0.66; P < 0.01) and IL-6i (HR = 0.29; 95% CI: 0.19, 0.46; P < 0.01) as compared with TNFi although CTLA4-Ig had a similar HR to TNFi. The adjusted incidence of discontinuation due to adverse events was higher for JAKi (HR = 2.86; 95% CI: 1.46, 5.59; P < 0.01) than for TNFi. In EORA patients, IL-6i and JAKi had longer retention and less discontinuation due to ineffectiveness than TNFi. The potential risks of JAKi should be approached with an individualized perspective.

Jinno S ，Onishi A ，Hattori S ，Dubreuil M ，Ueda Y ，Nishimura K ，Okano T ，Yamada H ，Yamamoto W ，Murata K ，Onizawa H ，Ebina K ，Maeda Y ，Son Y ，Amuro H ，Hara R ，Hata K ，Shiba H ，Katayama M ，Watanabe R ，Hashimoto M ，Saegusa J ... -  《-》

Cancer risks with JAKi and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis or psoriatic arthritis: a national real-world cohort study.

Assess cancer risks with Janus kinase inhibitors (JAKi) versus biological disease-modifying antirheumatic drugs (bDMARDs) in clinical practice. Cohort study of patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) initiating treatment with JAKi, tumour necrosis factor inhibitors (TNFi) or other (non-TNFi) bDMARDs 2016-2020 using prospectively collected data from the Swedish Rheumatology Quality Register linked to other registers including the Cancer Register. We estimated incidence rates, and HRs via Cox regression, for all cancers excluding non-melanoma skin cancer (NMSC), and for individual cancer types including NMSC. We identified 10 447 patients with RA and 4443 patients with PsA who initiated treatment with JAKi, a non-TNFi bDMARD or a TNFi. Median follow-up times in RA were 1.95, 2.83 and 2.49 years, respectively. In RA, based on 38 incident cancers other than NMSC with JAKi vs 213 with TNFi the overall HR was 0.94 (95% CI 0.65 to 1.38). Based on 59 vs 189 incident NMSC, the HR was 1.39 (95% CI 1.01 to 1.91). At 2 or more years since treatment start, the HR for NMSC was 2.12 (95% CI 1.15 to 3.89). In PsA, based on 5 vs 73 incident cancers other than NMSC, and 8 vs 73 incident NMSC, the corresponding HRs were 1.9 (95% CI 0.7 to 5.2) and 2.1 (95% CI 0.8 to 5.3). In clinical practice, the short-term risk of cancer other than NMSC in individuals initiating treatment with JAKi is not higher than for TNFi, but we found evidence of increased risk for NMSC.

Huss V ，Bower H ，Hellgren K ，Frisell T ，Askling J ，Behalf of the ARTIS group ，behalf of the ARTIS group ... -  《-》