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 ... -  《-》

Venous thromboembolism with JAK inhibitors and other immune-modulatory drugs: a Swedish comparative safety study among patients with rheumatoid arthritis.

To assess and compare the incidence of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi) or other biological disease modifying antirheumatic drugs (bDMARDs). For contextualisation, to assess VTE incidences in the Swedish general population and in the RA source population. We performed a nationwide register-based, active comparator, new user design cohort study in Sweden from 2010 to 2021. The Swedish Rheumatology Quality Register was linked to national health registers to identify treatment cohorts (exposure) of initiators of a JAKi, a TNFi, or a non-TNFi bDMARD (n=32 737 treatment initiations). We also identified a general population cohort (matched 1:5, n=92 108), and an 'overall RA' comparator cohort (n=85 722). Outcome was time to first VTE during the follow-up, overall and by deep vein thrombosis (DVT) and pulmonary embolism (PE). We calculated incidence rates (IR) and multivariable-adjusted HRs using Cox regression. Based on 559 incident VTE events, the age- and sex-standardised (to TNFi) IR (95% CI) for VTE was 5.15 per 1000 person-years (4.58 to 5.78) for patients treated with TNFi, 11.33 (8.54 to 15.04) for patients treated with JAKi, 5.86 (5.69 to 6.04) in the overall RA cohort and 3.28 (3.14 to 3.43) in the general population. The fully adjusted HR (95% CI) for VTE with JAKi versus TNFi was 1.73 (1.24 to 2.42), the corresponding HR for PE was 3.21 (2.11 to 4.88) and 0.83 (0.47 to 1.45) for DVT. Patients with RA treated with JAKi in clinical practice are at increased risk of VTE compared with those treated with bDMARDs, an increase numerically confined to PE.

Molander V ，Bower H ，Frisell T ，Delcoigne B ，Di Giuseppe D ，Askling J ，ARTIS study group ... -  《-》

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 ... -  《-》

Cardiovascular safety of the class of JAK inhibitors or tocilizumab compared with TNF inhibitors in patients with rheumatoid arthritis: Systematic review and a traditional and Bayesian network meta-analysis of randomized clinical trials.

We aimed to compare the risk of major adverse cardiovascular events (MACE) and all-cause of death (ACD) in patients with rheumatoid arthritis (RA) treated with JAK inhibitors (JAKi) or tocilizumab (TCZ) versus tumor necrosis factor (TNF) inhibitors (TNFi). We performed a systematic review of six medical databases until May, 2024 for phase 2-4 randomized controlled trials (RCTs) evaluating patients with RA treated with TCZ or JAKi (intervention arm) compared with controls (TNFi or placebo). The study data were independently assessed by 3 investigators. The risk of bias was assessed using the Cochrane Collaboration tool. We performed a network meta-analysis with random effects to evaluate the risk of MACE (primary outcome) and ACD (secondary outcome) compared to TNFi. We also calculated the posterior probability of increasing the primary and secondary outcomes by 15% or more (PP15%) following Bayes' theorem. This meta-analysis included 18 RCTs with 21,432 patients and 57,040 patient-years. JAKi were linked to a non-statistically significant increase in the risk of MACE and ACD as compared to TNFi (ORs of 1.232 [95%CI 0.86-1.76]; p = 0.56 and ORs = 1.3903[95%CI 0.94-2.07]; p = 0.10, respectively). By Bayesian analysis, a high clinical probability of more frequent MACE (PP15% of 61%) and ACD (PP15% of 84%) was found in the JAKi group than in the TNFi group. No statistical difference was found between TCZ and TNFi in relation to MACE (1.029 [95%CI 0.75 -1.40]; p = 0.86) and ACD (1.072 [95%CI 0.78-1.48]; p = 0.67]) in the traditional meta-analysis. In the Bayesian approach, the probability of a difference in clinical relevance was low (PP15% for MACE of 11% and PP15% for ACD of 25%). The main limitation of this study is the small number of events with JAKi other than tofacitinib, reflecting the importance of ORAL SURVEILLANCE. Despite this, these data reinforce the recommendations of regulatory agencies and rheumatology societies on the use of JAKi in the context of RA, but above all call for more direct comparison studies involving primary safety outcomes with JAKi, since the outcome data available are still small and heterogeneous. In both meta-analyses, no difference was found between TNFi and TCZ.

Pugliesi A ，Oliveira DGC ，Filho VAS ，Machado JO ，Pereira AG ，Bichuette JCS ，Sachetto Z ，de Carvalho LSF ，Bertolo MB ... -  《-》

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 ... -  《-》