Is the risk of infection higher during treatment with secukinumab than with TNF inhibitors? An observational study from the Nordic countries

Objectives The positioning of secukinumab in the treatment of axial SpA (axSpA) and PsA is debated, partly due to a limited understanding of the comparative safety of the available treatments. We aimed to assess the risk of the key safety outcome infections during treatment with secukinumab and TNF inhibitors (TNFi). Methods Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IRs) with 95% CIs per 100 patient-years were calculated. Adjusted hazard ratios were estimated through Cox regression, with secukinumab as the reference. Several sensitivity analyses were performed to investigate confounding by indication. Results Among 7708 patients with SpA and 5760 patients with PsA, we identified 16 229 treatment courses of TNFi (53% bionaive) and 1948 with secukinumab (11% bionaive). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi lying in between these values. The adjusted HR for adalimumab, compared with secukinumab, was 0.58 (0.39-0.85). In sensitivity analyses, the difference from secukinumab was somewhat attenuated and in some analyses no longer statistically significant. Conclusion When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.Peer reviewe

Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naive patients with rheumatoid arthritis

Objectives To compare treatment effectiveness in rheumatoid arthritis (RA) patients naïve to biological disease-modifying antirheumatic drugs (bDMARDs) treated with tocilizumab (TCZ) or TNF-inhibitor (TNFi) with (-combo) or without (-mono) conventional synthetic DMARDs (csDMARDs). Methods Patients with RA across 7 European registries, naïve to bDMARDs who initiated treatment with TCZ or TNFi from 2009 to 2016 were included. Drug retention rate was analyzed using Kaplan–Meier and Cox models, and CDAI over time by mixed models. The proportions of patients reaching CDAI low disease activity (LDA) and remission after one year were corrected for attrition. Results 6713 TNFi-combo, 3762 TNFi-mono, 646 TCZ-combo and 384 TCZ-mono were eligible. Crude median retention was 3.67 years (95%CI 3.41-3.83) for TNFi-combo, 4.14 (3.77-4.62) for TNFi-mono, 2.98 (2.76-3.34) for TCZ-combo and 3.63 years (3.34-5.03) for TCZ-mono. After adjustment for covariates, country and year of treatment initiation stratification, hazards of discontinuation were lower for TCZ-mono (0.60, 95% CI 0.52-0.69) and TCZ-combo (0.66, 95% CI 0.54-0.81) compared to TNFi-combo. Adjusted CDAI evolution was not significantly different between groups. CDAI LDA and remission corrected for attrition were similar between TCZ with or without csDMARDs and TNFi-combo. Conclusion In routine care across 7 European countries, the adjusted drug retention, adjusted CDAI over time and attrition-corrected response proportion for RA patients were similar for bio-naïve patients if treated with TNFi-combo, TCZ-combo or TCZ-mono.Peer reviewe

Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study) : Protocol for a Randomized, Controlled Open-Label Noninferiority Trial

Funding Information: The ReMonit study and the qualitative substudy received funding from the South-Eastern Norway Regional Health Authority (funding number 2021062) and the Centre for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway (funding number 328657).Peer reviewe

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers : the Nordic example

RMD Open 2018;4:e000655. doi:10.1136/ rmdopen-2018-000655Peer reviewe

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE

Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries

Objective There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. Methods Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. Results A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (4 years), and varied significantly across the European registries. Conclusion In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.Peer reviewe

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration

Background JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. Methods In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. Results We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. Conclusion The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.Peer reviewe

Commonalities and differences in set-up and data collection across European spondyloarthritis registries : results from the EuroSpA collaboration

Funding Open access funding provided by Royal Library, Copenhagen University Library The EuroSpA Research Collaboration Network was financially supported by Novartis Pharma AG. Novartis had no influence on the data collection, statistical analyses, manuscript preparation or decision to submit the manuscript.Peer reviewedPublisher PD

Predictors of ASDAS-CRP inactive disease in axial spondyloarthritis during treatment with TNF-inhibitors : Data from the EuroSpA collaboration

Correction: Volume 58, Article Number 152141 DOI: 10.1016/j.semarthrit.2022.152141 Published: FEB 2023Objectives: In patients with axial spondyloarthritis (axSpA) initiating their first tumor necrosis factor alpha-inhibitor (TNFi), we aimed to identify common baseline predictors of Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) inactive disease (primary objective) and clinically important improvement (CII) at 6 months, and drug retention at 12-months across 15 European registries. Methods: Baseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data. Results: The consistency of baseline predictors in individual registries justified pooling the data. In the pooled dataset (n = 21,196), the 6-month rates for ASDAS inactive disease and ASDAS CII were 26% and 51%, and the 12-month drug retention rate 65% in patients with available data (n = 9,845, n = 6,948 and n = 21,196, respectively). Nine common baseline predictors of ASDAS inactive disease, ASDAS CII and 12-month drug retention were identified, and the odds ratios (95%-confidence interval) for ASDAS inactive disease were: age, per year: 0.97 (0.97-0.98), men vs. women: 1.88 (1.60-2.22), current vs. non-smoking: 0.76 (0.63-0.91), HLA-B27 positive vs. negative: 1.51 (1.20-1.91), TNF start year 2015-2018 vs. 2009-2014: 1.24 (1.06-1.45), CRP > 10 vs.Peer reviewe