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

Are They Interchangeable?

Funding Information: On behalf of the EuroSpA Scientific Committee, the authors acknowledge Novartis Pharma AG and IQVIA for supporting the EuroSpA Research Collaboration Network. Publisher Copyright: © 2024 The Journal of Rheumatology.Objective. Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs. Methods. We used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other. Results. In 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data. Conclusion. We estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.publishersversionpublishe

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

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF-inhibitor : results from 13 European registries

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 reviewe

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF-inhibitor: results from 13 European registries.

OBJECTIVES In bio-naïve patients with Psoriatic arthritis (PsA) initiating a Tumour Necrosis Factor inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. METHODS Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes, were defined as common predictors. RESULTS In the pooled cohort (n = 13 369), six-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6,954, n = 5,275 and n = 13 369, respectively). Baseline predictors of remission, moderate response and 12-month drug retention were identified, five common across all three outcomes. Odds ratios (95% confidence interval) for DAPSA28 remission were: age, per year: 0.97 (0.96-0.98); disease duration, years (10 vs ≤ 10 mg/l: 1.52 (1.22-1.89) and one mm increase in patient fatigue score: 0.99 (0.98-0.99). CONCLUSION Baseline predictors of remission, response and adherence to TNFi were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalisable from the country- to disease-level

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

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

ObjectivesIn 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.MethodsBaseline demographic and clinical characteristics were collected. Outcomes were investigated per registry and in pooled data using logistic regression analyses on multiply imputed data.ResultsThe 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. ≤10 mg/l: 1.49 (1.25–1.77), one unit increase in health assessment questionnaire (HAQ): 0.77 (0.58–1.03), one-millimeter (mm) increase in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) fatigue and spinal pain: 0.99 (0.99–1.00) and 0.99 (0.99–1.99), respectivelyConclusionCommon baseline predictors of treatment response and adherence to TNFi could be identified across data from 15 European registries, indicating that they may be universal across different axSpA populations.</p