Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads... Show moreAxial spondyloarthritis (axSpA) is a chronic rheumatic disease characterised by inflammation predominantly involving the spine and the sacroiliac joints. In some patients, axial inflammation leads to irreversible structural damage that in the spine is usually quantified by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Available therapeutic options include biological disease-modifying antirheumatic drugs (bDMARDs), which have been proven effective in suppressing inflammation in several randomised controlled trials (RCT), the gold standard for evaluating causal treatment effects. RCTs are, however, unfeasible for testing structural effects in axSpA mainly due to the low sensitivity to change of the mSASSS. The available literature therefore mainly includes observational research, which poses serious challenges to the determination of causality. Here, we review the studies testing the effect of bDMARDs on spinal radiographic progression, making use of the principles of causal inference. By exploring the assumptions of causality under counterfactual reasoning (exchangeability, positivity and consistency), we distinguish between studies that likely have reported confounded treatment effects and studies that, on the basis of their design, have more likely reported causal treatment effects. We conclude that bDMARDs might, indirectly, interfere with spinal radiographic progression in axSpA by their effect on inflammation. Innovations in imaging are expected, so that placebo-controlled trials can in the future become a reality. In the meantime, causal inference analysis using observational data may contribute to a better understanding of whether disease modification is possible in axSpA. Show less
Objectives To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA). Methods Patients with a clinical... Show moreObjectives To investigate the occurrence of sick leave (SL) and the impact of clinical and socioeconomic factors on SL in early axial spondyloarthritis (axSpA). Methods Patients with a clinical diagnosis of axSpA from the DEvenir des Spondyloarthrites Indifferenciees Recentes (DESIR) cohort with work-related data and up to 5-year follow-up were studied. Incidence, time to first SL and potential role of baseline and time-varying clinical and socioeconomic factors (age, gender, ethnicity, education, job type, marital and parental status) were analysed. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable time-varying Cox survival model building. Results In total, 704 axSpA patients were included (mean (SD) age 33.8 (8.6); 46% men). At baseline, 80% of patients were employed; of these, 5.7% reported being on SL. The incidence of SL among those at risk during the study period (n=620, 88%) was 0.05 (95% CI 0.03 to 0.06) per 1000 days of follow-up. Mean (SD) time to first SL was 806 (595) days (range: 175-2021 days). In multivariable models, male gender (HR 0.41 (95% CI 0.20 to 0.86)) and higher education (HR 0.48 (95% CI 0.24 to 0.95)) were associated with lower hazard of SL, while higher disease activity (HR 1.49 (95% CI 1.04 to 2.13)), older age, smoking and use of tumour necrosis factor inhibitors were associated with higher hazard of SL. Conclusions In this early axSpA cohort of young, working-age individuals, male gender and higher education were independently associated with a lower hazard of SL, whereas older age and higher disease activity were associated with higher hazard of SL. The findings suggest a role of socioeconomic factors in adverse work outcomes, alongside active disease. Show less
Putrik, P.; Ramiro, S.; Lie, E.; Keszei, A.P.; Kvien, T.K.; Heijde, D. van der; ... ; Boonen, A. 2016
