Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference

Abstract

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 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.

Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis

“…While VCI is associated with syndesmophyte development, medication use is, to our current knowledge, not directly associated with the syndesmophyte development but rather through its effect of reducing inflammation. 13 Hence, adjusting for medication when studying the association between VCI and syndesmophyte development could erroneously remove part of the total effect.…”

Age-stratified trends in the progression of spinal radiographic damage in patients with ankylosing spondylitis: a longitudinal study

“…A dedicated study design that handles potential confounding by indication is required to address the causal effects of medication. 16 , 31 In this study, we set out to trace the course of radiographic progression in stratified age groups, so we acknowledge that the underrated effect of TNF inhibitors in our results is probably due to our rather simple binary measure for TNF inhibitor use. Data for the use of nonsteroidal anti-inflammatory drugs (NSAIDs) were not used because a considerable number of our patients received on-demand NSAID treatment; therefore, obtaining complete information about the dose and frequency of NSAID intake was infeasible.…”

[Retracted] Radiation Exposure of Crystalline Bodies during Interventional Therapy and Related Research Status

“…e use of various radiation protection facilities, such as the use of movable lead protective hanging curtains, lead clothes, lead bibs, and lead protective glasses, has greatly reduced the exposure dose of intervention workers to a certain extent, and ensured the health of intervention workers [12]. In the above-mentioned radiation protection measures, most of the protective facilities are in place and have achieved good protection effects [13,14]. However, the use rate of lead protective glasses is very low.…”