TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort

Abstract

ObjectivesTo analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS).MethodsPatients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis.ResultsA total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97).ConclusionTNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

Cytokine-Induced and Stretch-Induced Sphingosine 1-Phosphate Production by Enthesis Cells Could Favor Abnormal Ossification in Spondyloarthritis

“…Anti‐TNF‐α and, more recently, anti‐IL‐17 antibodies are currently being used as a treatment to relieve pain for SpA patients in addition to nonsteroidal anti‐inflammatory drugs . Long‐term follow‐up studies have revealed that these biotherapies also slow radiographic progression of spinal fusion . In interaction with inflammation, mechanical stress is also assumed to participate in SpA pathogenesis .…”

Targeting tumor necrosis factor receptors in ankylosing spondylitis

“…Extensions of pivotal randomized clinical trials (RCTs) failed to show an inhibitory effect of adalimumab, infliximab, and entanercept on spinal structural changes over a period of 2 years . However, accumulating evidence from retrospective analyses of well‐characterized cohorts shows that TNF inhibitors are associated with a reduction in spinal radiographic progression, an effect attributed to their ability to suppress disease activity . The need for an extended prospective RCT against placebo that could prove causality cannot be overstated; however, such studies would be impossible to conduct due to ethical considerations.…”

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

“…Currently there are five anti‐TNF agents available for clinical use in ankylosing spondylitis: adalimumab (ADA) and golimumab (both fully human monoclonal antibodies), infliximab (IFX; chimeric monoclonal antibody with a murine variable region), certolizumab (humanized Fab fragment conjugated to polyethylene glycol), and etanercept (ETN; fusion protein of 2 TNFR2 receptor extracellular domains and the Fc fragment of human immunoglobulin 1). TNF inhibitors proved to be effective in patients with ankylosing spondylitis in improving clinical symptoms, and in long‐term use they may prevent structural damage progression . TNF inhibitors are indicated in patients with ankylosing spondylitis with failure of standard treatment and high disease activity (Ankylosing Spondylitis Disease Activity Score ≥2.1 or Bath Ankylosing Spondylitis Disease Activity Index ≥4) .…”