Objective. To investigate the effect of therapies on radiographic progression in patients with axial spondyloarthritis (SpA). Methods. A comprehensive database search for studies assessing radiographic progression in axial SpA (particular treatment versus no treatment of interest) was performed. Study-specific standardized mean differences in treatment outcomes at 2 and ≥4 years were estimated and combined using random-effects models.Results. Twenty-four studies in patients with axial SpA were identified, of which 18 involved tumor necrosis factor inhibitors (TNFi), 8 involved nonsteroidal antiinflammatory drugs (NSAIDs), and 1 involved secukinumab. Spinal radiographic progression, as measured by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), was not significantly different between TNFi-treated and biologics-naive patients at 2 years (mSASSS difference −0.73 [95% confidence interval (95% CI) −1.52, 0.12], I 2 = 28%) and ≥4 years (mSASSS difference −2.03 [95% CI −4.63, 0.72], I 2 = 63%). Sensitivity analyses restricted to studies with a low risk of bias showed a significant difference in spinal radiographic progression between TNFi-treated and biologics-naive patients at ≥4 years (mSASSS difference −2.17 [95% CI −4.19, −0.15]). No significant difference in spinal radiographic progression was observed between NSAID-treated and control patients (mSASSS difference −0.30 [95% CI −2.62, 1.31], I 2 = 71%) or between secukinumab-treated and biologics-naive patients (mSASSS difference −0.34 [95% CI −0.85, 0.17]). With regard to treatment differences in patients with nonradiographic axial SpA or in patients with radiographic progression measured using the sacroiliac joint score, an insufficient number of studies were available for analysis.Conclusion. Although no significant protective effect of TNFi treatment on spinal radiographic progression was seen over the course of 2 years or ≥4 years in patients with axial SpA, our analysis restricted to studies with a low risk of bias showed a protective effect of TNFi after ≥4 years. Therefore, long-term TNFi exposure might confer beneficial effects on spinal radiographic progression in axial SpA. No difference in radiographic progression at 2 years was seen in either the NSAID or secukinumab treatment groups compared to their controls. Future studies should explore the effects of biologic treatment on radiographic progression, as well as the effects of long-term biologics exposure, in patients with early axial SpA or those with nonradiographic axial SpA.

Introduction Non-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS. Methods A comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model. Results Nine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I 2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I 2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I 2 = 76%). Conclusions In this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00248-x) contains supplementary material, which is available to authorized users.

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