according to an analysis of studies with low risk of bias, but no evidence exists for slowed disease progression at the sacroiliac joint, according to a systematic review and meta-analysis of 24 studies.
The review, conducted by Paras Karmacharya, MBBS, and colleagues at the Mayo Clinic in Rochester, Minn., did not find a significant protective effect overall for tumor necrosis factor inhibitor (TNFi) treatment on radiographic progression of ankylosing spondylitis at the spine at 2 and 4 years. But when the researchers restricted the analysis to six studies of TNFi with low risk of bias, the results were significant for slowing radiographic progression at 4 years or more (modified Stoke Ankylosing Spondylitis Spine Score [mSASSS] difference, –2.17).
NSAIDs did not show any benefit in slowing progression at either the spine or sacroiliac joint over a shorter 2-year time span for which results were available. The single study of secukinumab (Cosentyx) that was included in the analysis did not show a significant difference in radiographic progression over 2 years (mean mSASSS difference, –0.34).
For the few studies that included data on radiographic progression in patients with nonradiographic axial spondyloarthritis, there was no effect seen on the spine with either high or low NSAID use at 2 years and no evidence for an effect of TNFi on progression at the sacroiliac joint.
“Although our study showed a significant effect of TNFi on long-term radiographic progression (in sensitivity analysis), none of the included studies provide prospective, long-term, controlled comparison. Most included studies were judged to have a low risk of bias; however predominance of observational and open-label extensions of randomized, controlled trials limits overall level of evidence,” the authors wrote in Arthritis & Rheumatology.
Any benefits of early treatment on slowing the natural progression of disease might support introducing the treatment early with a treat-to-target strategy, similar to RA, the researchers noted. However, “the current guidelines recommend against this due to lack of evidence.”
The analysis involved 18 studies with TNFi, 8 with NSAIDs, and 1 with secukinumab (3 studies contained data for both NSAIDs and TNFi). The investigators used a change of 2 mSASSS units in 2 years or one new syndesmophyte formation in 2 years as the primary endpoint for radiographic progression.
“Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axial spondyloarthritis; their use in the group with high risk of progression should be evaluated with a follow-up [longer than] 4 years to see if effects are more pronounced over time. Newer measures with higher sensitivity to detect structural changes, such as those based on quantitative low-dose CT should be compared to mSASSS for use in clinical trials,” the researchers concluded.
The work was funded by various grants from the National Institutes of Health. The authors reported no relevant disclosures.
SOURCE: Karmacharya P et al. Arthritis Rheumatol. 2020 Jan 20. doi: 10.1002/art.41206.