Long-Term TNFi Exposure May Provide Radiographic Progression Benefit in Axial Spondyloarthritis

MRI scan of human lumbar spine with doctor
Researchers investigated the effect of different therapies on radiographic progression in axial spondyloarthritis.

Long-term exposure to tumor necrosis factor inhibitor (TNFi) therapies may benefit radiographic progression in axial spondyloarthritis (axSpA), according to research results published in Arthritis & Rheumatology.

Researchers conducted a systematic review and meta-analysis examining the effect of different treatment options on radiographic progression in axSpA. Data from cohort and case-control studies published through January 16, 2019 were included; cross-sectional studies, case series, case reports, and non-human studies were excluded from the study. The primary outcome measure was the between-group difference in modified Stroke AS Spine Score (mSASSS) in ankylosing spondylitis (AS) at 2 years and ≥4 years. Other radiographic scores were secondary outcomes.

A total of 524 studies were screened, of which 24 met the following inclusion criteria: evaluation of efficacy of a therapeutic intervention, compared with placebo or other controls, in adults with axSpA (including AS and nonradiographic-axSpA [nr-axSpA]) who were followed up for at least 1 year. Therapy efficacy was determined by quantitatively scoring radiographic progression of disease. The studies examined 3 available pharmacologic treatments, including TNFis (18 studies, n=4874), nonsteroidal anti-inflammatory drugs (NSAIDs; 8 studies, n=2321), and secukinumab (1 study, n=237). Three of the 24 studies reported data for both NSAIDs and TNFis. The included studies were primarily cohort studies and open label extensions of randomized controlled trials.

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Of the TNFi studies, 17 addressed AS and 1 addressed nr-axSpA. In addition, 6 studies used a historical cohort for comparison and 2 used contemporary cohorts. Among these studies, the type of TNFi utilized was variable and included infliximab, etanercept, adalimumab, and golimumab, both alone and in combination.

Of the 8 NSAID studies, 6 focused only on AS, 1 on early axSpA, and 1 on both AS and nr-axSpA. Six studies reported mSASSS, 1 reported the Bath AS Radiology Index (BASRI) spine score, and 1 reported the BASRI-sacroiliac joint score.

For the assessment of spinal radiographic progression with TNFi among patients with AS, most studies reported mSASSS; 1 study reported a computed tomography score of facet joints. No studies assessed spinal radiographic progression in nr-axSpA. Investigators found that spinal radiographic progression was not significantly different among biologic-naive and TNFi-treated patients at 2 years (mSASSS difference, -0.73; 95% CI, -1.52 to 0.12; I²=28%) and at ≥4 years (mSASSS difference, -2.03; 95% CI, -4.63 to 0.72; I²=63%). However, a sensitivity analysis of 6 studies with low risk for bias found a significant difference at ≥4 years (mSASSS difference, -2.17; 95% CI, -4.19 to -0.15; I²=49%).

The 6 studies that reported 2-year follow-up of mSASSS with NSAID use in AS found no significant difference between the NSAID and control groups (standardized mean difference, -0.08; 95% CI, -0.32 to 0.16; mSASSS difference, -0.30; 95% CI, -2.62 to 1.31; I²=71%). In a subgroup analysis (continuous vs on-demand NSAID use), there were no differences (P =.79) in the NSAID index high vs low and in the NSAIDs vs no NSAIDs studies. In 1 study comparing BASRI-spine for NSAID with control participants, no difference was noted (BASRI-spine difference, 0.020; 95% CI, -0.44 to 0.48). No mSASSS difference was observed in a study that reported on a subgroup of patients with nr-axSpA (mSASSS difference, 0.13; 95% CI, -0.39 to 0.65).

Results of the 1 study that assessed secukinumab did not indicate any significant difference in radiographic progression over 2 years (mean mSASSS difference, -0.34; 95% CI, -0.85 to 0.17).

“Long-term TNFi exposure might have radiographic progression benefit. No difference was seen with NSAIDs or secukinumab…at 2 years but long-term data were not available,” the researchers concluded. “Further studies should explore the effect of NSAIDs and biologics alone and in combination in patients with early axSpA.”


Karmacharya P, Duarte-Garcia A, Dubreuil M, et al. The effect of therapy on radiographic progression in axial spondyloarthritis: A systematic review and meta-analysis [published online January 20, 2020]. Arthritis Rheumatol. doi:10.1002/art41206