According to study data results published in PLOS One, tumor necrosis factor (TNF) inhibition, and not methotrexate (MTX) monotherapy, effectively reduced complement activation in spondyloarthropathies (SpA).1

Investigators conducted an observational prospective study of patients with SpA initiating methotrexate (MTX) monotherapy (n=16), anti-TNF monotherapy (n=25), or anti-TNF combined with MTX (n=10) for active disease. Patients were consecutively recruited from the existing PSoriatic arthritis, Ankylosing spondylitis, Rheumatoid Arthritis (PSARA) study.2 Baseline data were compared with clinical information obtained 6 weeks and 6 months after treatment initiation. Complement activation was assessed by measuring soluble terminal complement complex (sC5b-9) levels at each point. Inflammation was determined from erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, and endothelial function was measured by finger plethysmography.

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A total of 51 patients with SpA were examined, among whom 31 had psoriatic arthritis (PsA) and 20 had ankylosing spondylitis (AS). Median sC5b-9 levels (0.7 Clinical Assessment Unit [CAU]/mL at baseline) decreased significantly from baseline to 6 weeks in the total cohort (mean differencebase-6 weeks, 0.14 CAU; 95% CI, 0.07-0.22 CAU; P =.001), with no significant differences observed between diagnostic subgroups. During the period between 6 weeks and 6 months, sC5b-9 levels remained relatively stable in the PsA group and decreased nominally in the AS group. Among patients given anti-TNF with or without MTX, sC5b-9 levels decreased significantly between baseline and 6 weeks.

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Those receiving MTX monotherapy, however, did not experience a statistically significant reduction. During the period between 6 weeks and 6 months, sC5b-9 levels remained stable across all medication subgroups. Reduction in sC5b-9 from baseline to 6 weeks was correlated with decreases in ESR (P =.001) and CRP (P =.002), and increases in high-density cholesterol (P =.01) and total cholesterol (P =.01). In analyses adjusted for age and sex, reduction in sC5b-9 from baseline to 6 weeks was also associated with improved endothelial function (P =.05).

According to these data, anti-TNF treatment was more effective than MTX monotherapy in reducing complement activation in SpA. Investigators hypothesized that the effects of TNF inhibition on complement activation may explain the observed decrease in cardiovascular morbidity among patients given anti-TNF drugs. Further research is necessary to clarify the relationship between complement activation and markers of cardiovascular risk in SpA.


1. Hokstad I, Deyab G, Fagerland MW, et al. Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: an observational study [published online July 23, 2019]. PLOS One. doi:10.1371/journal.pone.0220079

2. Deyab G, Hokstad I, Whist, JE, et al. Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. PLOS One. 2017;12(2):e0169830.