Efficacy of anti-tumor necrosis factor therapy for extra-articular manifestations in patients with ankylosing spondylitis: a meta-analysis.

BACKGROUND: We performed a meta-analysis to evaluate the effect of anti-tumor necrosis factor (TNF) therapy on the frequency of extra-articular manifestations (EAMs) in patients with ankylosing spondylitis (AS). METHODS: We searched with the terms 'ankylosing spondylitis', 'infliximab', 'etanercept', 'adalimumab', 'golimumab', 'certolizumab', 'TNF inhibitor/blocker/antagonists' or 'anti-TNF' on MEDLINE, EMBASE and Cochrane Library for randomized controlled trials (RCTs) of ≥ 12 weeks with parallel or crossover design of TNF inhibitor versus placebo to treat uveitis, inflammatory bowel disease (IBD) and/or psoriasis of AS, published before February 2014. RESULTS: We found 8 RCTs that fit our criteria. Anti-TNF therapy was associated with less uveitis than placebo in patients with AS (OR: 0.35, 95% CI: 0.15-0.81, P = 0.01). Subgroup analysis showed receptor fusion proteins were more efficacious for uveitis than placebo (OR: 0.30, 95% CI: 0.09-0.94, P = 0.04), but monoclonal antibodies were not (OR: 0.43, 95% CI: 0.12-1.49, P = 0.18). Anti-TNF therapy and placebo group did not significantly differ in treating IBD in AS patients (OR: 0.75, 95% CI: 0.25-2.29, P = 0.61). In subgroup analysis, neither monoclonal antibodies (OR: 0.45, 95% CI: 0.10-1.92, P = 0.28) nor receptor fusion proteins (OR: 1.52, 95% CI: 0.25-9.25, P = 0.65) significantly differed from placebo in treating IBD. We found no suitable reports on psoriasis. CONCLUSIONS: Anti-TNF therapy was preventive for flares or new onset of uveitis in AS patients, and might be an alternative for these patients. However, monoclonal anti-TNF antibodies and TNF receptor fusion proteins were not efficacious for IBD in AS patients.

Meta-analysis of IL-17 inhibitors in two populations of rheumatoid arthritis patients: biologic-naïve or tumor necrosis factor inhibitor inadequate responders.

OBJECTIVES: To evaluate the efficacy and safety of interleukin 17 (IL-17) inhibitors in two rheumatoid arthritis (RA) populations: biologic-naïve or tumor necrosis factor inhibitor inadequate responders (TNF-IR). METHOD: A systematic search was performed in major electronic databases to identify relevant randomized controlled trials (RCTs) reporting the American College of Rheumatology 20% (ACR20), ACR50, ACR70 responses and adverse events (AEs) of IL-17 inhibitors versus placebo in patients with RA. We divided these patients into two subgroups: biologic-naïve or TNF-IR. The meta-analysis was performed using Review Manager 5.3 software. Results were expressed as risk ratio (RR) with pertinent 95% confidence interval (95% CI). RESULTS: Ten studies with a total of 2499 patients were included. For biologic-naïve patients, ACR50 and ACR70 responses were significantly better with IL-17 inhibitors than placebo (RR = 1.71, 95% CI 1.23-2.38, P = 0.001 and RR = 2.63, 95% CI 1.10-6.25, P = 0.03, respectively), but ACR20 responses for IL-17 inhibitors were not statistically superior to placebo (RR = 1.34, 95% CI 0.94-1.91, P = 0.11). For TNF-IR, IL-17 inhibitors were effective in achieving ACR20 (RR = 1.67, 95% CI 1.40-2.00, P < 0.00001), ACR50 (RR = 1.94, 95% CI 1.43-2.63, P < 0.0001), and ACR70 (RR = 2.11, 95% CI 1.26-3.55, P = 0.005) compared to placebo. In the safety analysis, IL-17 inhibitors did not show increased risk of any AEs by comparing to placebo in both biologic-naïve patients and TNF-IR. CONCLUSION: IL-17 inhibitors were effective in the treatment of RA without increased risk of AEs, whether for biologic-naïve patients or TNF-IR. Key Points • In this meta-analysis comparing IL-17 inhibitors with placebo in 2499 rheumatoid arthritis patients, IL-17 inhibitors improved ACR50 and ACR70, but not ACR20, responses in biologic-naïve patients. • IL-17 inhibitors improved ACR20, ACR50, and ACR70 responses in tumor necrosis factor inhibitor inadequate responders.

Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis.

BACKGROUND: Interleukin-23 (IL-23) is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis (RA), and to determine the relationship between the IL-23 level and disease activity in RA patients. METHODS: Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), C-reactive protein (CRP), rheumatoid factor (RF) levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA). The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. RESULTS: The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. CONCLUSIONS: The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.