Dose reduction of recombinant human tumor necrosis factor inhibitors (etanercept) can be effective in ankylosing spondylitis patients with synovitis of the hip in a Chinese population

Abstract

Ankylosing spondylitis (AS) is an immune-mediated inflammatory arthritis and enthesitis involving the spine and peripheral joints. In recent years, specific antagonist of tumor necrosis factor (anti-TNFα, etanercept) 50 mg weekly therapy has rapidly gained popularity for the treatment of AS. However, the dose of etanercept has not been determined in Asian, particularly Chinese populations. The purpose of the study was to evaluate the efficacy and safety of dose reduction of etanercept (50 mg/week in 4 weeks followed by 25 mg/week in 8 weeks) in the treatment of AS with synovitis of the hip, as against the conventional dose (50 mg/week in 12 weeks) in a Chinese population. Forty-three Chinese AS patients with synovitis of the hip were involved in this study. Seventeen of them were randomized to receive conventional dose of etanercept treatment and 26 were given a dose reduction regimen for 12 weeks. The primary efficacy endpoint was disease activity of response for AS at week 12, including Bath AS Disease Activity Index (BASDAI), the serum erythrocyte sediment rate (ESR), C-reactive protein (CRP), and assessment of synovitis of the hip by ultrasonography. At 12 weeks, all of the patients had responses to some extent and the efficacy variables improved significantly over time, but not between treatment groups. Nine patients experienced at least one adverse event (generally, infections and injection site reactions), most of them mild or moderate. In sum, the dose reduction of etanercept regimen in the 12-week AS treatment was confirmed as a safe and effective therapy as the conventional dose was given.

Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

“…Disease duration ranged, where reported, with a median of 12 years. Two studies (37,38) included patients who were naive to TNFi therapy. One study investigated full discontinuation of TNFi (39) as a method of reduction, and the remaining 5 studies incorporated either a reduced dose (40,41) or an extended dosing interval (37,38,40,42) of the TNFi (see Table 2 for TNFi regimens).…”

“…One study investigated full discontinuation of TNFi (39) as a method of reduction, and the remaining 5 studies incorporated either a reduced dose (40,41) or an extended dosing interval (37,38,40,42) of the TNFi (see Table 2 for TNFi regimens). Three studies used etanercept (38,41,42), one used infliximab (37), one used adalimumab (39), and one used any of adalimumab, etanercept, golimumab, and infliximab (40), which could not be separated out by outcome. The studies were conducted primarily in Europe (France, Italy, Spain, and the UK), one in China, and there was one large multinational trial.…”

“…Except for one double‐blind study (39), the remaining studies were open‐label designs, and blinding of outcome assessment, participants, and personnel was judged to have the highest risk of bias. Methods for random sequence generation and allocation concealment were not reported in 2 studies (38,42). Additionally, many outcomes (e.g., adverse events, ASAS40, and BASDAI score, some of which can be included in the criteria for remission/relapse) were subjectively measured.…”

“…Four studies reported on the BASDAI, but one study was omitted from the analysis due to the presence of skewed data (e.g., large SDs) (41). Three studies with 272 participants were included in the analysis (37,38,42). Compared to the standard dose, there was a mean increase in BASDAI score with the reduced dose (MD 0.35 [95% CI 0.10, 0.60]) and low heterogeneity (I 2 = 0%) (see Supplementary Figure , available on the Arthritis Care & Research website at http://onlinelibrary.wiley.com/doi/10.1002/acr.24184/abstract).…”

“…Four studies reported on CRP level, but 2 studies were omitted from the analysis due to skewed data (37,41). Due to high heterogeneity (I 2 = 77.5%), the remaining 2 studies with 86 participants were not pooled (38,42). Upon visual inspection, studies appeared inconsistent in their results, with a mean increase (MD 0.63 [95% CI 0.01, 1.24]) with the reduced dose in one study, and no difference (MD –0.31 [95% CI –0.92, 0.31]) between groups in the other study.…”