Safety of tumor necrosis factor-alpha inhibitors for treatment of ankylosing spondylitis

Abstract

Background:Ankylosing spondylitis (AS) is a chronic immune-mediated disease affecting the sacroiliac joints and the spine, manifesting with new bone formation and osteopenia. Five tumor necrosis factor-alpha (TNF-α) inhibitors (infliximab, etanercept, adalimumab, certolizumab, and golimumab) are available for the treatment of AS, however, the results for the safety of TNF-α inhibitors in the treatment of AS are not consistent.Methods:In this study, we conducted a meta-analysis to determine the safety of TNF-α inhibitors compared with placebo in reducing pain, swelling, and inflammation of AS patients. Eight relevant articles including 2049 patients were included for this meta-analysis study. We observed that the incidence of adverse events (RR = 1.22, 95% CI: 1.12–1.33; P = .501, I2 = 0%) and injection-site reaction (RR = 2.93, 95% CI: 2.02–4.23; P = .691, I2 = 0%) in AS patients’ treatment with TNF-α inhibitors was significantly higher than that with placebo.Results:However, there was no significant difference in the incidence of serious adverse event, infection, serious infection, and discontinuations due to adverse event. TNF-α inhibitors may be a promising treatment for AS, but carries an increased incidence rate of adverse events and injection-site reaction.Conclusion:Due to the existence of the unstable factors, further studies need to be done to verify the result of this study.

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

“…In contrast to data from randomized controlled trials of patients with RA treated with TNF inhibitors, which indicate an increased risk of discontinuation due to an AE (odds ratio [OR], 1.23; 95% CI, 1.06‐1.43), most meta‐analyses of randomized controlled trials find no evidence of an increased risk of discontinuation due to an AE in patients with ankylosing spondylitis treated with TNF inhibitors. In analyses by Ma et al (3 studies, 1025 participants; risk ratio [RR], 1.97; 95%CI, 0.56‐6.93), by Machado et al 17 (6 studies, 1875 participants; RR, 0.99; 95%CI, 0.98‐1.01) and the most recent one by Hou et al (10 studies, 2984 participants; OR, 1.55; 95%CI, 0.95‐2.54) discontinuations due to AEs in TNF inhibitors group were not significantly different from those treated with placebo in the control group. Only in a Cochrane review, incorporating data from 16 studies (2623 participants), is there moderate quality evidence of an increase in withdrawals due to AE in the TNF inhibitor group vs placebo (OR, 2.44; 95%CI, 1.26‐4.72), though the absolute increase was small (1%; 95%CI, 0‐2%)…”

“…None of the meta-analyses of randomized controlled trials of patients with ankylosing spondylitis treated with TNF inhibitors showed an increase in infection and serious infection rates after TNF inhibitors (Table 1). [16][17][18]24,25 Calculated incidence of serious infections after TNF inhibitors was low: 1.9/100 patient-years (pyrs). 24 Also, there was no difference in the occurrence of one of the most common types of infections seen after TNF inhibitors: upper respiratory tract infections (RR, 0.98; 95%CI, 0.93-1.02).…”

“…Although 1 meta‐analysis of AEs in ankylosing spondylitis randomized controlled trials (6 studies, 1975 participants) showed an increased risk of overall AEs in the TNF inhibitor–treated group compared to placebo (RR, 1.22; 95%CI, 1.12‐1.33), it was probably due to an increased risk of injection‐site reactions after TNF inhibitor injection (1713 participants; RR, 2.93; 95%CI, 2.02‐4.23), as there was no increase in the rate of infection, serious infection, or serious AE . In fact, all meta‐analyses of randomized controlled trials performed to date demonstrated no significant difference in serious AE rate in a group of patients with ankylosing spondylitis treated with TNF inhibitors.…”

“…None of the meta‐analyses of randomized controlled trials of patients with ankylosing spondylitis treated with TNF inhibitors showed an increase in infection and serious infection rates after TNF inhibitors (Table ) . Calculated incidence of serious infections after TNF inhibitors was low: 1.9/100 patient‐years (pyrs) .…”

“…14 In contrast to data from randomized controlled trials of patients with RA treated with TNF inhibitors, which indicate an increased risk of discontinuation due to an AE (odds ratio [OR], 1.23; 95% CI, 1.06-1.43), 15 most meta-analyses of randomized controlled trials find no evidence of an increased risk of discontinuation due to an AE in patients with ankylosing spondylitis treated with TNF inhibitors. In analyses by Ma et al 16 participants) showed an increased risk of overall AEs in the TNF inhibitor-treated group compared to placebo (RR, 1.22; 95%CI, 1.12-1.33), it was probably due to an increased risk of injection-site reactions after TNF inhibitor injection (1713 participants; RR, 2.93; 95%CI, 2.02-4.23), as there was no increase in the rate of infection, serious infection, or serious AE. 16 In fact, all meta-analyses of randomized controlled trials performed to date demonstrated no significant difference in serious AE rate in a group of patients with ankylosing spondylitis treated with TNF inhibitors.…”