Systematic Review and Meta-Analysis of the Efficacy and Safety of Existing TNF Blocking Agents in Treatment of Rheumatoid Arthritis

Abstract

Background and ObjectivesFive-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT).MethodsA systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.ResultsForty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.ConclusionsNo single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

TNF inhibitor therapy for rheumatoid arthritis

“…Furthermore, anti-TNF-α agents are more efficacious in promoting the clinical signs and symptoms of RA compared to MTX alone. Anti-TNF-α agents plus MTX show sustained efficacy and remain more effective compared to anti-TNF-α monotherapy (53). Compared to MTX and PBO, the ACR20, 50 and 70 response rates for 1-year treatment with MTX plus any of the TNF inhibitors were 60 vs. 25%, 40 vs. 10% and 20 vs. 5%, respectively (54).…”

Biological agents in the treatment of uveitis

“…Moreover, infliximab can induce anti-drug antibodies which can interfere or even abolish the drug effectiveness [6]. As other anti-TNF-α agents, treatment with infliximab is associated with a significant increase of infections, including tuberculosis, bacterial, viral and parasite infections [7]. In 2001, an initial study on the efficacy of anti-TNF-α agents on inflammatory eye diseases was published by Smith et al who showed that both infliximab might benefit certain subgroups of patients with inflammatory eye disease [8].…”

Interleukin-1 Antagonists and Other Cytokine Blockade Strategies for Type 1 Diabetes

“…For many rheumatologic and autoinflammatory diseases, anti-tumor necrosis factor (TNF) α and anti-interleukin (IL) 1 biologics have proven effective in trials conducted over the last decades, and are now registered as first line therapies for many of these disorders [10,11]. In contrast to the situation regarding these autoimmune and inflammatory conditions, clinical testing of cytokine antagonists in T1D is in its infancy, with few reported studies and even fewer ongoing trials, as can be judged by the NIH register of clinical trials,…”

“…Biologic TNFα antagonists include monoclonal antibodies raised against recombinant human TNFα (infliximab, adalimumab, and others) and a recombinant fusion protein between the soluble type 2/p75 TNFα receptor and the constant region of human immunoglobulin G1 (IgG1), termed etanercept [11] (Figure 1). In contrast to the IL-1 family, the TNF family does not include natural TNF receptor antagonists.…”

“…Neutralizing TNFα antagonists are now standard therapy in rheumatology [11]. They are the first biologics of choice because they lead to more rapid pain relief than IL-1 blockers, and have been shown to be equally efficient in terms of the hard endpoint joint space narrowing [18].…”