Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rheumatoid Arthritis—A Network Meta-Analysis of 36 Randomized Controlled Trials

Abstract

The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network. The previously untested comparison with placebo was performed to estimate not only the effect relative to another drug, but also the absolute attainable effect. Compared to placebo there was a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab, certolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per year when combined with MTX. Although significantly better than MTX and placebo, golimumab seemed inferior to the remaining TNFis. There was no difference between original reference drugs (Remicade, Enbrel) and the almost identical copy drugs (biosimilars).

Efficacy, safety and immunogenicity of etanercept biosimilars versus reference biologics in patients with rheumatoid arthritis: A meta-analysis

“…Before our study, there was a network meta-analysis which only included three etanercept biosimilars from three RCTs, indicated that no significant differences was found between etanercept biosimilars and etanercept originators in patients with RA despite treatment with MTX in terms of ACR20 response rate and incidence of serious adverse events, which was consistent with our findings ( Lee and Song, 2021 ). Furthermore, some systematic literature reviews or network meta-analyses evaluated the efficacy and safety of tumor necrosis factor (TNF) inhibitors biosimilars versus TNF inhibitors originators, demonstrated that these biosimilars had an overall comparable efficacy and safety profile compared with their originators in RA patients, which was also similar to what we found ( Komaki et al, 2017 ; Moots et al, 2018 ; Graudal et al, 2019 ; Ho Lee and Gyu Song, 2021 ). Nevertheless, theses previous related studies have some weakness, such as limited outcome indicators, failure to consider different time points and a lack of evidence assessment.…”

Biological Therapy in Patients with Rheumatoid Arthritis in a Tertiary Center in Portugal: A Cross-Sectional Study

“…22,23 In our cohort, a high-risk group of patients, with a potentially productive work-life, initiation of bDMARD occurred at a median of four years after RA onset. A recent meta-analysis of 36 randomized clinical trials comparing the standard doses of the five anti-TNF inhibitors combined with MTX with MTX monotherapy described trial participants with a mean age varying from 48.4 to 60.7 years and a mean duration of disease from 0.2 to 11 years, 24 effectively meaning that the median therapeutic delay of four years, in our patient population, is probably not that prolonged when compared to others. Lack of access to specialist care may significantly contribute to the therapeutic delay.…”

Subcutaneously-Administered Infliximab in the Management of Rheumatoid Arthritis: A Short Narrative Review of Current Clinical Evidence

“…However, these results should be interpreted with caution, as results from other meta-analyses indicate a substantially similar efficacy profile of the different TNF inhibitors in the treatment of RA. 32 …”