Across 36 RCTs, No Difference Between Reference, Biosimilar Anti-TNFs in RA Joint Destruction

For patients with rheumatoid arthritis (RA), avoiding damage to cartilage and bone in the joints is a key consideration for treatment. While anti—tumor necrosis factor (anti-TNF) therapies are used to treat RA and reduce joint destruction, the available anti-TNF agents, both originator and biosimilar, have not been directly compared with one another or with placebo in terms of their impacts on joint damage. A new study, published last week, attempted to address that gap in the literature by conducting a meta-analysis of randomized controlled trials (RCTs).

The investigators compared 5 anti-TNF agents, as well as an untreated placebo control group, using radiographically estimated joint destruction as the primary outcome.

Their literature search arrived at 36 RCTs that were published in 35 papers. The number of patients enrolled in each study ranged from 24 to 1022, and the studies’ durations varied from 0.2 years to 11 years. The anti-TNF therapies included in the studies, with or without methotrexate and at a range of dosages, were adalimumab, certolizumab, reference infliximab, biosimilar infliximab SB2, biosimilar infliximab CT-P13, biosimilar etanercept SB4, reference etanercept, and golimumab. The oral small-molecule drug sulfasalazine and placebo were also investigated.

They found that the difference in annual progression (percentage point) in terms of joint destruction for each of the treatments, compared with methotrexate monotherapy, was as follows for the standard dose in an unadjusted model and in a 4-covariate metaregression (which included normalized Disease Activity Score in a count of 28 joints, normalized radiographic joint score, normalized glucocorticoid treatment, and incomplete outcome), respectively:

• Adalimumab with methotrexate: −0.5 (95% CI, −0.7 to −0.3); −0.6 (95% CI, −0.9 to −0.4)
• Certolizumab with methotrexate: −0.5 (95% CI, −0.7 to −0.3); −0.6 (95% CI, −0.8 to −0.4)
• Biosimilar etanercept SB4 with methotrexate: −0.7 (95% CI, −1.2 to −0.2); −1.0 (95% CI, −1.4 to −0.6)
• Reference etanercept with methotrexate: −0.6 (95% CI, −0.9 to −0.3); −0.9 (95% CI, −1.3 to −0.6)
• Golimumab with methotrexate: −0.2 (95% CI, −0.5 to 0.1); −0.4 (95% CI, −0.8 to −0.0)
• Biosimilar infliximab SB2 with methotrexate: −0.9 (95% CI, −1.4 to −0.4); −1.0 (95% CI, −1.4 to −0.6)
• Biosimilar infliximab CT-P13 with methotrexate: −0.8 (95% CI, −1.3 to −0.3); −0.9 (95% CI, −1.4 to −0.5)
• Reference infliximab with methotrexate: −0.9 (95% CI, −1.2 to −0.6); −1.0 (95% CI, −1.3 to −0.7)
• Sulfasalazine: −0.7 (95% CI, −1.2 to −0.1); −0.8 (95% CI, −1.4 to −0.3)
• Placebo: 0.4 (95% CI, −0.0 to 0.8); 0.2 (95% CI, −0.2 to 0.5)

The authors write that the effects of anti-TNFs on joint destruction in RA “generally are similar and that the effects of biosimilars correspond to the reference drugs. However, the effect of golimumab in the defined standard dose seemed to be inferior.”

Reference

Graudal N, Kaas-Hansen BS, Guski L, Hubeck-Graudal T, Welton NJ, Jürgens G. Different original and biosimilar TNF inhibitors similarly reduce joint destruction in rheumatoid arthritis—a network meta-analysis of 36 randomized controlled trials. Int J Mol Sci. 2019;20(18):4350. doi: 10.3390/ijms20184350.