Conventional Therapy Appears as Effective as Most Biologics for Early Rheumatoid Arthritis

Conventional treatment for rheumatoid arthritis (RA) is not inferior to treatment with either of the biologics certolizumab pegol or tocilizumab, but has less impact on disease activity than abatacept, shows a recent study published in the BMJ.¹ The study is the first randomized trial to examine the comparative benefits and safety of biological drugs with different modes of action versus active conventional treatment.

Current guidelines recommend early rheumatoid arthritis is treated with conventional slow-acting synthetic disease-modifying drugs, but the availability of a variety of biological disease-modifying drugs with different modes of action has raised questions over whether the conventional therapy remains the best approach.

Recognizing the need for more research, a consortium of Scandinavian and Dutch academic investigators designed a randomized trial (NOrdic Rheumatic Diseases Strategy Trials And Registries [NORD-STAR] study) to compare the benefits and safety of active conventional treatment plus 1 of 3 biological treatments combined with methotrexate in treatment-naïve patients.

Conventional treatment was either methotrexate combined with oral prednisolone or methotrexate combined with sulfasalazine, hydroxychloroquine, and intra-articular triamcinolone hexacetonide intraarticular corticosteroids. The 3 biological treatments were: a tumor necrosis factor inhibitor (certolizumab pegol), a T cell costimulation blocker (abatacept), and an interleukin 6 inhibitor (tocilizumab).

A total of 812 patients from 29 rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland were randomized 1:1:1:1 to the 4 treatments between 2012 and 2018. At the start of the study patients’ baseline disease activity score for 28 joints was 5.0 (standard deviation 1.1) and patients were re-assessed after 24 weeks.

Merete Hetland, DMSc, PhD, MD

“This study is the first randomized trial examining the comparative benefits and safety of biological drugs with different modes of action versus active conventional treatment in treatment naïve patients with rheumatoid arthritis and we were surprised to see that active conventional therapy had responses similar to those of the three different biologics,” said Merete Hetland, DMSc, PhD, MD, professor of rheumatology at the Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.

“After 24 weeks, clinical disease activity index remission was achieved in > 40% of patients with early RA, whether treated with biologics combined with methotrexate (TNF inhibitor, abatacept or IL6-inhibitor) or active conventional therapy (methotrexate, bridging glucocorticoids, and in some patients also sulfasalazine and hydroxychloroquine). Abatacept performed 9% better, whereas for all key secondary outcomes the overall differences between treatments were modest with overlapping confidence intervals.” Secondary outcomes included clinical disease activity index remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms.

After 24 weeks treatment, adjusted clinical disease activity index remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (95% confidence interval 39.9% to 53.1%) for certolizumab pegol, 52.0% (95% confidence interval 45.5% to 58.6%) for abatacept, and 42.1% (95% confidence interval 35.3% to 48.8%) for tocilizumab.

The absolute differences clinical disease activity index remission rates between conventional therapy and the biologics were 3.9% (95% confidence interval −5.5% to 13.2%) for certolizumab pegol, 9.4% (95% confidence interval 0.1% to 18.7%) for abatacept, and −0.6% (95% confidence interval −10.1% to 8.9%) for tocilizumab.

Asked whether treatment recommendations need to be updated to reflect the findings, Hetland said: “We are currently awaiting the primary radiographic outcomes at 48 weeks as well as a number of spin-off studies of a range of biomarkers that may assist us (and clinicians) in a more personalized treatment strategy for early rheumatoid arthritis patients.”

Reference:

Hetland ML, Haavardsholm EA, Rudin A, et al. Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial. BMJ. 2020;371:m4328. Published 2020 Dec 2. doi:10.1136/bmj.m4328