Abatacept and certolizumab pegol treatment among patients with early rheumatoid arthritis (RA) demonstrated superior clinical remission rates compared with active conventional therapy, according to study findings published in Annals of the Rheumatic Diseases.
Debate over optimal first-line treatment in early RA is ongoing. US and European agencies recommend conventional synthetic disease-modifying antirheumatic drugs combined with methotrexate (MTX).
Investigators compared clinical and radiographic outcomes of biological therapies vs active conventional therapy for treatment of patients with early RA.
The investigator-initiated, open-label, controlled, assessor-blinded Nordic Rheumatic Diseases Strategy Trials and Registries (NORD-STAR) study (ClinicalTrials.gov Identifier: NCT01491815) was conducted from December 2012 to December 2018 at 29 sites across 6 countries.
The study included patients with treatment-naïve, moderate/severe early RA randomly assigned 1:1:1:1 to one of 4 treatment arms: (1) active conventional therapy (oral prednisolone tapered quickly and discontinued at week 36 or sulfasalazine, hydroxychloroquine, and intra articular glucocorticoid injections in swollen joints), (2) abatacept, (3) certolizumab pegol, or (4) tocilizumab. All 4 treatments were combined with MTX.
Week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score were the primary outcomes.
A total of 812 patients underwent randomization and 625 completed the 48 weeks of follow-up. Sixty-nine percent of patients were women with a mean time from diagnosis to treatment of 14 days.
At week 48, adjusted CDAI remission rates were 59.3% for abatacept, 52.3% for certolizumab pegol, 51.9% for tocilizumab, and 39.2% for active conventional therapy.
Compared with conventional therapy, remission rates were significantly higher for abatacept (adjusted difference [AD], +20.1%; P <.001) and certolizumab pegol (AD, +13.1%; P =.021) but not for tocilizumab (AD, +12.7%; P =.030), when applying a significance level of 0.025.
Investigators noted week 48 CDAI remission was consistently better in the biological groups, while radiographic progression was low with no between-group differences.
Week 24 clinical results showed active conventional therapy being noninferior to certolizumab pegol and to tocilizumab. Week 48 results were significantly improved compared with week 24 results for the biological therapies.
This increasing difference in CDAI remission rates is accounted for by the active conventional therapy group remission rate decline from week 24 to week 48 (42.7% vs 39.2%) and the increase in CDAI remission rates from week 24 to week 48 for abatacept (52.0% vs 59.3%), certolizumab pegol (46.5% vs 52.3%), and tocilizumab (42.1% vs 51.9%).
Investigators detected no new safety indications.
Study limitations included the open-label design and underpowered sample size for subgroup analyses.
The study authors concluded, “Biological therapies are more costly than conventional therapy. Nevertheless, using a biological therapy as first-line therapy—after demonstration of clinical superiority—may be justified by the high direct and indirect costs of poorly controlled RA.”
“The cost-effectiveness should be confirmed in a dedicated analysis,” they added.
Disclosure: This research was supported by Union Chimique Belge and Bristol Myers Squibb. One or more study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Østergaard M, van Vollenhoven RF, Rudin A, et al; NORD-STAR study group. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomized controlled NORD-STAR trial. Ann Rheum Dis. Published online July 9, 2023. doi:10.1136/ard-2023-224116