1. Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.
- Author
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Østergaard M, van Vollenhoven RF, Rudin A, Hetland ML, Heiberg MS, Nordström DC, Nurmohamed MT, Gudbjornsson B, Ørnbjerg LM, Bøyesen P, Lend K, Hørslev-Petersen K, Uhlig T, Sokka T, Grondal G, Krabbe S, Lindqvist J, Gjertsson I, Glinatsi D, Kapetanovic MC, Aga AB, Faustini F, Parmanne P, Lorenzen T, Giovanni C, Back J, Hendricks O, Vedder D, Rannio T, Grenholm E, Ljoså MK, Brodin E, Lindegaard H, Söderbergh A, Rizk M, Kastbom A, Larsson P, Uhrenholt L, Just SA, Stevens DJ, Bay Laurbjerg T, Bakland G, Olsen IC, Haavardsholm EA, and Lampa J
- Subjects
- Humans, Certolizumab Pegol therapeutic use, Abatacept therapeutic use, Methotrexate therapeutic use, Drug Therapy, Combination, Treatment Outcome, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid diagnostic imaging, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid chemically induced
- Abstract
Background: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action., Methods: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025)., Results: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%., Conclusions: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments., Trial Registration Number: NCT01491815., Competing Interests: Competing interests: MØ received the study drug from BMS and UCB; research grants from Abbvie, BMS, Merck, Novartis and UCB; speaker fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz, and UCB; and consultancy fees from Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, MEDAC, Merck, Novartis, Pfizer, Sandoz and UCB. RFvV received the study drug from BMS and UCB; research grants from BMS, GSK, UCB and AstraZeneca; consulting fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB; expert fees from AbbVie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB; and advisory board fees from AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer and UCB. MLH received research grants from AbbVie, Biogen, BMS, Celtrion, Eli Lily, Janssen Biologics B.V., Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis; and institution pay from Pfizer, Medac, AbbVie and Sandoz; chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies; cochairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. DCN received consulting fees from AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB' meeting support from Pfizer; advisory board participation fee from Novartis; and other service fee by BMS. MTN received research grants from AbbVie, BMS, Pfizer, Galapagos, Amgen and Eli Lily. BG received consulting fee from Novartis and honorary lecture payment from Novartis and Nordic-Pharma. IG received royalty fee for book authorship and support for attending meetings by EULAR. DG received advisory board fee from Eli Lily and AbbVie and speakers fee from Eli Lily. A-BA received speakers fee from AbbVie, Eli Lily, Novartis and Pfizer. CG received the study drug from BMS and UCB. MKL received advisory board fee from AbbVie. AS received advisory board fee from GSK (institution pay). LU received speakers fee from Janssen and support for meeting/travel from AbbVie and Eli Lily. DJS received honorarium fee from UCB (not a part of this, unrelated medication). GB received consultancy fee from UCB. ICO received research grants from EU Horizon 2020 and EU Horizon Europe, advisory board participation from IMPRESS-Norway, ALPHA2PREVENT, FLECAPRO and EVOLVD, and meeting/travel support from European Clinical Research Infrastructure Network. The remaining authors declared no disclosures., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
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