Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial.

• Published in: BMJ
• Main Authors: Hetland, Merete Lund, Haavardsholm, Espen A, Rudin, Anna, Nordström, Dan, Nurmohamed, Michael, Gudbjornsson, Bjorn, Lampa, Jon, Hørslev-Petersen, Kim, Uhlig, Till, Grondal, Gerdur, Østergaard, Mikkel, Heiberg, Marte S, Twisk, Jos, Lend, Kristina, Krabbe, Simon, Hyldstrup, Lise Hejl, Lindqvist, Joakim, Hultgård Ekwall, Anna-Karin, Grøn, Kathrine Lederballe, Kapetanovic, Meliha, Faustini, Francesca, Tuompo, Riitta, Lorenzen, Tove, Cagnotto, Giovanni, Baecklund, Eva, Hendricks, Oliver, Vedder, Daisy, Sokka-Isler, Tuulikki, Husmark, Tomas, Ljoså, Maud-Kristine Aga, Brodin, Eli, Ellingsen, Torkell, Söderbergh, Annika, Rizk, Milad, Olsson, Åsa Reckner, Larsson, Per, Uhrenholt, Line, Just, Søren Andreas, Stevens, David John, Laurberg, Trine Bay, Bakland, Gunnstein, Olsen, Inge C, van Vollenhoven, Ronald
• Other Authors: 1Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark [e-mail]. 2Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. 3Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. 4Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden. 5Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Gothenburg, Sweden. 6Division of Rheumatology, Helsinki University Hospital, Helsinki, Finland. 7University of Helsinki, Helsinki, Finland. 8Amsterdam Rheumatology and Immunology Center, Reade, Netherlands. 9Department of Rheumatology and Amsterdam Rheumatology Center, Amsterdam University Medical Centers, Amsterdam, Netherlands. 10Landspitali University Hospital, Reykjavik, Iceland. 11Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 12Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. 13Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark. 14Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. 15University of Oslo, Oslo, Norway. 16Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark. 17Department of Epidemiology and Biostatistics, Amsterdam University Medical Centres, Amsterdam, Netherlands. 18Section of Rheumatology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund and Malmö, Sweden. 19Department of Rheumatology, Silkeborg University Clinic, Silkeborg, Denmark. 20Department of Rheumatology, Skåne University Hospital, Malmö, Sweden. 21Rheumatology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. 22Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 23Department of Medicine and University of Eastern Finland, Jyväskylä Central Hospital, Jyväskylä, Finland. 24Department of Rheumatology, Falu Hospital, Falun, Sweden. 25Department of Rheumatology, Ålesund Hospital, Ålesund, Norway. 26Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. 27Rheumatology Research Unit, Odense University Hospital, Southern University of Denmark, Denmark. 28Department of Rheumatology, Örebro University Hospital, Örebro, Sweden. 29Rheumatology Clinic, Västmanlands Hospital Västerås, Sweden. 30Department of Rheumatology, Linköping University Hospital, Sweden. 31Academic Specialist Center, Stockholm, Sweden. 32Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark. 33Section of Rheumatology, Department of Medicine, Svendborg Hospital OUH, Denmark. 34Department of Rheumatology, St Olav's Hospital, University Hospital of Trondheim, Trondheim, Norway. 35Department of Rheumatology, Aarhus University Hospital, Denmark. 36Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway. 37Department of Research Support for Clinical Trials, Oslo University Hospital, Norway.
• Format: Article in Journal/Newspaper
• Language: English
• Published: British Medical Association 2021
• Subjects: Líftæknilyf; Iktsýki; Biological Products; Arthritis; Rheumatoid; Norway; Iceland
• Online Access: http://hdl.handle.net/2336/621628; https://doi.org/10.1136/bmj.m4328

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download Objective: To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. Design: Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. Setting: Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. Participants: Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. Interventions: Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. Main outcome measures: The primary outcome was adjusted clinical disease activity index remission (CDAI≤2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. Results: 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for ...