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
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2020
• Subjects: Iceland
• Online Access: https://portal.findresearcher.sdu.dk/da/publications/9beb2b28-b92f-4459-a284-5d12ff057b91; https://doi.org/10.1136/bmj.m4328; https://findresearcher.sdu.dk/ws/files/175132336/bmj.m4328.full.pdf

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 tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) ...