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
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Published:2023-07-09
Issue:10
Volume:82
Page:1286-1295
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ISSN:0003-4967
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Container-title:Annals of the Rheumatic Diseases
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language:en
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Short-container-title:Ann Rheum Dis
Author:
Østergaard MikkelORCID, van Vollenhoven Ronald FORCID, Rudin Anna, Hetland Merete LundORCID, Heiberg Marte Schrumpf, Nordström Dan C, Nurmohamed Michael TORCID, Gudbjornsson Bjorn, Ørnbjerg Lykke MidtbøllORCID, Bøyesen Pernille, Lend Kristina, Hørslev-Petersen Kim, Uhlig TillORCID, Sokka TuulikkiORCID, Grondal Gerdur, Krabbe Simon, Lindqvist Joakim, Gjertsson IngerORCID, Glinatsi Daniel, Kapetanovic Meliha Crnkic, Aga Anna-BirgitteORCID, Faustini Francesca, Parmanne Pinja, Lorenzen Tove, Giovanni Cagnotto, Back Johan, Hendricks Oliver, Vedder DaisyORCID, Rannio Tuomas, Grenholm Emma, Ljoså Maud Kristine, Brodin Eli, Lindegaard Hanne, Söderbergh Annika, Rizk Milad, Kastbom Alf, Larsson Per, Uhrenholt LineORCID, Just Søren AndreasORCID, Stevens David J, Bay Laurbjerg Trine, Bakland Gunnstein, Olsen Inge Christoffer, Haavardsholm Espen A, Lampa Jon
Abstract
BackgroundThe 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.MethodsInvestigator-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)orsulfasalazine, 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).ResultsEight 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%.ConclusionsCompared 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 numberNCT01491815.
Funder
Swedish Medical Research Council Swedish Rheumatism Association Bristol Myers Squibb Academy of Finland Stockholm County Council, Sweden Regionernes Medicinpulje, Danmark UCB Interregional grant from all health regions in Norway University Hospital, Reykjavik, Iceland Finska Läkaresällskapet HUCH Institutional grant NordForsk South-Eastern Health Region, Norway Icelandic Society for Rheumatology
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,Immunology and Allergy,Rheumatology
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