TY - JOUR
T1 - Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis
T2 - 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial
AU - Østergaard, Mikkel
AU - van Vollenhoven, Ronald F.
AU - Rudin, Anna
AU - Hetland, Merete Lund
AU - Heiberg, Marte Schrumpf
AU - Nordström, Dan C.
AU - Nurmohamed, Michael T.
AU - Gudbjornsson, Bjorn
AU - Ørnbjerg, Lykke Midtbøll
AU - Bøyesen, Pernille
AU - Lend, Kristina
AU - Hørslev-Petersen, Kim
AU - Uhlig, Till
AU - Sokka, Tuulikki
AU - Grondal, Gerdur
AU - Krabbe, Simon
AU - Lindqvist, Joakim
AU - Gjertsson, Inger
AU - Glinatsi, Daniel
AU - Kapetanovic, Meliha Crnkic
AU - Aga, Anna-Birgitte
AU - Faustini, Francesca
AU - Parmanne, Pinja
AU - Lorenzen, Tove
AU - Giovanni, Cagnotto
AU - Back, Johan
AU - Hendricks, Oliver
AU - Vedder, Daisy
AU - Rannio, Tuomas
AU - Grenholm, Emma
AU - Ljoså, Maud Kristine
AU - Brodin, Eli
AU - Lindegaard, Hanne
AU - Söderbergh, Annika
AU - Rizk, Milad
AU - Kastbom, Alf
AU - Larsson, Per
AU - Uhrenholt, Line
AU - Just, S. ren Andreas
AU - Stevens, David J.
AU - Bay Laurbjerg, Trine
AU - Bakland, Gunnstein
AU - Olsen, Inge Christoffer
AU - Haavardsholm, Espen A.
AU - Lampa, Jon
N1 - Funding Information:
Funding was obtained through public sources: Academy of Finland (grant number 258536), Finska Läkaresällskapet, grant from the South-Eastern Health Region, Norway, HUCH Institutional grant, Finland (grant number 1159005), Icelandic Society for Rheumatology, interregional grant from all health regions in Norway, NordForsk (grant number 70945), Regionernes Medicinpulje, Denmark (grant numbesr 14/217), Stockholm County Council, Sweden (grant number 20100490), Swedish Medical Research Council (grant numbers C0634901, D0342301 and 2015- 00891_5), Swedish Rheumatism Association and The Research Fund of University Hospital, Reykjavik, Iceland (grant number A2015017). UCB supported the work in the context of an investigator-initiated study where UCB provided certolizumab pegol at no cost. UCB had no role in study design, collection, analysis and interpretation of data, in the writing of the report or in the decision to submit for publication. Bristol Myers Squibb (BMS) provided abatacept at no cost. In addition, the Karolinska Institute received several unrestricted grants from BMS; these were subsequently transferred to the principal investigators of Denmark, Finland and the Netherlands to help defray various trial-related costs at the local level. BMS had no role in study design, collection, analysis and interpretation of data, in the writing of the report or in the decision to submit for publication. The final manuscript was provided for courtesy review to UCB and BMS in line with Good Publication Practice We confirm the independence of researchers from funders and that all authors, external and internal, had full access to all of the data (including statistical reports and tables) in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Abatacept
KW - Biological Therapy
KW - Certolizumab pegol
KW - Methotrexate
KW - Rheumatoid Arthritis
UR - https://www.scopus.com/pages/publications/85165210988
U2 - 10.1136/ard-2023-224116
DO - 10.1136/ard-2023-224116
M3 - Article
C2 - 37423647
SN - 0003-4967
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
ER -