Active conventional treatment and three different biological treatments in early rheumatoid arthritis : Phase IV investigator initiated, randomised, observer blinded clinical trial
(2020) In The BMJ 371.- Abstract
AbstractObjective 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,... (More)
AbstractObjective 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%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. Conclusions All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis. Trial registration EudraCT2011-004720-35, NCT01491815.
(Less)
- author
- 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
LU
; Faustini, Francesca
; Tuompo, Riitta
; Lorenzen, Tove
; Cagnotto, Giovanni
LU
; 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.
and Van Vollenhoven, Ronald
(Less) - organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The BMJ
- volume
- 371
- article number
- m4328
- publisher
- BMJ Publishing Group
- external identifiers
-
- scopus:85097120848
- pmid:33268527
- ISSN
- 0959-8146
- DOI
- 10.1136/bmj.m4328
- language
- English
- LU publication?
- yes
- id
- 2cc8083a-7a00-4896-933e-ea30bab2d35f
- date added to LUP
- 2020-12-15 07:20:54
- date last changed
- 2024-04-17 21:52:14
@article{2cc8083a-7a00-4896-933e-ea30bab2d35f,
abstract = {{<p>AbstractObjective 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%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. Conclusions All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis. Trial registration EudraCT2011-004720-35, NCT01491815. </p>}},
author = {{Hetland, Merete Lund and Haavardsholm, Espen A. and Rudin, Anna and Nordström, Dan and Nurmohamed, Michael and Gudbjornsson, Bjorn and Lampa, Jon and Hørslev-Petersen, Kim and Uhlig, Till and Grondal, Gerdur and Østergaard, Mikkel and Heiberg, Marte S. and Twisk, Jos and Lend, Kristina and Krabbe, Simon and Hyldstrup, Lise Hejl and Lindqvist, Joakim and Hultgård Ekwall, Anna Karin and Grøn, Kathrine Lederballe and Kapetanovic, Meliha and Faustini, Francesca and Tuompo, Riitta and Lorenzen, Tove and Cagnotto, Giovanni and Baecklund, Eva and Hendricks, Oliver and Vedder, Daisy and Sokka-Isler, Tuulikki and Husmark, Tomas and Ljoså, Maud Kristine Aga and Brodin, Eli and Ellingsen, Torkell and Söderbergh, Annika and Rizk, Milad and Olsson, Åsa Reckner and Larsson, Per and Uhrenholt, Line and Just, Søren Andreas and Stevens, David John and Laurberg, Trine Bay and Bakland, Gunnstein and Olsen, Inge C. and Van Vollenhoven, Ronald}},
issn = {{0959-8146}},
language = {{eng}},
publisher = {{BMJ Publishing Group}},
series = {{The BMJ}},
title = {{Active conventional treatment and three different biological treatments in early rheumatoid arthritis : Phase IV investigator initiated, randomised, observer blinded clinical trial}},
url = {{http://dx.doi.org/10.1136/bmj.m4328}},
doi = {{10.1136/bmj.m4328}},
volume = {{371}},
year = {{2020}},
}