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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial.
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.
Afiliação
  • Hetland ML; Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark merete.hetland@dadlnet.dk.
  • Haavardsholm EA; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Rudin A; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Nordström D; Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Nurmohamed M; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Gothenburg, Sweden.
  • Gudbjornsson B; Division of Rheumatology, Helsinki University Hospital, Helsinki, Finland.
  • Lampa J; University of Helsinki, Helsinki, Finland.
  • Hørslev-Petersen K; Amsterdam Rheumatology and Immunology Center, Reade, Netherlands.
  • Uhlig T; Department of Rheumatology and Amsterdam Rheumatology Center, Amsterdam University Medical Centers, Amsterdam, Netherlands.
  • Grondal G; Landspitali University Hospital, Reykjavik, Iceland.
  • Østergaard M; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Heiberg MS; Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Twisk J; Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.
  • Lend K; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
  • Krabbe S; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Hyldstrup LH; University of Oslo, Oslo, Norway.
  • Lindqvist J; Landspitali University Hospital, Reykjavik, Iceland.
  • Hultgård Ekwall AK; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Grøn KL; Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
  • Kapetanovic M; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Faustini F; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
  • Tuompo R; Department of Epidemiology and Biostatistics, Amsterdam University Medical Centres, Amsterdam, Netherlands.
  • Lorenzen T; Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Cagnotto G; Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
  • Baecklund E; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Hendricks O; Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
  • Vedder D; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Sokka-Isler T; Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Husmark T; Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Ljoså MA; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy of University of Gothenburg, Gothenburg, Sweden.
  • Brodin E; Copenhagen Center for Arthritis Research (COPECARE) and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
  • Ellingsen T; Section of Rheumatology, Department of Clinical Sciences Lund, Skåne University Hospital, Lund and Malmö, Sweden.
  • Söderbergh A; Department of Medicine, Rheumatology Unit, Center for Molecular Medicine (CMM), Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Rizk M; Division of Rheumatology, Helsinki University Hospital, Helsinki, Finland.
  • Olsson ÅR; University of Helsinki, Helsinki, Finland.
  • Larsson P; Department of Rheumatology, Silkeborg University Clinic, Silkeborg, Denmark.
  • Uhrenholt L; Department of Rheumatology, Skåne University Hospital, Malmö, Sweden.
  • Just SA; Rheumatology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
  • Stevens DJ; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Laurberg TB; Danish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.
  • Bakland G; Amsterdam Rheumatology and Immunology Center, Reade, Netherlands.
  • Olsen IC; Department of Medicine and University of Eastern Finland, Jyväskylä Central Hospital, Jyväskylä, Finland.
  • van Vollenhoven R; Department of Rheumatology, Falu Hospital, Falun, Sweden.
BMJ ; 371: m4328, 2020 12 02.
Article em En | MEDLINE | ID: mdl-33268527
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%) 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Produtos Biológicos / Metotrexato / Antirreumáticos / Glucocorticoides Tipo de estudo: Clinical_trials / Guideline Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: BMJ Assunto da revista: MEDICINA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Dinamarca País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Produtos Biológicos / Metotrexato / Antirreumáticos / Glucocorticoides Tipo de estudo: Clinical_trials / Guideline Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: BMJ Assunto da revista: MEDICINA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Dinamarca País de publicação: Reino Unido