title: Effectiveness of Tumor Necrosis Factor Inhibitors in Combination with Various csDMARD in the Treatment of Rheumatoid Arthritis: Data from the DREAM Registry.
abstract: To analyze and compare the effectiveness and drug survival in patients with rheumatoid arthritis, as measured by 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire-Disability Index (HAQ-DI), of tumor necrosis factor inhibitor (TNFi) monotherapy, TNFi + leflunomide (LEF), TNFi + sulfasalazine (SSZ), TNFi + other conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and TNFi + methotrexate (MTX) therapy, in daily practice.
  
  
  
  Data were collected from the DREAM registry. Patients beginning their first TNFi treatment were included in the study: TNFi monotherapy (n = 320), TNFi + SSZ (n = 103), TNFi + LEF (n = 80), TNFi + other csDMARD (n = 99), TNFi + MTX alone (n = 919), TNFi + MTX + other csDMARD (n = 412). Treatment effectiveness was analyzed using DAS28 and HAQ-DI with linear mixed models and the TNFi drug survival was analyzed using Kaplan-Meier curves and Cox regression. All analyses have been corrected for confounders.
  
  
  
  The patients who received TNFi + MTX had significantly better DAS28 and HAQ-DI values over time (both p < 0.001) and longer TNFi drug survival than TNFi monotherapy (p < 0.001). TNFi + SSZ and TNFi + other csDMARD had significantly better DAS28 values over time (p = 0.001) and longer drug survival (p = 0.001) versus TNFi monotherapy. TNFi + LEF was not significantly better compared to monotherapy. Adding other csDMARD to the TNFi + MTX combination provided no added value.
  
  
  
  Preferably, TNFi should be prescribed together with MTX. If this is not possible, we advise the use of other csDMARD.
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center. sofie.manders@radboudumc.nl.
authors.forename: Sofie H M
authors.initials: SH
authors.lastname: Manders
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Wietske
authors.initials: W
authors.lastname: Kievit
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Tim L T A
authors.initials: TL
authors.lastname: Jansen
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Jan N
authors.initials: JN
authors.lastname: Stolk
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Henk
authors.initials: H
authors.lastname: Visser
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Annemarie M
authors.initials: AM
authors.lastname: Schilder
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Harald E
authors.initials: HE
authors.lastname: Vonkeman
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Eddy
authors.initials: E
authors.lastname: Adang
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Mart A F J
authors.initials: MA
authors.lastname: van de Laar
authors.affiliation: From the Department of IQ Healthcare, the Department of Health Evidence, the Department of Rheumatic Diseases, Radboud University Medical Center, Nijmegen; Rheumatology, Ziekenhuis Gelderse Vallei, Ede; Rheumatology, Rijnstate, Arnhem; Rheumatology, Medical Centre Leeuwarden, Leeuwarden; Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente, Enschede, the Netherlands.S.H. Manders, MSc, Department of IQ Healthcare, Radboud University Medical Center; W. Kievit, PhD, Department of Health Evidence, Radboud University Medical Center; T.L. Jansen, PhD, Department of Rheumatic Diseases, Radboud University Medical Center; J.N. Stolk, PhD, Rheumatology, Ziekenhuis Gelderse Vallei; H. Visser, PhD, Rheumatology, Rijnstate; A.M. Schilder, MD, Rheumatology, Medical Centre Leeuwarden; H.E. Vonkeman, PhD, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; E. Adang, PhD, Department of Health Evidence, Radboud University Medical Center; M.A. van de Laar, Professor, Arthritis Centre Twente, Rheumatology and Clinical Immunology, Medical Spectrum Twente; P.L. van Riel, Professor, Department of IQ Healthcare, Radboud University Medical Center.
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012042:Registries; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: DISEASE-MODIFYING ANTIRHEUMATIC DRUGS; METHOTREXATE; RHEUMATOID ARTHRITIS; TUMOR NECROSIS FACTOR INHIBITOR