title: Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study.
abstract: OBJECTIVE
  Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use.
  
  
  METHODS
  Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint (≥20% improvement in American College of Rheumatology (ACR20) criteria at week 14) findings have been reported for all patients in the trial. Reported herein are further assessments of efficacy/safety among patients receiving golimumab+methotrexate (MTX).
  
  
  RESULTS
  Among efficacy-evaluable patients who received MTX at baseline, more receiving golimumab+MTX (n=201) than placebo+MTX (n=103) achieved ACR20 (40.8% vs 14.6%), ACR50 (20.9% vs 3.9%), and ACR70 (11.4% vs 2.9%) responses at week 24. Among the 137 patients who had received only one prior TNF inhibitor (adalimumab, n=33; etanercept, n=47; and infliximab, n=57), week 24 ACR20 rates were 30.3%, 46.8% and 50.9%, respectively, and thus lowest among those who previously used adalimumab. ACR20 response rates were 44.5% (61/137), 36.2% (17/47) and 23.5% (4/17) among patients who had received one, two or three TNF inhibitors, respectively. Adverse event (AE) rates were comparable across type/number of prior anti-TNF agents, but appeared somewhat higher among patients who discontinued previous TNF inhibitor(s) due to intolerance (37/49, 75.5%) versus lack of efficacy (LOE, 113/191, 59.2%).
  
  
  CONCLUSIONS
  Patients with active RA previously treated with ≥1 TNF inhibitor had clinically relevant improvement with golimumab+MTX, which appeared somewhat enhanced among those who received only etanercept or infliximab as their prior TNF inhibitor. Golimumab+MTX safety appeared similar across patients, regardless of TNF inhibitor(s) previously used, with fewer AEs occurring among patients who discontinued prior therapy for LOE.
authors.affiliation: Division of Rheumatology, Department of Medicine III, Medical University of Vienna, and 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kay
authors.affiliation: Division of Rheumatology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
authors.affiliation: Division of Rheumatology, Academic Medical Center, Amsterdam and Atrium Medical Center, Heerlen, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.affiliation: Clinical Immunology, Janssen Research & Development, LLC., Spring House Pennsylvania, USA Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Hsia
authors.affiliation: Biologics Biostatistics, Janssen Research & Development, LLC., Spring House, Pennsylvania, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Xu
authors.affiliation: Biologics Biostatistics, Janssen Research & Development, LLC., Spring House, Pennsylvania, USA.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Translational Medicine Group, Alexion Pharmaceuticals, Cambridge, Massachusetts, USA.
authors.forename: Mittie K
authors.initials: MK
authors.lastname: Doyle
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004334:Drug Administration Schedule; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D007279:Injections, Subcutaneous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate
keywords: Anti-TNF; DAS28; Rheumatoid Arthritis
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