title: Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival.
abstract: OBJECTIVE
  To compare effectiveness, drug survival, and safety between infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid arthritis (RA) patients.
  
  
  METHODS
  This study is a prospective cohort study of 1208 active RA patients. Effectiveness, drug survival, and serious adverse events during entire follow-up (median 2.9 years) were monitored.
  
  
  RESULTS
  EULAR and CDAI responses were comparable between the three agents (EULAR good/moderate responses at 12 months ranged 76-79%). At 12 months, 15-23% achieved remission. For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7-4.1 and 1.3-3.4, respectively); males (HR 1.6; 1.1-2.4), use of glucocorticoids (HR 2.0; 1.3-3.0), and swollen joint count >7 (HR 0.36; 0.24-0.55) were independent predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab, adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated with significantly more withdrawals due to adverse events. Disease activity, CRP, and use of glucocorticoids predicted efficacy-related drug survival; age, use of methotrexate, and prior DMARDs failures predicted safety-related survival. Risk for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38-1.00) or etanercept (OR 0.39; 0.21-0.72) than infliximab, independent of the effects of age (OR 1.65; 1.37-2.00 per 10 years), tender joint count >10 (OR 1.86; 1.21-2.86), and glucocorticoids >35mg/week (OR 1.83; 1.12-2.99).
  
  
  CONCLUSIONS
  Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed.
authors.affiliation: Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Voutes, 71003 Heraklion, Greece.
authors.forename: Irini
authors.initials: I
authors.lastname: Flouri
authors.affiliation: Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Theodora E
authors.initials: TE
authors.lastname: Markatseli
authors.affiliation: Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Paraskevi V
authors.initials: PV
authors.lastname: Voulgari
authors.affiliation: Rheumatology Department, Sismanoglio Hospital, Athens, Greece.
authors.forename: Kyriaki A
authors.initials: KA
authors.lastname: Boki
authors.affiliation: Rheumatology Clinic, General Hospital of Kavala, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papadopoulos
authors.affiliation: First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School, Thessaloniki, Greece.
authors.forename: Loukas
authors.initials: L
authors.lastname: Settas
authors.affiliation: First Department of Internal Medicine, Rheumatology Section, AHEPA Hospital of the Aristotle University Medical School, Thessaloniki, Greece; Department of Rheumatology, 424 General Army Hospital, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zisopoulos
authors.affiliation: Department of Nutrition and Diebetics, Harokopio University, Athens, Greece.
authors.forename: Fotini N
authors.initials: FN
authors.lastname: Skopouli
authors.affiliation: Department of Rheumatology, Veterans Administration Hospital, Athens, Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Iliopoulos
authors.affiliation: Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Voutes, 71003 Heraklion, Greece.
authors.forename: George K
authors.initials: GK
authors.lastname: Bertsias
authors.affiliation: Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Pierre
authors.initials: P
authors.lastname: Geborek
authors.affiliation: Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Alexandros A
authors.initials: AA
authors.lastname: Drosos
authors.affiliation: Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Voutes, 71003 Heraklion, Greece; Faculty of Medicine, National and Kapodestrian University of Athens, Athens, Greece.
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Boumpas
authors.affiliation: Rheumatology, Clinical Immunology and Allergy, Medical School, University of Crete, Voutes, 71003 Heraklion, Greece. Electronic address: sidiropp@med.uoc.gr.
authors.forename: Prodromos
authors.initials: P
authors.lastname: Sidiropoulos
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012042:Registries; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: Arthritis; Biological therapies; Efficacy; Glucocorticoids; Infections; Registry; Safety