title: Immunogenicity, safety, and efficacy of abatacept administered subcutaneously with or without background methotrexate in patients with rheumatoid arthritis: results from a phase III, international, multicenter, parallel-arm, open-label study.
abstract: OBJECTIVE
  To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy.
  
  
  METHODS
  This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibody-positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20.
  
  
  RESULTS
  Ninety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were -1.67 (95% confidence interval [95% CI] -2.06, -1.28; combination) and -1.94 (95% CI -2.46, -1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were -1.84 (95% CI -2.23, -1.34; combination) and -2.86 (95% CI -3.46, -2.27; monotherapy) at month 18.
  
  
  CONCLUSIONS
  SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.
authors.affiliation: University of Queensland, Brisbane, Queensland, Australia. pnash@tpg.com.au
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.forename: Sauithree
authors.initials: S
authors.lastname: Nayiager
authors.forename: Mark C
authors.initials: MC
authors.lastname: Genovese
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kivitz
authors.forename: Kurt
authors.initials: K
authors.lastname: Oelke
authors.forename: Charles
authors.initials: C
authors.lastname: Ludivico
authors.forename: William
authors.initials: W
authors.lastname: Palmer
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez
authors.forename: Ingrid
authors.initials: I
authors.lastname: Delaet
authors.forename: Ayanbola
authors.initials: A
authors.lastname: Elegbe
authors.forename: Michael
authors.initials: M
authors.lastname: Corbo
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000276:immunology; D055261:Immunogenetic Phenomena / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007279:Injections, Subcutaneous; D038622:Internationality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000276:immunology; D008875:Middle Aged; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018796:Immunoconjugates; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept; D008727:Methotrexate