title: Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis.
abstract: BACKGROUND
  A substantial proportion of patients with rheumatoid arthritis (RA) do not respond, or lose initial response, to adalimumab treatment. One explanation for non-response is that patients develop anti-adalimumab antibodies.
  
  
  OBJECTIVE
  To evaluate the incidence of formation of antibody against adalimumab and the association with serum adalimumab concentrations and clinical response.
  
  
  METHODS
  In a cohort of 121 consecutive patients with RA treated with adalimumab, serum adalimumab concentrations and antibodies against adalimumab were measured together with clinical response variables before and up to 28 weeks after the start of treatment.
  
  
  RESULTS
  Anti-adalimumab antibodies were detected in 21 patients (17%) during 28 weeks of treatment. EULAR non-responders had antibodies significantly more often than good responders (34% vs 5%; p = 0.032). Patients with antibodies showed less improvement in disease activity (mean (SD) delta DAS28 0.65 (1.35)) than patients without antibodies (mean delta DAS28 1.70 (1.35)) (p = 0.001). Patients with antibodies during follow-up had lower serum adalimumab concentrations at 28 weeks than patients without antibodies (median 1.2 mg/l, range 0.0-5.6 vs median 11.0 mg/l, range 2.0-33.0, respectively; p<0.001). Good responders had higher serum adalimumab concentrations than moderate responders (p = 0.021) and non-responders (p = 0.001). Concomitant methotrexate use was lower in the group with anti-adalimumab antibodies (52%) than in the group without antibodies (84%) (p = 0.003).
  
  
  CONCLUSIONS
  Serum antibodies against adalimumab are associated with lower serum adalimumab concentrations and non-response to adalimumab treatment.
authors.affiliation: Jan van Breemen Institute, 1056 AB Amsterdam, The Netherlands.
authors.forename: Geertje M
authors.initials: GM
authors.lastname: Bartelds
authors.forename: Carla A
authors.initials: CA
authors.lastname: Wijbrandts
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: Steven
authors.initials: S
authors.lastname: Stapel
authors.forename: Willem F
authors.initials: WF
authors.lastname: Lems
authors.forename: Lucien
authors.initials: L
authors.lastname: Aarden
authors.forename: Ben A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: Paul Peter
authors.initials: PP
authors.lastname: Tak
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Wolbink
mesh_terms: D000068879:Adalimumab; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000276:immunology / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate