title: Venous and arterial thromboembolic events in adalimumab-treated patients with antiadalimumab antibodies: a case series and cohort study.
abstract: OBJECTIVE
  We observed 3 patients who developed severe venous and arterial thromboembolic events during treatment with adalimumab, 2 of whom had rheumatoid arthritis (RA) and 1 of whom had psoriatic arthritis. Antiadalimumab antibodies were detected in all 3 patients. We undertook this study to determine whether the development of antiadalimumab antibodies was associated with thromboembolic events during adalimumab treatment.
  
  
  METHODS
  A retrospective search (with blinding with regard to antiadalimumab antibody status) for thromboembolic events was performed in a prospective cohort of 272 consecutively included adalimumab-treated RA patients. Incidence rates were calculated and hazard ratios (HRs) were estimated using Cox regression. None of the index patients were part of the cohort.
  
  
  RESULTS
  Antiadalimumab antibodies were detected in 76 of 272 patients (28%). Eight thromboembolic events were found, 4 of which had occurred in patients with antiadalimumab antibodies. The incidence rate was 26.9/1,000 person-years for patients with antiadalimumab antibodies and 8.4/1,000 person-years for patients without those antibodies (HR 3.8 [95% confidence interval 0.9-15.3], P = 0.064). After adjustment for duration of followup, age, body mass index, erythrocyte sedimentation rate, and prior thromboembolic events, the HR was 7.6 (95% confidence interval 1.3-45.1) (P = 0.025).
  
  
  CONCLUSIONS
  These findings suggest that the occurrence of venous and arterial thromboembolic events during adalimumab treatment is higher in patients with antiadalimumab antibodies than in those without antiadalimumab antibodies. Patient numbers were relatively small; therefore, validation in other cohorts is mandatory.
authors: VU University Medical Center, Amsterdam, The Netherlands.
authors: L A
authors: LA
authors: Korswagen
authors: G M
authors: GM
authors: Bartelds
authors: C L M
authors: CL
authors: Krieckaert
authors: F
authors: F
authors: Turkstra
authors: M T
authors: MT
authors: Nurmohamed
authors: D
authors: D
authors: van Schaardenburg
authors: C A
authors: CA
authors: Wijbrandts
authors: P P
authors: PP
authors: Tak
authors: W F
authors: WF
authors: Lems
authors: B A C
authors: BA
authors: Dijkmans
authors: R M
authors: RM
authors: van Vugt
authors: G J
authors: GJ
authors: Wolbink
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000453:epidemiology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab