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SAT0391 A Diminished Clinical Response at 28 and 52 Weeks of Adalimumab Treatment in Patients with Psoriatic Arthritis is Associated with Anti-Drug Antibodies
  1. E. Vogelzang1,
  2. E. Kneepkens1,
  3. M. Nurmohamed1,
  4. A. van Kuijk1,
  5. T. Rispens2,
  6. G. Wolbink1,2,
  7. C. Krieckaert1
  1. 1Jan van Breemen Research Institute | Reade
  2. 2Sanquin, Amsterdam, Netherlands

Abstract

Background Immunogenicity, the formation of anti-drug antibodies (ADA), has important clinical implications for the treatment with adalimumab of patients with rheumatic diseases, since ADA are associated with lower effective drug levels, resulting in an absent or diminished response in some patients. In contrast to rheumatoid arthritis research on immunogenicity and clinical response in patients with psoriatic arthritis (PsA) is scarce.

Objectives To investigate the relationship between ADA, adalimumab drug levels and clinical response in a large, long-term follow-up cohort of patients with PsA during 52 weeks of follow-up.

Methods This prospective cohort study included 103 consecutive patients diagnosed with PsA and treated with 40 mg adalimumab subcutaneously every other week. Disease activity score in 28 joints (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and psoriasis area and severity index (PASI) were assessed at baseline and after 4, 16, 28, 40 and 52 weeks of treatment. Adalimumab concentrations and ADA were measured in serum trough samples, using an enzyme linked immunosorbent assay (ELISA) and a radio immunoassay (RIA), respectively.

Results After 52 weeks of treatment, 23 (22%) patients had detectable ADA. Serum adalimumab concentrations were significantly lower at 28 and 52 weeks in patients with detectable ADA compared to patients without detectable ADA (at week 28: 1.3 mg/L [IQR 0.0-3.2] vs 8.7 mg/L [IQR 5.7-11.5], p<0.0001; at week 52: 0.9 mg/L [IQR 0.0-2.9] vs 9.4 mg/L [IQR 5.7-12.1], p=0.0001). DAS28 at 28 weeks (2.16 vs 2.95, p=0.023) and 52 weeks (2.19 vs 2.95, p=0.024) showed a significant difference; patients with detectable ADA had a poorer clinical outcome than patients without (see Table 1).

Conclusions ADA was detected in 22% of the adalimumab treated PsA patients during 52 weeks of follow-up. These patients had lower adalimumab serum concentrations and a significantly poorer clinical outcome for DAS28 and CRP at week 28 and 52 compared to patients in whom ADA were not detected.

Disclosure of Interest E. Vogelzang: None declared, E. Kneepkens: None declared, M. Nurmohamed: None declared, A. van Kuijk: None declared, T. Rispens Speakers bureau: Pfizer and Abbvie, G. Wolbink Grant/research support: Pfizer, Speakers bureau: Pfizer and Amgen, C. Krieckaert Speakers bureau: Pfizer and Abbvie

DOI 10.1136/annrheumdis-2014-eular.2162

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