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FRI0269 The Utility of the Mechanistic Model in Inflammatory Arthropaties with Secondary Clinical Failure to Adalimumab, but not to Etanercept
  1. S. Bandrés Ciga1,2,
  2. J. Salvatierra Ossorio1,
  3. M. Lόpez-Sidro3,
  4. A. García Sánchez3,
  5. R. Durán Ogalla2,
  6. F. Vives Montero2,
  7. E. Raya-Άlvarez1
  1. 1Rheumatology Division, University Hospital San Cecilio
  2. 2Physiology, University of Granada
  3. 3Rheumatology Division, University Hospital Virgen de las Nieves, Granada, Spain

Abstract

Background The development of biological therapies which block the tumor necrosis factor alfa (TNFα) has revolutionized the treatment of various inflammatory diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Nevertheless, approximately 35% of patients starting biological therapies against TNFα do not respond (primary clinical failure) [1] and it is estimated that approximately 30% of responders will present a clinical failure after having responded for at least 6 months (secondary clinical failure) [2]. Among the mechanisms responsible for the secondary clinical failure the importance of immunogenicity induced by these drugs has been suggested. Biological therapies may induce an unwanted immune response leading to the formation of antibodies against drugs (ADA). These ADA affect the bioavailability of the biological drug, frecuently leading to subtherapeutic levels and thereby causing a loss of clinical response.

Objectives To assess the concordance between secondary clinical failure (definition based on DAS28 or BASDAI) and the type of mechanistic failure (definition based on drug levels) in patients with inflammatory arthropaties.

Methods Immunogenicity was measured in patients with RA, AS and PsA who presented secondary clinical failure under treatment with ADL or ETN. Blood samples were collected immediately before drug administration (trough levels). Drug and ADA concentrations were determined in patient's serum by ELISA.

Results 23 patients with secondary clinical failure were recruited: 73.91% had RA, 8.69% PsA and 17.39% AS. 56.52% did not respond to ADL whilst 43.48% did not respond to ETN. None of the patients treated with ETN showed either subtherapeutic drugs levels or ADA (primary mechanistic failure), whereas it was found that 17.39% of the patients treated with ADL had subtherapeutic drug levels for reasons attributable to immunogenicity (secondary mechanistic failure; p=0.000048). No correlation was found among the type of mechanistic failure and the time of clinical efficacy (p=0.469), disease duration (p=0.39), treatment with previous biological therapies (p=0.15) and the concomitant treatment with corticosteroids (CS) (p=0.24) and disease-modifying antirheumatic drugs (DMARDs) (p=0.50).

Conclusions 1. The mechanistic model in patients with secondary clinical failure to ADL may present clinical utility. 2. Immunogenicity appears not to play a relevant role in the secondary clinical failure to ETN. 3. In clinical practice determining drug and ADA levels may only be useful in non-responders to ADL.

References

  1. Wiens A, Venson R, Correr CJ, Otuki MF, Pontarolo R.Meta-analysis of the efficacy and safety of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis. Pharmacotherapy 2010; 30:339-53.

  2. Remy A, Avonac J, Gossec L, Combe B. Clinical relevance of switching to a second tumour necrosis factor-alpha inhibitor after discontinuation of a first tumour necrosis factor-alpha inhibitor in rheumatoid arthritis: a systematic literature review and meta-analysis. Clin Exp Rheumatol 2011; 29:96-103.

Acknowledgements The authors would like to thank the patients who offered to participate in the study. We also thank Angela Tate for assistance with the English version and IG for his time and effort.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.2563

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