Session Title: Pediatric Rheumatology: Clinical and Therapeutic Disease IV: Childhood Therapeutics and Response
Session Type: Abstract Submissions (ACR)
Due to their proteinaceus character biologics can often induce an unwanted immune response that results in the formation of anti-drug antibodies in patients receiving biologic therapy. We therefore analyzed the sera of juvenile idiopathic arthritis patients receiving either infliximab (IFX), adalimumab (ADA) or etanercept (ETA) for the presence of anti-IFX, anti-ADA and anti-ETA antibodies.
We determined the serum drug levels and anti-drug antibody levels in the sera of 26 patients on IFX, 12 patients on ADA and 19 patients on ETA therapy. In the cases where we detected the presence of anti-drug antibodies we also investigated whether these antibodies bind the Fab or Fc fragments and compared laboratory findings with the clinical response to therapy.
We detected anti-drug antibodies in 11 out of 26 (42%) patients on IFX and 4 out of 12 (33%) patients on ADA therapy, but found no anti-ETA antibodies in any of the 19 patients treated with ETA. Anti-drug antibodies were in all cases associated with decreased serum drug levels, which in the majority of cases were below the limit of detection. For the two monoclonal antibody drugs (IFX and ADA) we observed that the anti-drug antibodies bound the Fab fragments, i.e. the regions responsible for TNF binding.
The level of immunogenicity for patients receiving biologic therapy closely followed the degree of foreignness of the biologic drugs, with IFX inducing the formation of anti-IFX antibodies in the highest proportion of patients, followed by ADA, while ETA did not induce the formation of anti-ETA antibodies in any of the patients included in our study. Once anti-drug antibodies had developed they were in all cases associated with decreased serum drug levels, however not all non-responders showed low serum drug levels or tested positive for anti-drug antibodies, indicating a different disease mechanism. Monitoring of serum drug levels and the detection of anti-drug antibodies may therefore be important for determining the best personalized treatment strategy and enabling a more cost effective treatment.
V. Curin Serbec,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-drug-antibodies-are-associated-with-diminished-drug-levels-and-treatment-failure/