FRI0109 Drug immunogenicity and the development of paradoxical adverse events with biologic therapies

Autor: Rodica Chirieac, G. Strugariu, R. Paiu, Codrina Ancuta, L. Petrariu, E. Ancuta, Cristina Pomirleanu, A. Chiriac
Rok vydání: 2018
Předmět:
Zdroj: FRIDAY, 15 JUNE 2018.
DOI: 10.1136/annrheumdis-2018-eular.4854
Popis: Background Defined as de novo or exacerbation of pathologies that usually responds to biologic agents, paradoxical reactions encompass for a wide spectrum of manifestations (cutaneous, intestinal, ocular) reported during biological therapy (TNF and non-TNF medications) regardless of the underlying rheumatic or non-rheumatic disorder. Objectives To assess drug levels (DL) and anti-drug antibodies (ADA) in patients with paradoxical reactions (de novo or exacerbation of psoriasis, uveitis, Crohn’s disease) induced by biological drugs (bDMARS) in Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Methods We performed a retrospective observational study in cohorts of consecutive RA (267), PSA (65) and AS (145) undergoing TNF (i-TNF) or non-TNF biologics according to the local recommendations for initiation and monitoring, attending a single academic rheumatology department. All patients were assessed at every 24 weeks months for disease activity and outcomes; supplementary, drug immunogenicity (ADA and DL) was systematically evaluated in patients developing paradoxical adverse events. DL and ADA were measured with an ELISA assay and antibody binding test, respectively. Serum drug levels were considered positive for infliximab if >0.035 µg/mL, for adalimumab >0.024 µg/mL, for etanercept >0.035 µg/mL, rituximab >0.75 µg/mL, while the cut-offs for ADA positivity to infliximab was established at 5AU/ml, for adalimumab at 10AU/mL, etanercept at 142 AU/mL, rituximab 140 AU/mL (ELISA, Progenika) Results 42 patients with paradoxical psoriasis (30 with de novo lesions, 18 with palmo-plantar pustulosis, 12 with exacerbation of pre-existent lesions), 12 with paradoxical uveitis (5 with a new onset uveitis) and 3 with paradoxical Crohn’s were included in the final analysis. Paradoxical events related to abatacept, certolizumab (one de novo psoriasis per agent) or golimumab (2 new onset uveitis, one flare of Chron’s disease) were excluded from the final analysis as no immunogenicity lab tests were provided. Drug induced paradoxical events were described not only with all TNF inhibitors but also with rituximab. DL was in normal range in all these patients; in addition, ADA were either negative, or, if present, had no impact on drug concentration. Furthermore, we found no significant differences in drug levels of TNF inhibitors for RA, PsA and AS. Moreover, no statistical significant differences were observed in the detection of ADA between the three groups. Conclusions Patients who develop either true or borderline paradoxical AE have adequate drug levels, with normal ADA concentrations. Disclosure of Interest None declared
Databáze: OpenAIRE
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