POS0079 DOES METHOTREXATE IMPACT USTEKINUMAB IMMUNOGENICITY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS? A POST HOC ANALYSIS OF SAMPLES FROM A RANDOMIZED, PLACEBO-CONTROLLED TRIAL.

Abstract

BackgroundThe formation of antidrug-antibodies (ADA) may reduce treatment efficacy or provoke discontinuation due to adverse reactions. Subsequent alterations in the drugs’ pharmacodynamics, pharmacokinetics, safety, and efficacy are often unpredictable and can impede clinical discourse. Recent studies gave us some insights regarding the role of ADA formation against the monoclonal IL-12/-23 antibody ustekinumab (UST) and the impact of concomitant MTX treatment on immunogenicity in psoriatic arthritis (PsA) patients [1,2]. Valid measurement of ADA, particularly of neutralizing ADA (nADA) is essential to understand UST-associated immunogenicity and may help to predict clinical outcomes.ObjectivesTo examine the impact of concomitant MTX on UST-immunogenicity in patients with active psoriatic arthritis (PsA).MethodsPlasma samples were collected from a randomized controlled trial in patients with active PsA, treated with open UST and placebo-controlled methotrexate over a 52 weeks. We compared samples of 112 patients treated with either UST and MTX (n=58) or UST and placebo (n=54). Plasma samples were obtained shortly before UST injection at weeks 0, 4, 16, 40, and 52.Immunogenicity testing was performed as described by our group elsewhere [3], in a multitiered manner with ELISA and surface plasmon resonance analysis for the detection and quantification of ADA and UST, respectively. Neutralizing capacity was characterized in a cell-based assay. For statistical analysis, a two-way ANOVA with Sidak correction for multiple comparisons was used.ResultsOver the 52 weeks treatment period, 10 (18 %) of patients in the placebo cohort developed UST-specific ADA with one patient having non-neutralizing ADA, whereas 15 (27 %) subjects in the MTX cohort generated UST-specific ADA with 2 patients having non-neutralizing ADA. The ADA rates and concentrations at the different time points (Figure 1A, B) did not differ significantly between MTX and non-MTX users (p< 0.05). Furthermore, the presence of UST-specific ADA was not associated with decreased UST levels (Figure 1C).Figure 1.(A) ADA prevalence (%), (B) mean concentration (µg/ml) of confirmed ADA with 95%confidence interval and (C) mean UST concentration (µg/ml) with 95%confidence intervall in the MTX cohort (UST/MTX; n=58) and placebo cohort (UST/pbo; n=54) overall and with confirmed ADA (ADA+), respectively, at week (w) 0, 4, 16, 40, and 52.ConclusionThe presented data yielded no statistically significant difference in ADA detection between the two analyzed groups. Our findings suggest that concomitant MTX had no impact on UST immunogenicity in PsA patients.References[1]McInnes, I. B. et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382(9894):780-9.[2]Leonardi, C.L. et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet, 371 (2008), pp. 1665-1674.[3]Mojtahed Poor, S. et al. Immunogenicity assay development and validation for biological therapy as exemplified by ustekinumab. Clin Exp Immunol. 2019;196(2):259-275.AcknowledgementsSorwe Mojtahed Poor received research support from the German Society of Rheumatology (DGRh e.V.)Disclosure of InterestsSorwe Mojtahed Poor: None declared, Marina Henke: None declared, Thomas Ulshoefer: None declared, Frank Behrens Grant/research support from: Janssen, Michaela Köhm Grant/research support from: Janssen, Harald Burkhardt: None declared, Susanne Schiffmann: None declared