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FRI0707 Drug levels and antidrug antibodies in the development of paradoxical psoriasis and palmoplantar pustulosis

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Background The pathogenesis of psoriasis and palmoplantar pustulosis induced by Tumor Necrosis Factor inhibitors (TNFi) is largely unknown. Only one study, in 9 inflammatory bowel disease patients, investigated the relation… Click to show full abstract

Background The pathogenesis of psoriasis and palmoplantar pustulosis induced by Tumor Necrosis Factor inhibitors (TNFi) is largely unknown. Only one study, in 9 inflammatory bowel disease patients, investigated the relation with infliximab drug levels in the development of psoriasis or palmoplantar pustulosis and demonstrated no relation with of trough concentrations in these events (1). However, psoriasis and palmoplantar pustulosis were not studied separately. Objectives To study the differences in drug levels and antidrug antibodies (ADA) of TNFi in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients who developed de novo psoriasis, palmoplantar pustulosis and those who did not develop skin adverse events. Methods In this retrospective study data was collected from the observational cohorts of Reade of consecutive RA and AS patients in whom TNFi was started. At every visit, serum samples were collected. We quantified the samples before/on time of event of the patients who developed psoriasis or palmoplantar pustulosis, for the patients with no skin adverse events (control group) at 24 or 28 weeks. Drug levels and ADA were measured with an Enzyme-linked immunosorbent assay and antibody binding test respectively. Results A total of 830 TNFi naive patients with RA and AS were included, of whom 21 developed psoriasis (n=11) or palmoplantar pustulosis (n=10). These patients were only observed in the adalimumab and etanercept cohorts. Sixteen patients with an event and 585 patients in the control group had serum samples available to quantify drug levels and ADA. No statistical significant differences were found in drug levels of adalimumab and etanercept for both RA and AS patients (table 1). Moreover, no statistical significant differences were observed in the detection of ADA between the three groups. However, no ADA were detected in patients who developed psoriasis or palmoplantar pustulosis compared to the overall 13.9% of the RA patients and 25.5% in AS patients.Table 1. Differences in drug levels and detection of anti-drug antibodies between palmoplantar pustulosis, psoriasis and control group Drug levels adalimumab Drug levels etanercept Anti-drug antibodies adalimumab, (μg/ml; median (IQR) (μg/ml); median (IQR) no. (%) RA  Palmoplantar pustulosis n=3 7,6 (0,01–12,0) n=1 4,4 n=3 0 (0)  Psoriasis n=3 8,5 (6,5–10,0) n=2 2,3 (1,5–3,1) n=2 0 (0)  Control group n=153 7,4 (4,0–10,0) n=89 2.7 (1.9–3.9) n=151 21 (13,9)  p-value 0,992 0,380 0,674 AS  Palmoplantar pustulosis n=3 9,0 (6,5–10,0) n=1 1,7 n=3 0 (0)  Psoriasis n=1 10, 0 n=2 1,3 (0,8–1,7) n=1 0 (0)  Control group n=46 8,5 (3,7–11,3) n=99 2.6 (1.4–4.0) n=47 12 (25,5)  p-value 0,754 0,406 0,754 RA: rheumatoid arthritis; AS: ankylosing spondylitis; Control group: patients who did not develop skin adverse events; IQR: interquartile range; no. number of patients. p-value <0,05 was considered statistically significant. Conclusions Patients who develop paradoxical psoriasis and palmoplantar pustulosis have adequate drug levels and no ADA were detected. References J Crohns Colitis 2015 Nov;9(11):982–7. Disclosure of Interest None declared

Keywords: drug; psoriasis; drug levels; palmoplantar pustulosis

Journal Title: Annals of the Rheumatic Diseases
Year Published: 2017

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