Prediction of treatment response in psoriasis with measurement of serum levels of adalimumab, etanercept, and antidrug antibodies: a pilot study

Abstract

BackgroundA substantial proportion of patients with psoriasis do not respond or lose initial response to tumour necrosis factor antagonists. This may partly be attributable to development of an immunogenic antibody response which causes subtherapeutic drug levels because of the clearance of drug-antidrug complexes. The aim of this study was to investigate the association between serum drug (adalimumab and etanercept) levels, antidrug antibodies, and clinical response in a cohort of psoriasis patients. MethodsIn a single-centre cohort of 56 adults with psoriasis initiated on adalimumab or etanercept between 2009 and 2011, drug and antidrug antibody levels were measured with a commercially available ELISA at the patients’ routine clinic reviews (4, 12, and 24 weeks of treatment and the last available observation). Responders were defined as having a 75% reduction in psoriasis area and severity index from baseline (PASI 75) within 6 months of treatment, or physician's global score of clear or nearly clear. Non-responders were defined as not achieving a 50% reduction in PASI from baseline (PASI 50) within 6 months or having a loss of PASI 50 treatment response. FindingsAfter 4 weeks of therapy, adalimumab levels were significantly higher in responders than in non-responders (median 5·00 μg/mL [IQR 4·30–5·00] vs 0·12 μg/mL [0·10–1·79], p=0·003) and these higher levels were sustained at 12 and 24 weeks. Anti-adalimumab antibodies were detected in 25% of non-responders (2/8 patients, mean follow-up 22·5 weeks) and not in any responders (n=23, mean follow-up 26·1 weeks). There was no significant association between etanercept levels and clinical response at 4 weeks (median 2·94 μg/mL [IQR 0·78–3·68] vs 1·40 [0·82–2·12], p=0·317), and no anti-etanercept antibodies were detected. InterpretationAdalimumab drug level monitoring at 4 weeks may be useful in predicting treatment response, in contrast to etanercept drug levels. The majority of adalimumab non-responders did not have antidrug antibodies; however, lack of serum trough levels and assay limitations may have underestimated their prevalence. Larger studies are required to investigate other factors contributing to low drug levels and to assess the usefulness of these drug and antidrug assays in personalising therapy in psoriasis. FundingNational Institute for Health Research.