Biologic therapies have transformed treatment of immune-mediated inflammatory diseases, yet significant numbers of patients experience treatment failure. Variability in drug levels correlate with outcomes across multiple inflammatory diseases, but with limited data in psoriasis. In this prospective observational cohort study (n=60 dermatology specialist centres), we determine the clinical utility of therapeutic drug monitoring using the exemplar TNF antagonist adalimumab. Adults (n=515) recruited to Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) within the biologics pharmacovigilance British Association of Dermatologists Biologic Interventions Registry (BADBIR) with serial adalimumab level measurements up to one year were included (n=888 samples; 63% male; average age 44 years (sd 12). Response to treatment at 6 months was defined as PASI 75 (primary outcome).  We found that drug level can discriminate responders from non-responders with a minimally effective adalimumab level identified as 3.3 µg/ml (sensitivity: 80%, specificity: 57%, Area Under Curve: 0.73 (95% CI: 0.67-0.79)). Multilevel mixed effect logistic regression modelling to account for clustering of samples within patients, as well as adjusting for covariates, indicates that a target drug level of 7 µg/ml will achieve a minimum 80% probability of response (81%; 95% CI: 76-86%).  Early serum drug level was confirmed as an additional independent indicator of 6-month PASI 75 response (OR(sqrt drug level) 1.95, 95%CI 1.06-3.57, p=0.031) and PASI 90 response (OR(sqrt drug level) 2.38, 95% CI 1.26-4.50; p=0.008), substantially improving model goodness of fit. Smoking and disease duration were also key baseline predictors influencing interindividual variation. This real-world study with pragmatic drug level sampling provides strong evidence to support proactive measurement of drug levels in the management of psoriasis, and highlights the importance of taking drug levels into account when searching for biomarkers of treatment response.

Developing a therapeutic range and predicting response to biologics in patients with psoriasis: a multicentre prospective observational cohort study