Clinical impact of antibodies against ustekinumab in psoriasis: an observational, cross-sectional, multicenter study.

Abstract Ustekinumab is an effective treatment for psoriasis, but response varies between patients. Formation of anti-drug antibodies (ADA) may explain part of this variation by reducing the free ustekinumab level. Currently published analyses of the clinical impact of ADA are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADA on ustekinumab level and clinical response as assessed by the Psoriasis Area and Severity Index (PASI). Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay (RIA) and a drug-tolerant ELISA (dtELISA). Circulating ustekinumab levels were measured using an ELISA. ADA were detected in 3.8% (95%CI 3.2-4.2) and in 10.6% (95%CI 7.9-13.9) of patients using the RIA and dtELISA, respectively. At least 85% of ADA were neutralizing. Compared to ADA-negative patients, ADA positivity in the RIA and dtELISA were associated with lower median ustekinumab levels (-0.62 μg/mL [95%CI -1.190 to -0.30] and -0.74 μg/mL [95%CI -1.09 to -0.47], respectively) and higher absolute PASI (+6.6 [95%CI 3.0-9.9] and +1.9 [95%CI 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA-status correlated with poor clinical outcome (median sample PASI 10.1, +6.5 [95%CI 3.9-8.8] compared to ustekinumab-positive patients). In conclusion, substantially reduced drug exposure resulting from ADA formation is associated with impaired clinical response.