Immunogenicity may not increase after tapering from adalimumab, etanercept, and ustekinumab a short report published in the Journal of Dermatological Treatment indicates.

This was a pharmacologic substudy of the multicenter, randomized CONDOR trial conducted at 6 sites in the Netherlands from  2016 to 2018. Patients (N=118) with psoriasis who had low disease activity and were treated with adalimumab (n=52), etanercept (n=28), and ustekinumab (n=38) were randomly assigned in a 1:1 ratio to receive dose reduction or usual care. Dose reduction was defined as a 67% reduction of the original dose achieved by interval prolongation and after 3 months, a decrease to 50%. For adalimumab, the reduced dosing occurred every 21 and 28 days, for etanercept every 10 and 14 days, and for ustekinumab every 18 and 24 weeks. Trough levels were evaluated from serum samples collected every 3 months.

Median baseline trough levels were 5.48 mg/mL, 1.39 mg/mL, and 0.54 mg/mL for the adalimumab, etanercept, and ustekinumab recipients, respectively. In a mixed model, the investigators observed that for all 3 treatments, trough levels decreased with greater dose reduction.


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Conversion to detectable anti-drug antibody (ADA) levels were observed in 1 of the dose reduction and 2 of the usual care recipients. No ustekinumab recipients developed ADAs.

Successful dose tampering was associated with disease duration, drug, baseline Psoriasis Area and Severity Index (PASI) score, and age at study inclusion (all P <.2). No variables were significant independent predictors of dose reduction success in the multivariate analysis.

This study may have been limited by not having earlier trough assessment for the patients receiving ustekinumab, as this therapy has a longer half-life than the other therapies and the observed levels may not represent exposure at earlier time points.

The study authors concluded, “Although groups are small, we did not find any alarming sign of increased immunogenicity, which may indicate that immunogenicity does not increase by interval prolongation in a stable low-disease activity cohort. […] This study provides important and reassuring insights into the pharmacological changes after dose tapering of adalimumab, etanercept, and ustekinumab.”

Reference

Atalay S, Berends SE, Groenewoud HMM, et al. Serum drug levels and anti-drug antibodies in the context of dose tapering by interval prolongation of adalimumab, etanercept and ustekinumab in psoriasis patients: results of the CONDOR trial.J Dermatolog Treat. 2022;1-5. doi:10.1080/09546634.2022.2043546