Concomitant MTX May Not Affect Ustekinumab Levels, Antidrug Antibody Formation in PsA

In patients with psoriatic arthritis (PsA) receiving treatment with ustekinumab, concurrent use of methotrexate (MTX) did not appear to have an effect on antidrug antibody (ADA) formation, according to findings from a post hoc analysis published in Rheumatology (Oxford).

Ustekinumab-associated immunogenicity may include the formation of ADAs that can weaken the mode of action through alterations in pharmacokinetics and pharmacodynamics.

Investigators sought to identify patient-, disease-, and treatment-associated features that enhance the formation of ADAs, as well as to differentiate patient groups at an elevated risk for the development of immunogenicity with ustekinumab treatment. In addition, the effect of concomitant MTX treatment/pretreatment on ustekinumab immunogenicity was assessed among patients with PsA.

The post hoc analysis was derived from the phase 3, multicenter, randomized, placebo-controlled, double-blind MUST study (ClinicalTrials.gov Identifier: NCT03148860).

The investigators examined serum samples patients who received treatment with open-label ustekinumab and concurrent MTX (ustekinumab-plus-MTX cohort) or placebo (ustekinumab-plus-placebo cohort).

To establish the effect of ADA formation on ustekinumab efficacy and trough levels, patients were stratified based on week 52 Disease Activity in Psoriatic Arthritis (DAPSA) score. A DAPSA score of less than 4 was defined as “remission,” and a DAPSA score of greater than 4 or a Disease Activity Score in 28 joints (DAS28) score of 3.2 or lesser was considered as “active disease.”

During the 52-week study period, 19 of the 58 patients who received ustekinumab plus MTX and 11 of the 54 patients who received ustekinumab plus placebo developed ADAs (P >.05). Visit-dependent mean ustekinumab levels in the overall ustekinumab-plus-MTX group were 0.052 (±0.04) μg/mL to 0.106 (±0.07) μg/mL. In patients with confirmed ADA, the mean range of ustekinumab levels were 0.029 (±0.03) μg/mL to 0.097 (±0.07) μg/mL.

In addition, mean ustekinumab concentrations in the overall ustekinumab-plus-placebo group were 0.047 (±0.05) μg/mL to 0.119 (±0.07) μg/mL. In patients with confirmed ADA, the mean range of ustekinumab levels were 0.037 (±0.04) μg/mL to 0.091 (±0.08) μg/mL.

A significant linear relationship was observed between ustekinumab levels and detection of ADAs (P =.02). Further, at week 52, clinical and safety outcomes did not differ significantly between patients with ADA-positivity and -negativity (P >.05).

A key limitation of the current analysis was the small number of individuals who developed ADAs, which may have led to the misinterpretation of data.

Study authors concluded, “[W]e advise immunogenicity testing as a personalized approach to explore the underlying causes of drug-related adverse events and derive mitigation strategies from the findings obtained.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.