Dose Escalation of Adalimumab Can Overcome Loss of Response in CD

In many regulatory territories, patients with Crohn disease (CD) who lose response to adalimumab at a dose of 40 mg given every other week may be given an escalation to 40 mg every week. However, in Japan, where adalimumab is typically administered by a healthcare provider rather than by the patient, a study investigated the efficacy, safety, and pharmacokinetics (PK) of adalimumab after a dose escalation to 80 mg every other week as a means to reduce the need for additional patient appointments.

The phase 3, multicenter, open-label, single-arm, 52-week study enrolled 28 patients, 25 of whom completed week 8, and 18 of whom completed week 52. All patients in the primary efficacy population were taking at least 1 concomitant medication during the study, including immunosuppressants, corticosteroids, and aminosalicylate.

At week 8, the proportion of patients who achieved a 50-point reduction in the Crohn Disease Activity Index (CR50) was 75.0%. The proportion of patients achieving CR50 was maintained from 67.9% at week 4 through 57.1% at week 52.

C-reactive protein (CRP) levels also decreased throughout the study period. The median change from baseline in CRP at week 8 was −0.390 mg/dL (range: −5.56 to 2.99). The proportion of patients with a 50% or greater reduction in CRP from baseline grew from 21.4% at week 4 to 46.4% at week 16, then remained steady through week 52.

In the PK assessment, the mean concentration of adalimumab at week 52 was 11.7 (±5.31) μg/mL in the 10 patients who achieved remission and 6.68 (±4.11 μg/mL) in the 8 patients who did not. One patient became positive for anti-drug antibodies during the study period.

A total of 24 patients reported at least 1 adverse event (AE), with nasopharyngitis being the most commonly reported AE. Four patients discontinued the study due to AEs.

The authors concluded that, in this patient population, dose escalation of adalimumab to 80 mg every other week was able to restore and maintain response through week 52, and no new safety concerns were identified with this dosing strategy.

Reference

Motoya S, Watanabe M, Wallace K, et al. Efficacy and safety of dose escalation to adalimumab 80 mg every other week in Japanese patients with Crohn’s disease who lost response to maintenance therapy. Inflam Intest Dis. 2018;2(4):228-235. doi: 10.1159/000486786.