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

Abstract

Background: Dose escalation is often recommended for loss of response in anti-TNFα-treated patients with Crohn's disease (CD). This 52-week phase 3, multicenter study investigated the efficacy and safety of escalation to adalimumab 80 mg every other week (EOW) in Japanese patients with CD who lost response to maintenance adalimumab 40 mg EOW.

Methods: Twenty-eight patients aged ≥15 years with moderately to severely active CD who had previously attained and subsequently lost clinical response to maintenance ada limumab received open-label adalimumab 80 mg EOW during weeks 0-50. Loss of response was defined as CD activity index (CDAI) ≥200, increases in CDAI ≥50 from minimum observed value, and C-reactive protein (CRP) ≥1 mg/dL at screening. The primary endpoint was the proportion of patients achieving a CDAI decrease ≥50 (CR-50) from baseline at week 8.

Results: At weeks 8 and 52, 75.0 and 57.1$ of patients achieved CR-50 and 25.0 and 35.7$ achieved clinical remission (CDAI < 150), respectively; median CRP changes from baseline were -0.39 and -0.77 mg/dL, respectively. Most treatment-emergent adverse events were mild to moderate.

Conclusions: Adalimumab dose escalation to 80 mg EOW improved CD activity in patients who had lost response to maintenance adalimumab, with no new safety signals. (ClinicalTrials.gov Identifier: NCT01958827.).

Keywords: Clinical response; Clinical trials; Crohn disease; Dose escalation; Tumor necrosis factor.

Figures

Fig. 1

Proportion of patients with CR-50, CR-70, CR-100, and clinical remission from weeks 4 to 52 (NRI; n = 28). CR-50, decrease in CDAI ≥50; CR-70, decrease in CDAI ≥70; CR-100, decrease in CDAI ≥100. CDAI, Crohn's disease activity index; NRI, nonresponder imputation.

Fig. 2

Median change from baseline (a) and proportion of patients with ≥50$ drop in CRP over time (b) (LOCF; n = 28). CRP, C-reactive protein; LOCF, last observation carried forward.