Briakinumab for treatment of Crohn's disease: results of a randomized trial

Abstract

Background: This study assessed the efficacy and safety of briakinumab, a human anti-IL-12/23p40 monoclonal antibody, compared with placebo for the induction and maintenance of remission in patients with moderately to severely active Crohn's disease.

Methods: In this phase 2b, multicenter, double-blind, parallel group study, 246 patients stratified by prior tumor necrosis factor-antagonist use and response, were randomized (1:1:1:3) to 4 intravenous induction regimens: placebo, 200, 400, or 700 mg briakinumab, at weeks 0/4/8. At week 12, responders in the placebo or 400-mg induction groups entered the maintenance phase with the same regimen, whereas responders in the 700-mg induction group were rerandomized (1:1:1) to receive placebo, 200, or 700 mg briakinumab at weeks 12/16/20. At week 24, patients in remission stopped receiving study drug (withdrawal phase) until relapse. Patients experiencing relapse, nonresponders, and nonremitters could enter the open-label phase.

Results: The primary end point of clinical remission at week 6 was not met. There were numerically greater rates of remission and response at 6, 12, or 24 weeks in patients treated with briakinumab. The safety and tolerability profile of briakinumab was similar in the induction and maintenance phases of the trial.

Conclusions: Briakinumab showed a similar safety and tolerability profile to placebo in the induction and maintenance phases, and comparable rates of serious adverse events, adverse events leading to discontinuation, and malignancy. These data provide support for the potential efficacy of briakinumab and other IL-12/23 inhibitors in the treatment of moderate-to-severe Crohn's disease.

FIGURE 1

Study design. Patients were randomized to 4 induction groups: placebo, 200, 400, or 700 mg briakinumab. The primary end point was clinical remission at 6 weeks. At week 12, clinical response was assessed and patients in the placebo and 400 mg induction group continued into the maintenance phase on the same regimen, whereas responders in the 700-mg induction group were rerandomized to receive placebo, 200, and 700 mg briakinumab. At week 24, patients in clinical remission stopped receiving the study drug (withdrawal phase) until relapse. Patients with relapse, nonresponse, or nonremission could enter the OL phase.

FIGURE 2

Patient disposition during entire study. AE, adverse event; MP, maintenance phase; WP, withdrawal phase.

FIGURE 3

Efficacy of briakinumab during the induction phase. A, Rates of clinical remission at weeks 6 and 12. Clinical remission was defined as CDAI score <150 points (*statistically significant versus placebo at P <0.05). B, Rates of clinical response at weeks 6 and 12 (defined as a decrease in CDAI score ≥100 points compared with week 0; *statistically significant versus placebo at P <0.05). C, Rates of clinical remission at week 6, stratified by baseline CRP levels (CRP ≥1 mg/dL or CRP <1 mg/dL). D, Rates of clinical remission at week 6, stratified by baseline history of anti-TNF treatment N.S., not statistically significant versus placebo at P <0.05.

FIGURE 4

Efficacy of briakinumab during the maintenance phase. A, Rates of clinical remission at week 24 (defined as CDAI score <150 points). B, Rates of clinical response at week 24 (defined as a decrease in CDAI score ≥100 points compared with week 0). C, Relapse rate at week 24 (defined as a CDAI increase ≥70 points compared with week 24 score and a minimum score of ≥220 points). BRI, briakinumab; N.S., not statistically significant versus placebo at P <0.05.