Crohn's disease: certolizumab, adalimumab demonstrate efficacy in prior users of infliximab

Certolizumab and adalimumab demonstrated efficacy in inducing and maintaining response in patients with Crohn's disease who have lost response or are intolerant to infliximab, reported researchers at the American College of Gastroenterology (ACG) Annual Scientific Meeting in Las Vegas, Nev.

A post hoc analysis of the PRECiSE 2 (Pegylated Antibody Fragment Evaluation in Crohn's Disease Safety and Efficacy) study demonstrated efficacy of certolizumab in patients with moderate-to-severe Crohn's disease whether or not they previously had taken infliximab.

PRECiSE 2 was a phase 3 study that included patients who responded at Week 6 to open-label induction therapy with certolizumab. The 425 participants were randomized to either placebo or certolizumab and followed for 26 weeks. Response rates at Week 26 were 62.8% of patients randomized to certolizumab versus 36.2% of patients randomized to placebo (P<.001). A clinical response in this study was defined as ≥100-point decrease in the Crohn's Disease Activity Index (CDAI). Almost half (47.9%) of certolizumab-treated patients were in clinical remission at Week 26 versus 28.6% of patients who received placebo (P<.001), with remission defined as a decrease in the CDAI of ≥150 points.

"Infliximab may be associated with infusion reactions and/or loss of clinical response," Dr Hanauer said, in noting the importance of studying alternative agents in prior users of infliximab.

Among infliximab-naïve patients, the rates of remission at Week 26 were 52.8% and 33.3% with certolizumab and placebo, respectively (P<.001), and among those with prior infliximab exposure, the rates of remission were 32.7% with certolizumab and 13.7% with placebo (P=.008).

In another analysis of PRECiSE 2 presented at the ACG meeting, certolizumab was associated with improvements in work-related outcomes, health-related quality of life, and overall health status compared with placebo, said Brian Feagan, MD, professor of medicine and epidemiology and biostatistics, University of Western Ontario, Canada.

All 4 dimensions of the Work Productivity and Activity Impairment questionnaire were improved significantly in patients assigned to certolizumab compared with those assigned to placebo. Certolizumab recipients missed 9.9% less work (P=.03) and had 15.4% less impairment while working (P<.001), 14.2% less overall work impairment (P=.004), and 9.1% less activity impairment (P=.004).

The proportion of patients who had ≥16-point improvement in the Inflammatory Bowel Disease Questionnaire, which defines response, was significantly greater with certolizumab compared with placebo (P<.001).

Overall health status as measured by the 36-Item Short-Form Health Survey (SF-36) and the EuroQol-5 Dimensions (EQ-5D) questionnaire also was significantly superior with certolizumab. Specifically, compared with placebo, the overall mental (P=.001) and physical (P=.014) component summaries of the SF-36 were significantly higher in certolizumab recipients. The Visual Analog Scale of the EQ-5D also was maintained at a significantly higher level with certolizumab (P=.002).

In the GAIN (Gauging Adalimumab Effectiveness in Infliximab Non-responders) study, also presented at the ACG meeting, 3 times as many patients with moderately to severely active Crohn's disease who had lost response to or were intolerant to infliximab achieved clinical remission with adalimumab versus placebo, Dr Hanauer stated.

GAIN was a randomized, double-blind study of 325 patients who lost response to or were intolerant to infliximab. Patients were randomized to either adalimumab 160 mg followed by 80 mg at Week 2 or placebo.

Approximately 60% of randomized patients had experienced prior adverse events when treated with infliximab; approximately 65% of these patients had acute reactions, and approximately 30% had delayed reactions. Approximately half of the patients in the study had lost response to infliximab.

At Week 4, 21% of adalimumab-treated patients achieved clinical remission compared with 7% of patients who received placebo (P≤.001). The clinical response rates also were significantly superior with adalimumab at Week 4 versus placebo.