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CERTOLIZUMAB PEGOL IS EFFECTIVE IN THE TREATMENT OF CROHN'S DISEASE PATIENTS WITH OPEN FISTULAS
M Khaliq-Kareemi1, S Schreiber2, I Lawrance3, O Thomsen4, S Hanauer5, R Bloomfield6, W Sandborn7
1Alberta Health Services, Calgary, Alberta; 2Christian Albrechts University, Kiel, Germany; 3University of Western Australia, Freemantle, Western Australia; 4University of Copenhagen, Herlev, Denmark; 5University of Chicago Medical Center, Chicago, Illinois, USA; 6UCB Pharma, Slough, United Kingdom; 7Mayo Clinic, Rochester, Minnesota, USA
Aims: Exploration of certolizumab pegol (CZP) efficacy in the subpopulation of patients with fistulizing Crohn's disease (CD) who entered the Phase III maintenance study of CZP - PRECiSE 2.
Methods: All patients enrolled in PRECiSE 2 received open-label induction with CZP 400 mg at Wks 0, 2, and 4. Those who responded (reduction of =<100 points from baseline on the Crohn's Disease Activity Index [CDAI] at Wk 6) were randomized to CZP 400 mg or placebo every 4 wks with final assessment at Wk 26. Efficacy measures included CDAI response and remission (score of =<150 points) and assessment of health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). This subgroup analysis only included patients who had open fistulas at Wk 0. Fistula closure, ie, the absence of drainage on gentle compression, was defined: (a) during the study - closure of at least 50% of open fistulae at any 2 consecutive postbaseline visits at least 3 wks apart; (b) Wk 26 - 50%, a 50% minimum closure in the number of open fistula at Wk 26 compared to Wk 0; and (c) Wk 26 - 100%, 100% closure in the number of open fistulas at Wk 26 compared to Wk 0.
Results: Fifty-eight of the 425 patients (13.6%) who responded to CZP induction, had open fistulas at baseline: 30 were randomized to placebo and 28 to CZP 400 mg. During the study, 43.3% (n=13) of patients who had received CZP induction then placebo and 53.6% (n=15) of those on continuous CZP had fistula closure. Among patients who had fistula closure during the study, a higher proportion of those on continuous CZP maintained 50% fistula closure at Wk 26 vs placebo: 73.3% (n=11/15) vs 38.5% (n=5/13), respectively; and 100% fistula closure: 66.7% (n=10/15) vs 30.8% (n=4/13), respectively. In the subpopulation of patients with open fistula at baseline, a higher percentage in the CZP vs placebo group achieved CDAI-response-100 (71.4% vs 33.3%) and CDAI remission (53.6% vs 20.0%). For IBDQ, mean change scores from baseline to Wk 26 were greater (ie, better improvement) in the CZP- (36.7 points) than placebo-treated groups (20.7-points). There was a higher rate of discontinuation from treatment in the placebo group compared to CZP; 50% (n=15) and 14% (n=4), respectively.
Conclusions: This analysis suggests that CZP short-term induction therapy is efficacious in treating patients with fistulizing CD. Under maintenance therapy with stable dosing, fistula in most patients treated continuously with CZP stay closed. Patients with fistula closure have a low CDAI and a high quality of life.