Prospective Randomized Trial For Evaluation Of Hemostasis With Soft Coagulation For Bleeding Gastric Ulcers

BACKGROUND: Certolizumab pegol (CZP) is a PEGylated anti-TNF-α therapy that was effective at inducing fistula closure in a post-hoc analysis of the 26-week open-label induction and double-blind maintenance study in Crohn's disease (CD) (PRECiSE 2 [P2], NCT00152425).OBJECTIVE: We now report 3-year data for maintenance of response and remission in the subpopulation of P2 patients with fistulizing CD who continued to receive open-label CZP (PRECiSE 3 [P3] extension study, NCT00160524).METHODS: Patients enrolled in P2 received open-label induction at Weeks 0, 2, and 4 with subcutaneous CZP 400 mg.Responders (≥100-point reduction from baseline in CD Activity Index [CDAI] at Week 6) were randomized to CZP 400 mg or placebo q4w and assessed at Week 26.Patients who completed P2 and entered P3 received open-label CZP 400 mg q4w.In P3, efficacy measures included Harvey-Bradshaw Index (HBI) response (≥3-point decrease from baseline) and remission (HBI ≤4).This analysis only included patients who had open fistulas at Week 0 of P2.Fistula closure was defined as the absence of drainage on gentle compression in ≥50% of open fistulae at any 2 consecutive post-baseline visits at ≥3 weeks apart during the study.RESULTS: 58 patients in the intention-to-treat population of P2 who responded to CZP induction (13.6% of 425) had open fistulas at baseline: 30 were randomized to placebo and 28 to CZP 400 mg.Of these, 35 patients entered P3 (placebo n=14 and CZP 400 mg n=21 from P2). Fistula closure was observed in 52.4% (11/21) of patients assigned to CZP 400 mg compared with 42.9% (6/14) on placebo in P2.Of those in the active group in P2, response and remission rates were higher in patients with fistula closure than in patients with open fistula, and were maintained through to Week 154 of P3 (Table ).CONCLUSIONS: Carry-over from open-label induction led to some fistula response under placebo during the maintenance phase of P2.Most former placebo patients had closed fistula after switching to open-label CZP 400 mg q4w.Long-term maintenance with CZP 400 mg q4w was efficacious at maintaining clinical response and remission in patients with fistulizing CD.