Efficacy and tolerability of certolizumab pegol are sustained over 18 months: data from PRECiSE 2 and its extension studies (PRECiSE 3 and 4)

Abstract

PRECiSE 2, a 26-week, open-label induction, double-blind maintenance trial, demonstrated that certolizumab pegol — an Fc-free PEGylated Fab' anti-TNF— is effective and well-tolerated in active Crohn's disease (CD).1 Patients could enter openlabel extension studies evaluating long-term continued maintenance of response (PRECiSE 3) or re-induction and maintenance after relapse (PRECiSE 4). PRECiSE 3 and PRECiSE 4 are ongoing studies; results after 12 and 18 months' treatment are presented here. In PRECiSE 2, responders to open-label induction (Weeks 0, 2, 4) with certolizumab pegol 400 mg (64.1%) were randomized at Week 6 to certolizumab pegol 400 mg (n =215) or placebo (n=210) every 4 weeks (Week 8-24). Patients completing PRECiSE 2 could enter PRECiSE 3 and continued to receive certolizumab pegol 400 mg every 4 weeks for up to 5 years. Patients who relapsed (Crohn's Disease Activity Index [CDAI] score increase ≥70 points or CDAI score ≥350 points) after randomization in PRECiSE 2 were eligible to enter PRECiSE 4 and receive re-induction with certolizumab pegol 400 mg (Weeks 0, 2, 4) followed by maintenance dosing every 4 weeks (i.e., re-induction from PRECiSE 2 into PRECiSE 4 was a single additional dose). In PRECiSE 3 and PRECiSE 4, efficacy was assessed by the Harvey-Bradshaw Index (HBI: remission = HBI score ≤4; response = HBI decrease ≥3).2 Patients lost to follow-up or withdrawn were treated as non-responders. By Week 26 of PRECiSE 2, remission was achieved by 47.9% (103/215) of patients receiving certolizumab pegol (n =215). In an ITT-like analysis of the active arm in which all patients lost to follow up were classified as “failures”, 40.9% (88/215) achieved remission after 12 months of continued treatment in PRECiSE 3. After 18 months, 36.3% (78/215) remained in remission. Among patients that became active and were re-induced with certolizumab pegol in PRECiSE 4, 28.6% (14/49) achieved remission. The remission rate after re-induction was stable (34.7%17/49 6 and 12 months after starting PRECiSE 4). Among patients from the PRECiSE 2 placebo group who were re-induced with certolizumab pegol in PRECiSE 4, 44.0% (33/75) achieved remission. Remission rates were 44.0% (33/75) after 6 months and 36.0% (27/75) after 12 months. No new safety signals were identified following re-exposure of placebo patients from PRECiSE 2 to certolizumab pegol. Certolizumab pegol-induced remission in patients with CD is characterized by a remarkable long-term durability. Re-induction with a single supplemental dose of certolizumab pegol 400 mg after loss of response under certolizumab pegol maintenance was a well-tolerated, successful therapeutic strategy.