Cem Kayhan

Long‐term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7‐year results from the PRECiSE 3 study

The efficacy and safety of certolizumab pegol (CZP) in moderate‐to‐severe Crohns disease were demonstrated in two 26‐week double‐blind studies (PRECiSE 1 & 2).

Reinduction with Certolizumab Pegol in Patients with Crohn's Disease Experiencing Disease Exacerbation: 7-year Data from the Precise 4 Study

Background:Patients with Crohns disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2. Methods:Patients eligible for PRECiSE 4 had Crohns disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy. Results:Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohns disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient-years was 6.11 for serious infections and 1.29 for malignancies. Conclusions:Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings.

Efficacy of Certolizumab Pegol in Crohn's Disease: Response to Ford et al.

To the Editor: In a recent meta-analysis, Ford et al. ( 1 ) reported results of an analysis of pooled data from randomized, controlled trials of anti-tumor necrosis factor (TNF) biological therapies in infl ammatory bowel disease (IBD), to determine relative risk (RR) of failure to achieve remission in active disease and RR of relapse of acti vity in quiescent disease once remission had occurred with these agents. Th e authors indicated they used very conservative methodology in order to minimize over estimation of effi cacy of biological therapies. Th is approach concluded that, overall, anti-TNF agents are eff ective in inducing remission in moderate to severely active Crohn ’ s disease (CD), but that the most evidence of benefi t was obtained with infl iximab (IFX), adalimumab (ADA), and natalizumab compared with certolizumab pegol (CZP). Statistical analyses adjusted for the dosing schedule of the anti-TNF agents used indicated that in the case of CZP 400 mg, this agent was of borderline signifi cance vs. placebo (RR = 0.94; confi dence interval 0.89 – 1.00, P = 0.05). Th e authors of this letter would like to make two points in response to the fi ndings reported by Ford et al. First, the design and purpose of the CZP trials from which data were combined for these analyses were quite diff erent, raising a concern regarding the validity of combining disparate data. Specifi cally, the earlier phase 2 trials were single-dose ( 2 ) or multiple-dose ( 3 ) studies, and were neither CONFLICT OF INTEREST Th e authors are employees of UCB.