Dataset Information

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

ABSTRACT:

Objective

To evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).

Methods

This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ?2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ?8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. Endoscopic evaluations were performed at weeks 0, 10 and 54. The primary outcome was mean change in CDEIS score at week 10; secondary outcome measures included endoscopic response (decrease in CDEIS score >5 points), remission (CDEIS score <6), complete remission (CDEIS score <3) and mucosal healing (no ulcer) at weeks 10 and 54.

Results

In the intention-to-treat population (n=89) the mean±SD CDEIS score was 14.5±5.3 at baseline; the mean decrease in CDEIS score at week 10 was 5.7 (95% CI 4.6 to 6.8, p<0.0001). Rates of endoscopic response, endoscopic remission, complete endoscopic remission and mucosal healing at week 10 were 54%, 37%, 10% and 4%, respectively. At week 54 the corresponding rates were 49%, 27%, 14% and 8%, respectively. The safety profile was consistent with that of previous CZP trials.

Conclusions

Following CZP treatment in patients with active CD, endoscopic lesions were improved as shown by the decrease in mean CDEIS score and by endoscopic response and remission rates. These benefits were achieved as early as week 10 and were generally maintained through week 54.

Clinical trial registration number

NCT00297648.

SUBMITTER: Hebuterne X

PROVIDER: S-EPMC3551215 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

Hébuterne Xavier X Lémann Marc M Bouhnik Yoram Y Dewit Olivier O Dupas Jean-Louis JL Mross Michael M D'Haens Geert G Mitchev Krassimir K Ernault Étienne É Vermeire Séverine S Brixi-Benmansour Hedia H Moreels Tom G TG Mary Jean-Yves JY Marteau Philippe P Colombel Jean-Frédéric JF

Gut 20120423 2

<h4>Objective</h4>To evaluate the efficacy of certolizumab pegol (CZP) in improving endoscopic lesions in patients with active ileocolonic Crohn's disease (CD).<h4>Methods</h4>This phase IIIB multicentre open-label clinical trial enrolled 89 adult patients with active endoscopic disease (ulceration in ≥2 intestinal segments with a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥8 points). Patients received subcutaneous CZP 400 mg at weeks 0, 2 and 4 and every 4 weeks up to week 52. E ...[more]

PMID: 22525883

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Project description:BACKGROUND:Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-?) inhibitor which regulates impaired immune response. OBJECTIVES:The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. SEARCH METHODS:We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. SELECTION CRITERIA:We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. DATA COLLECTION AND ANALYSIS:We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ?150), clinical response at week 8 (CDAI reduction ? 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). MAIN RESULTS:Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. AUTHORS' CONCLUSIONS:Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

Project description:IntroductionCertolizumab pegol (CZP), an Fc-free, PEGylated anti-tumour necrosis factor biologic, dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks, resulted in improvements in Japanese patients with moderate to severe plaque psoriasis (PSO); no new safety signals were identified. We present 52-week efficacy and safety results.MethodsPatients ≥ 20 years with PSO ≥ 6 months [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area ≥ 10%, Physician's Global Assessment (PGA) ≥ 3] were randomised 1:2:2 to placebo Q2W, CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks. Week 16 PASI 50 responders continued through week 52; CZP 200 mg Q2W-randomised patients were re-randomised 1:1 to CZP 200 mg Q2W or CZP 400 mg Q4W; patients initially randomised to other treatment groups continued in the same group. Outcomes included PASI 75/90/100, PGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Itch Numeric Rating Scale (INRS) 0, modified Nail Psoriasis Severity Index (mNAPSI), durability of response for week 16 PASI 75/90 responders, and safety.ResultsOf 26/53/48 patients randomised to placebo, CZP 400 mg Q2W and CZP 200 mg Q2W, 2/47/39 completed week 52, respectively. PASI 75/90 responses were generally maintained from weeks 16 to 52 for all CZP doses. Most week 16 PASI 75/90 achievers maintained their response through week 52. PASI 75/90/100 responses at week 52 in the CZP 400 mg Q2W and CZP 200 mg Q2W groups were 83.0/81.1/41.5% and 72.9/60.4/18.8%, respectively; DLQI/INRS remission rates were 64.2/50.9% in CZP 400 mg Q2W and 58.3/27.1% in CZP 200 mg Q2W-treated patients. Reductions in mNAPSI observed for CZP-treated groups were maintained through week 52. No new safety signals were identified.ConclusionCZP treatment resulted in improvements in signs and symptoms of PSO, which were maintained through week 52. The 400 mg Q2W dose could provide additional clinical benefit.Trial registrationNCT03051217.

Project description:IntroductionWe present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217).MethodsPatients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician's Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used.ResultsOf the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0-23.7 kg/m2)/intermediate (> 23.7-27.4 kg/m2)/high (> 27.4-47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0-18.0)/intermediate (> 18.0-27.0)/high (> 27.0-67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1.ConclusionClinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups.Trial registrationClinicalTrials.gov identifier, NCT03051217.

Project description:IntroductionCertolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications.MethodsWe report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician's Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0-16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1.ResultsA total of 127 patients were randomized to CZP 400 mg Q2W (N = 53), CZP 200 mg Q2W (N = 48), placebo (N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p < 0.0001 for both CZP doses versus placebo). Significant improvements in DLQI and INRS were reported at week 16 by patients receiving both CZP doses compared with placebo (p < 0.0001). Incidence of treatment-emergent adverse events within the CZP 400 mg Q2W, CZP 200 mg Q2W, and placebo groups were 326.1, 404.9, and 682.4 per 100 patient-years. No new safety signals were identified compared to previously reported data.ConclusionCZP dosed at 400 mg or 200 mg Q2W was associated with improved PSO signs and symptoms.Trial registrationClinicalTrials.gov identifier, NCT03051217.

Dataset Information

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

Objective

Methods

Results

Conclusions

Clinical trial registration number

Publications

Endoscopic improvement of mucosal lesions in patients with moderate to severe ileocolonic Crohn's disease following treatment with certolizumab pegol.

Similar Datasets

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