Dataset Information

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

ABSTRACT:

Background

There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial.

Methods

A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective. Using short-term trial data, a Markov model (MM) was then developed and evaluated over further 18 years. Both DT and MM were combined to investigate cost-effectiveness of infliximab versus ciclosporin for ASUC patients over 20-year time horizon, with a rigorous multiple deterministic and probabilistic sensitivity analyses to address uncertainty in results.

Results

The decision tree mirrored trial-based results. Beyond 2-year trial follow-up, Markov model predicted a decrease in colectomy rate, but it remained slightly higher for ciclosporin. NHS costs and quality adjusted life years (QALYs) over base-case 20 year time horizon were £26,793 and 9.816 for ciclosporin and £34,185 and 9.106 for infliximab, suggesting ciclosporin dominates infliximab. Ciclosporin had 95% probability of being cost-effective at a willingness-to-pay (WTP) threshold value up to £20,000.

Conclusion

Using data from a pragmatic RCT, the cost-effectiveness models produced incremental net health benefit in favour of ciclosporin relative to infliximab. Results from long-term modelling indicated that ciclosporin remains dominant compared with infliximab for the treatment of NHS ASUC patients, however, these need to be interpreted cautiously.

Trial registration

CONSTRUCT Trial registration number ISRCTN22663589; EudraCT number: 2008- 001968-36 (Date 27/08/2008).

SUBMITTER: Alam MF

PROVIDER: S-EPMC9993375 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

Alam Mohammed Fasihul MF Longo Mirella M Cohen David D Groves Sam S Alrubaiy Laith L Hutchings Hayley A HA Watkins Alan A Sebastain Shaji S Williams John G JG

BMC health services research 20230308 1

<h4>Background</h4>There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial.<h4>Methods</h4>A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUC ...[more]

PMID: 36890533

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Project description:BackgroundInfliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness.MethodsIn this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589.FindingsBetween June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group vs 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group vs 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group vs 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab vs ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients vs 25 in 17 patients); or deaths (three in the infliximab group vs none in the ciclosporin group).InterpretationThere was no significant difference between ciclosporin and infliximab in clinical effectiveness.FundingNIHR Health Technology Assessment programme.

Project description:IntroductionMany patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC.Methods and analysisBetween May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants' scores, analysed by Cox regression. Secondary outcome measures include: the CCQ-an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures-EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants' views on therapies for acute severe UC and healthcare professionals' views on the two drugs and their administration.Ethics and disseminationThe Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals.Trial registration number isrctn22663589; EudraCT number: 2008-001968-36.

Project description:Background: In steroid-refractory acute severe ulcerative colitis (ASUC), cyclosporine (CYS) or infliximab (IFX) may be considered as a second-line alternative to avoid colectomy. There are short-term data reported, but until now, there is no meta-analysis regarding long-term outcomes of CYS and IFX in patients with ASUC. Aim: To compare long-term efficacy and safety of CYS and IFX in a meta-analysis. Methods: Three electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials) were searched for studies which compared CYS vs. IFX in adults with ASUC. Long-term colectomy-free rate from 1 to 10 years during CYS or IFX therapy was collected, last updated up to 22nd May 2019. Primary outcome was long-term colectomy-free rate, secondary outcomes were adverse events (AE), serious adverse events (SAE), and mortality. Long-term colectomy-free survival and safety measures were pooled with the random-effect model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Data from 1,607 patients in 15 trials were extracted. In the first 3 years, pooled OR for colectomy-free survival was higher with IFX than with CYS (OR = 1.59, 95% CI: 1.11-2.29, p = 0.012; OR = 1.57, 95% CI: 1.14-2.18, p = 0.006; and OR = 1.75, 95% CI: 1.08-2.84, p = 0.024; at 1, 2, and 3 years, respectively). However, the significant difference remained undetected from the fourth year of follow-up and in subgroup of RCTs (OR = 1.35, 95% CI: 0.90-2.01, p = 0.143; OR = 1.41, 95% CI: 0.94-2.12, p = 0.096; and OR = 1.34, 95% CI: 0.89-2.00, p = 0.157; at 1, 2, and 3 years, respectively). No significant difference was detected regarding adverse events, serious adverse events and mortality between the groups. The neutral associations proved to be underpowered with trial sequential analysis. Conclusion: However observational studies show IFX as a better choice, according to the RCTs, choosing either CYS or IFX as rescue therapy for ASUC, the long-term outcomes are not different, although further large RCTs are warranted.

Project description:Objective: To evaluate the cost effectiveness of vedolizumab vs. infliximab in the treatment of anti-tumor necrosis factor-alpha (TNF-α)-naïve patients with moderate-to-severe active ulcerative colitis (UC) in China. Methods: The costs and effectiveness of vedolizumab and infliximab in the treatment of anti-TNF-α naïve patients with moderate-to-severe active UC were compared using a hybrid decision tree model and a Markov model. From the perspective of the Chinese healthcare system, this study simulated the lifetime health benefits [quality-adjusted life-years (QALYs)] and costs (USD) for patients with UC from the induction phase to the maintenance phase, with an annual discount rate of 5%. The clinical efficacy and transition probability data were based on a previously published network meta-analysis. The health utility, surgical risk, biologic drug discontinuation rate, and mortality were derived from previous literature and the Chinese statistical yearbook. The cost data were based on China's drug purchase and biding platform and the results of a survey sent to clinicians in 18 tertiary hospitals. One-way and probabilistic sensitivity analyses (PSAs) were performed to validate the robustness of the models' assumptions and specific parameter estimates. Results: The results of the base-case analyses showed that compared with infliximab, vedolizumab led to a gain of 0.25 QALYs (9.56 vs. 9.31 QALYs) and was less expensive by $7,349 ($180,138 vs. 187,487), indicating that the use of vedolizumab was a dominant strategy. The results of one-way sensitivity analyses suggested that the annual discount rate and health-state costs had the greatest impact, but the results were otherwise consistent with those of the base-case analyses. The PSAs suggested that vedolizumab had a 98.6% probability of being effective at a threshold of 3 times the gross domestic product (GDP) per capita in China in 2020. Conclusion: Compared with infliximab, vedolizumab appears to be a more cost-effective option in the treatment of anti-TNF-α naïve adult patients with moderate-to-severe, active UC in China.

Dataset Information

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

Background

Methods

Results

Conclusion

Trial registration

Publications

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

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