Discussion
’, ASUC, UC, IBD, ’ drug
EVENTS, DISEASE, REMISSION, INFLAMMATORY BOWEL DISEASE
We developed and used decision analytical models to investigate long-term cost-effectiveness of infliximab versus ciclosporin in the management of steroid-resistant ASUC patients. The study used data from the RCT to extrapolate colectomy beyond the trial follow up and to estimate its health effect (QALYs) and resource use implications over 20 years time horizon. Results from both decision tree and Markov models suggest that ciclosporin is more effective in terms of QALY gain and less costly than infliximab. Although the difference in QALYs between two groups was not statistically significant in within-trial analyses, infliximab appeared to be significantly more costly in terms of the NHS healthcare costs [An evidence review committee of NICE expressed concerns over the uncertainty in clinical effectiveness of the treatments, e.g. colectomy rates, due to very small number of RCTs, which themselves were small, and to criticism of the use of evidence from mixed treatment comparisons [The short-term decision tree model with 2-year time horizon has produced similar cost-effectiveness results to those from a 24-month ‘within-trial’ analysis, reflecting an internal validity of the model and its results [The model predicted the risk of colectomy among UC patients beyond 2-year follow up period, hence, its long-term implications on both QALYs and costs. Given a very few patients had colectomy after 24 months, we based our time-to-colectomy survival analysis using 24 months follow-up data so that a better prediction in the right-hand tail of survival curves would be achieved. However, this remained as one of the study limitations. An RCT with relatively a higher sample size could potentially reduce this limitation. Another limitation of the study is—not considering a societal cost perspective, resulting in a potentially conservative approach. Indirect costs such as absence from work due to the disease were not considered in the study, which fall outside the healthcare sectors. However, indirect costs may exceed direct costs since IBD is generally diagnosed in early adulthood or middle-age with relatively more productivity among this population [Arguably hospitals’ drug acquisition costs for infliximab might be significantly lower than the BNF listed price. This is due to fact that a drug company may negotiate a price below its cost in order to get more future business from hospitals in the region, nevertheless, the negotiated price would not represent its value. The principle in economic evaluation is to put a money value on a healthcare resource not to measure the cash paid for it. However, the study provides the potential changes in infliximab biosimilars’ price and its impact on cost-effectiveness results through robust sensitivity analyses, which favours ciclosporin as a cost-effective treatment option.Beyond 2-year follow-up, ciclosporin remained more effective and less costly than infliximab over 18-year time horizon, irrespective of varied risk of colectomy between groups in the model. Although the model projected slightly higher colectomy rates for ciclosporin patients, in line with higher within-trial colectomies for this group, the estimated ‘overall’ higher cost for infliximab group is due to its associated higher average cost of ‘remission from medicine’ health state that is propagated through the Markov model. Another likely explanation of higher average costs associated with infliximab group is that treatment with ciclosporin tended to be stopped by 12 weeks, whereas those on infliximab tended to continue treatment for longer. This was at the discretion of the attending physician and reflected the pragmatic nature of the trial [In our cost-effectiveness model, mortality from different health states is considered from a published study which showed small but higher mortality for ‘no colectomy’ than ‘emergency colectomy’ UC patients [By combining the decision tree with the long-term Markov model, base-case cost-effectiveness results suggested that ciclosporin dominates infliximab. The base-case cost effectiveness results were remained robust to changes in different factors, which can be seen from deterministic one-way sensitivity analyses. Overall, this confirms that ciclosporin appears to be more cost-effective treatment for ASUC patients in the UK, however, the difference in costs between two treatment options is apparent globally [The study is based on utility values from 3-year follow up data collected in the CONSTRUCT trial, which showed an utility decrement among colectomy patients in the short term. Given higher colectomies in ciclosporin patients, this in fact disfavours ciclosporin, compared to infliximab, in terms of utility gain. However, in the long term surgery did not result in decrement in quality of life for UC patients [Our results differ from those found in a model-based study by Punekar and Hawkins [Standard parametric models are generally fitted to time-to-event data from trials for future projection of health events such as colectomy. However, there are inherent and unavoidable limitations in estimating parametric functions as not enough data available from short follow-ups to compare long-term outcomes from the model [It is evident from observational studies that the cumulative rate of colectomies increases over time with both infliximab and ciclosporin [In a recent guideline, commissioned by the British Society of Gastroenterology (BSG), for the management of inflammatory bowel disease (IBD) in adults, the committee members recommended that ASUC patients not responding to corticosteroid should be treated with intravenous infliximab or ciclosporin who have not failed a previous thiopurine therapy [Infliximab is more expensive, but has been widely used due to its simpler administration. Because of the availability of new anti-TNF biosimilars in the market, the cost of infliximab has been falling [