A Model-Based Economic Evaluation of Biologic and Non-Biologic Options for the Treatment of Adults with Moderately-to-Severely Active Ulcerative Colitis after the Failure of Conventional Therapy

Abstract

Background: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. Medical management aims to induce and maintain remission, and to avoid UC complications and the necessity for surgical intervention. Colectomy removes the source of inflammation, but is associated with morbidity and mortality. Newer anti-tumour necrosis factor-(TNF-) therapies may improve medical outcomes albeit at an increased cost.Objective: To assess the incremental cost-effectiveness of infliximab, adalimumab and golimumab versus conventional therapy and surgery from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon.Methods: A Markov model was developed with health states defined according to whether the patient is alive or dead, current treatments received, history of colectomy and level of disease control.Transition probabilities were derived from network meta-analyses (NMAs) of trials of anti-TNFagents in the moderate-to-severe UC population. Health utilities, colectomy rates, surgical complications and resource use estimates were derived from literature. Unit costs were drawn from standard costing sources and literature and were valued at 2013/2014 prices.Results: For patients in whom surgery is an option, colectomy is expected to dominate all medical treatment options. For patients in whom colectomy is not an option, infliximab and golimumab are expected to be ruled out due to dominance, whilst the incremental cost-effectiveness ratio (ICER) for adalimumab versus conventional treatment is expected to be approximately £50,278 per qualityadjusted life year (QALY) gained. Conclusions:Based on the NMAs, the ICERs for anti-TNF-therapy versus conventional treatment or surgery are expected to be at best, in excess of £50,000 per QALY gained. The cost-effectiveness of withdrawing biologic therapy upon remission and re-treating relapse is unknown. KEY POINTS FOR DECISION-MAKERS• Colectomy is expected to be more effective and less expensive than medical treatments for ulcerative colitis.• For patients in whom colectomy is not an acceptable option, the ICERs for anti-TNFtherapy versus conventional treatment are in excess of £50,000 per QALY gained.• Using anti-TNF-therapy to induce remission, withdrawing therapy and re-treating upon relapse, may provide a more economically efficient approach, compared with continuous treatment in those achieving an induction response. The comparative effectiveness and costeffectiveness of this approach is however unclear.3

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan

“…In the study by Wilson et al (2018) for the UK, the time horizon of analysis was lifetime and the QALYs for the biologics ranged between 13.79 and 14.08; in this study by Wilson et al, the health states were not based on response and remission, but on disease severity (moderate-severe, mild, and remission) [18]. The utility value used for patients in remission was 0.87, in line with our analysis and the other studies for the UK, Spain and China [19,46,47]; however, the utility values used by Wilson et al, for the mild and moderate-severe UC health states were 0.80 and 0.68, respectively, which are higher than those for the response-only (0.76) and active UC (0.41 or 0.42) health states used in our analysis and the other studies [19,46,47]. Although Wilson et al used lower utility values compared to our analysis for the surgery, post-surgery remission, and post-surgery complications health states (0.42 vs. 0.66, 0.60 vs. 0.71, and 0.42 vs. 0.66, respectively) [18], the low number of surgeries and complications does not offset the additional QALYs accrued with a higher utility value for the mild and moderate-severe UC health states in the study by Wilson et al versus those used in our analysis for the response-only and active UC health states.…”

“…Only with access to patient-level data is it possible to estimate all the transitions between the maintenance phase health states: remission to remission, remission to responseonly, remission to active UC, response-only to responseonly, response-only to remission, response-only to active UC, active UC to active UC. For example, in the study by Tappenden et al (2016), data relating to response and remission for the comparators included in their analysis were obtained directly from the manufacturer of the biologics, which allowed them to derive all the transition probabilities between the maintenance phase health states for all the comparators [46]. However, most studies will typically have access to the individual patient data from RCTs of one, or at most two, comparators of interest for which all the transition probabilities between the maintenance phase health states can be derived, but meta-analyses and indirect comparisons (e.g., NMA) of relevant RCTs are used to derive the efficacy parameters of the remaining comparators of interest.…”

Replicating Health Economic Models: Firm Foundations or a House of Cards?

“…In order to assess the feasibility of comprehensive model replication, we undertook a small pilot study in which we attempted to fully reproduce five recent economic analyses published in Pharmacoeconomics between August and November 2016 [40][41][42][43][44]. For each study, the feasibility of replicating the analyses was explored through consideration of published information relating to model structure, assumptions and model parameter values (see Table 1) within the full study publication and any supplementary material available online, but excluding information reported in other papers or reports.…”

“…Across the five case studies, our model replication efforts were met with limited success: two models were fully replicated (Versteegh [44] and Tappenden et al [41]), two models were unequivocally not replicable (Oddershede et al [43] and Davies et al [42]), and one model was potentially replicable although the replication process failed in this instance (Elvidge et al [40]). In the two instances whereby the models were reproduced, there were discrepancies between the replicated model results and those reported within the study publications.…”

“…As a consequence of this ambiguity, the replication of the Elvidge et al model was abandoned. With respect to the model by Tappenden et al [41], replication was possible, as the description of the model structure was clear and the list of parameters used in the model was fully reported. However, some reported event probabilities were subject to rounding errors which led to differences between the published results and those generated using the replicated model.…”