The effectiveness and cost-effectiveness of treatments for idiopathic pulmonary fibrosis: systematic review, network meta-analysis and health economic evaluation

Abstract

BackgroundIdiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease with considerable impact on patients and carers as the disease progresses. Currently few treatments are available. We aimed to evaluate the clinical and cost-effectiveness of available treatments for IPF.MethodsSystematic reviews of clinical effectiveness, quality of life and cost effectiveness were undertaken. Eleven bibliographic databases were searched from inception to July 2013 and studies were assessed for eligibility against a set of pre-defined criteria. Two reviewers screened references, extracted data from included studies and appraised their quality. An advisory group was consulted about the choice of interventions. A narrative review was undertaken and where feasible fixed effect and random effects meta-analysis were undertaken including a network meta-analysis (NMA).A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Following best practice recommendations, the model perspective was of the national health service and personal social services, a discount rate of 3.5% for costs and health benefits was applied and outcomes were expressed as cost per quality adjusted life-year gained. Parameter values were obtained from the NMA and systematic reviews. Sensitivity analyses were undertaken.ResultsFourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine [NAC] (alone or in combination), four pirfenidone, one nintedanib, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good. Evidence suggests that some effective treatments are available. In NMA only nintedanib and pirfenidone show statistically significant improvements. The model results show increased survival for five pharmacological treatments (NAC triple therapy, inhaled NAC, nintedanib, pirfenidone, and sildenafil) compared with best supportive care, at increased cost. Only inhaled NAC was cost-effective at current willingness to pay thresholds but it may not be clinically effective.ConclusionsFew interventions have any statistically significant effect and the cost-effectiveness of treatments is uncertain. A lack of studies on palliative care approaches was identified and there is a need for further research into pulmonary rehabilitation and thalidomide in particular. A well conducted RCT on inhaled NAC therapy should also be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/2050-6511-15-63) contains supplementary material, which is available to authorized users.

Current best practice in rehabilitation in interstitial lung disease

“…An important area for future research is the effect of PR on healthcare costs. Although the clinical effectiveness of PR in ILD is increasingly understood, clarification of cost effectiveness of PR would provide impetus for commissioners and policy makers to ensure this intervention is widely available [Loveman et al 2014]. The NICE clinical guideline of IPF has begun this process by modelling the cost effectiveness of PR, suggesting that it could be cost effective to deliver this intervention every 6-12 months, which could make it possible for PR to be a standard treatment in IPF [NICE, 2013].…”

Therapy for idiopathic pulmonary fibrosis: lessons from pooled data analyses

“…Tolerance data were also evaluated in the meta-analysis of IPF and hypersensitivity pneumonitis patients by JIANG et al [17], demonstrating increased risks of mild gastrointestinal, dermatological and neurological complaints. A subsequent network meta-analysis, looking at the effectiveness of various treatments for IPF, including pirfenidone and nintedanib, showed that only these two therapies were of significant benefit [18]. The limitations of this form of analysis were the indirect comparison of treatments not formally assessed in head-to-head trials and the combination of different end-points to gauge efficacy.…”

Targeted Therapy for Idiopathic Pulmonary Fibrosis: Where To Now?

“…Third, among the other unknowns are the utility of either drug in patients with advanced IPF and/or advanced age with varied comorbidities. Fourth, there are concerns that the drugs may not be cost-effective, at least in the prevalent health-care delivery systems in some countries [37]. Lastly, these drugs will alter the design of future studies of newer drugs with the requirement for a new standard-of-care (control) arm in randomized clinical trials.…”