Authors' objectives: To assess the effectiveness, safety and cost-effectiveness of antifibrotic therapy for the treatment of patients with idiopathic pulmonary fibrosis (IPF).

Authors' results and conclusions: Effectiveness: Based on the above review, there was sufficient good level of evidences on pirfenidone and nintedanib to be used in the treatment of patients with IPF. Evidence demonstrated that pirfenidone and nintedanib were effective in improving FVC from baseline and slowing rate of FVC decline, compared to placebo in adult patients with IPF. Pirfenidone was effective in lowering risk of decline in percent predicted FVC of ≥10% over one year, compared to placebo in these patients: • In patients with IPF, pirfenidone and nintedanib showed improvement in FVC from baseline, compared to placebo after one year [pirfenidone versus placebo, mean difference (MD) was 0.12 litre (L) (95% credible interval (CrI) 0.03, 0.22 L), and nintedanib versus placebo, MD was 0.11 L (95%CrI 0.00, 0.22 L). • Both pirfenidone and nintedanib significantly slowed the rate of FVC decline compared to placebo (OR 0.62, 95% CrI 0.52, 0.74) and OR 0.4 (95% CrI 0.34, 0.51) respectively. • Patients treated with pirfenidone had lower risk of experiencing a decline in percent predicted FVC of ≥10% over one year (OR=0.58, 95% CrI 0.40, 0.88) whereas there was no significant difference between nintedanib and placebo (OR=0.65, 95% CrI 0.42, 1.02). Pirfenidone demonstrated treatment benefit for mortality outcomes (all-cause and other mortality outcomes; IPF-related mortality, treatment-emergent all-cause mortality, and treatment-emergent IPF-related mortality), progression free survival (reduce risk of disease progression at one year), change from baseline to one year in six-minute walk distance (6MWD) (reducing proportion of patients with a ≥ 50 m decline in 6MWD) and dyspnoea (fewer patients in the pirfenidone group experienced a ≥ 20-point increase in the UCSD SOBQ score or death at one year), compared with placebo. Nintedanib demonstrated benefit in reducing rate of acute exacerbation compared to placebo. Safety: Pirfenidone was approved by the European Medicines Agency for the treatment of mild-to-moderate idiopathic pulmonary fibrosis, approved in several countries (Japan, India, China, and United States). Nintedanib was approved by the United States Food and Drug Administration for use in IPF, and approved in the EU, Canada, Japan, Switzerland, and few other countries. Long term treatment with pirfenidone or nintedanib was reported as safe and generally well tolerated with gastrointestinal and skin related events were commonly reported adverse events following pirfenidone, of which were mostly mild to moderate, while diarrhoea is the most common adverse event reported following nintedanib use. Cost/ cost-effectiveness: In a cost-effectiveness analysis conducted in UK, the ICER ranged from £132,658 to £145,310 per QALY gained for nintedanib and £172,198 to £190,146 per QALY gained for pirfenidone, compared with BSC. In the base case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less cost and more QALY gained. The cost effectiveness acceptability curve showed nintedanib dominates pirfenidone at any threshold level. Adequate informed consent should be obtained prior pirfenidone or nintedanib administration, and sufficient education to patients is required. In Malaysia, a total of 124 patients with IPF were reported since 2017 to September 2020 from three centres (National Respiratory Institute, Hospital Serdang and Hospital Taiping). Out of this, 80 patients were classified as having mild or moderate IPR (64.5%) with the remaining were having severe IPF. The number of mild or moderate IPR cases by year reported from these centres were 18 (2017), 22 (2018), 24 (2019) and 16 (2020), respectively with average of 20 cases reported per year. Estimated annual treatment cost of patients with IPF using pirfenidone is RM50,880, and using nintedanib is RM42,000. Hence, considering this figures, estimated annual treatment cost of using nintedanib or pirfenidone is between RM840,000 to RM1,017,600 for mild or moderate IPF patients in Malaysia. However this estimation is limited by the unavailability of data on number of patients requiring pirfenidone such as those contraindicated to nintedanib.

Authors' recommendations: Based on the above review, nintedanib and pirfenidone may be used in the treatment of patients with mild to moderate IPF. Pirfenidone may be provided as available option for patients such as those contraindicated to nintedanib. The treatment should be initiated and supervised by specialist experienced in diagnosing and treating IPF and adequate informed consent should be obtained prior its administration.

Authors' methods: Studies were identified by searching electronic databases. The following databases were searched through the Ovid interface: MEDLINE(R) In-process and other Non-Indexed Citations and Ovid MEDLINE(R) 1946 to present. EBM Reviews-Cochrane Database of Systematic Reviews (2005 to March 2020), EBM Reviews-Cochrane Central Register of Controlled Trials (March 2020), EBM Reviews – Database of Abstracts of Review of Effects (1st Quarter 2020), EBM Reviews-Health Technology Assessment (1st Quarter 2020), EBM Reviews-NHS Economic Evaluation Database (1st Quarter 2020). The last search was conducted on 31 March 2020. Relevant articles were critically appraised and evidence graded using US / Canadian Preventive Services Task Force.

Project Status: Completed

URL for project: https://www.moh.gov.my/index.php/database_stores/store_view/30?mid=609

Year Published: 2020

URL for published report: https://www.moh.gov.my/index.php/database_stores/store_view_page/30/344

Requestor: Ministry of Health

English language abstract: An English language summary is available

Publication Type: Mini HTA

Country: Malaysia

Organisation Name: Malaysian Health Technology Assessment

Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229

Contact Name: htamalaysia@moh.gov.my

Contact Email: htamalaysia@moh.gov.my

Copyright: Malaysian Health Technology Assessment Section (MaHTAS)