Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis

Abstract

Background Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion. Research question The data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015–2016. Study design and methods Patients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. Results During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3–2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0–1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6–0.9). Interpretation This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.

Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: a retrospective cohort study

“…In SA2 the treatment discontinuation was rather high, with 50.7% of pirfenidone-treated and 44.0% of nintedanib-treated patients. Similar high discontinuation rates were also reported in other claims data based studies [ 12 , 13 , 34 ]. One possible explanation for the difference in the discontinuation rates between the drugs in our study is that nintedanib was approved during the study period.…”

“…The population included was comparable to ours in terms of space of time, data source (insurance data base), and age of patients. However, a recently published study with data from the French National Health System reported a greater risk of all-cause mortality in nintedanib-treated patients [ 13 ]. The study covered a similar time horizon, sample size, population’s age, and sex distribution as our study.…”

“…Corral et al also described a lower respiratory-related hospitalization risk for pirfenidone-treated patients with a reported HR of 0.71 (95% CI: 0.57; 0.90). Similarly, Belhassen et al also reported a greater risk of respiratory-related hospitalizations for nintedanib-treated patient with an HR of 1.3 (95% CI: 1.0; 1.7) [ 13 ]. The different results for respiratory-related hospitalizations compared to our study might be explained by different definitions of the outcome, as different conditions were considered to be respiratory-related in each study.…”

“…Although the study included a large sample, it had a short observation period and did not compare mortality differences between the drugs. A recently published study with data from the French National Health System [ 13 ] also reported an association between pirfenidone treatment and lower respiratory-related hospitalizations. However, all-cause hospitalizations were not investigated.…”

“…So far, however, there is no guideline recommendation which drug should be preferred over the other [ 10 ], as no randomized controlled trials (RCT) comparing the two drugs have been conducted. Comparative observational studies, especially in real world settings are also rare and show inconclusive results on survival differences between the drugs [ 11 – 13 ]. A claims data-based study among Medicare enrollees suggested that pirfenidone treatment is associated with fewer all-cause and fewer respiratory-related hospitalizations and thus lower inpatient costs compared to nintedanib treatment [ 15 ].…”