Switching antifibrotics in patients with idiopathic pulmonary fibrosis: a multi-center retrospective cohort study

Abstract

Background Currently, there are two antifibrotics used to treat idiopathic pulmonary fibrosis (IPF): pirfenidone and nintedanib. Antifibrotics slow disease progression by reducing the annual decline of forced vital capacity (FVC), which possibly improves outcomes in IPF patients. During treatment, patients occasionally switch antifibrotic treatments. However, prognostic implication of changing antifibrotics has not yet been evaluated. Methods This multi-center retrospective cohort study examined 262 consecutive IPF patients who received antifibrotic therapy. Antifibrotic agents were switched in 37 patients (14.1%). The prognoses were compared between the patient cohort that switched antifibrotics (Switch-IPF) and those without (Non-Switch-IPF) using propensity-score matched analyses. Results The median period between the initiation of antifibrotic therapy and the drug switch was 25.8 (12.7–35.3) months. The most common reasons for the switch were disease progression (n = 17) followed by gastrointestinal disorders (n = 12). Of the 37 patients that switched antifibrotics, only eight patients disrupted switched antifibrotics by their adverse reactions. The overall prognosis of the Switch-IPF cohort was significantly better than the Non-Switch-IPF cohort (median periods: 67.2 vs. 27.1 months, p < 0.0001). In propensity-score matched analyses that were adjusted to age, sex, FVC (%), history of acute exacerbation, and usage of long-term oxygen therapy, the Switch-IPF cohort had significantly longer survival times than the Non-Switch-IPF group (median 67.2 vs. 41.3 months, p = 0.0219). The second-line antifibrotic therapy showed similar survival probabilities than those in first-line antifibrotic therapy in multistate model analyses. Conclusion Switching antifibrotics is feasible and may improve prognosis in patients with IPF. A further prospective study will be required to confirm clinical implication of switching the antifibrotics.

Pharmakotherapie der idiopathischen Lungenfibrose (ein Update) und anderer progredienter pulmonaler Fibrosen

“…In mehreren retrospektiven Studien wurden IPF-Patientenkollektive untersucht, bei denen eine Umstellung der antifibrotischen Therapie erfolgt ist 38 40 174 175 176 .…”

“…Als Progression wurde in dieser Analyse ein Abfall von FVC (%pred) > 5 % in 6 Monaten gewertet oder ein Abfall FVC (%pred) < 5 % bei gleichzeitiger Verschlechterung der Symptome oder des radiologischen Befundes 38 . Suzuki et al analysierten ein Kollektiv von 262 antifibrotisch behandelten IPF-Patienten 174 . Bei 37 Patienten (14 %) wurde ein Therapiewechsel (Pirfenidon zu Nintedanib n = 29; Nintedanib zu Pirfenidon n = 8) vollzogen (46 % bei Progress, 46 % bei Antifibrotika-Nebenwirkungen, 8 % bei Erstdiagnose Lungenkarzinom, vasospastischer Angina oder explizitem Patientenwunsch).…”

“….1 Bei IPF In mehreren retrospektiven Studien wurden IPF-Patientenkollektive untersucht, bei denen eine Umstellung der antifibrotischen Therapie erfolgt ist[38,40,[174][175][176].In einer retrospektiven Multizenter-Analyse wurden 62 IPF-Patienten analysiert, die mit Nintedanib behandelt wurden. 48 Patienten aus diesem Kollektiv waren mit Pirfenidon vorbehandelt worden.…”

Geriatric Nutritional Risk Index is a predictor of tolerability of antifibrotic therapy and mortality risk in patients with idiopathic pulmonary fibrosis

“…Further, nintedanib was found to have similar efficacy in patients with progressive fibrotic ILD other than IPF 7 . Adverse drug reactions (ADRs) are frequently experienced by patients who are prescribed antifibrotic drugs, sometimes resulting in the discontinuation of these drugs 8–10 . Among ADRs, gastrointestinal disorders including appetite loss, diarrhoea, and weight loss are frequently seen during antifibrotic therapy.…”

Radiological and Physiological Predictors of IPF Mortality

“…Several physiological [ 9 , 10 ] and radiological measures, such as forced vital capacity (FVC) diffusion capacity of the lung for carbon monoxide (DLco), traction bronchiectasis, and honeycombing have been reported as useful predictors of IPF mortality [ 11 , 12 ]. IPF has a variable clinical course, which ranges from asymptomatic to severe irreversible respiratory failure along with acute exacerbation [ 13 ].…”