Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study

Abstract

Real-world studies include a broader patient population for a longer duration than randomised controlled trials (RCTs) and can provide relevant insights for clinical practice.PASSPORT was a multicentre, prospective, post-authorisation study of patients who were newly prescribed pirfenidone and followed for 2 years after initiating treatment. Physicians collected data on adverse drug reactions (ADRs), serious ADRs (SADRs) and ADRs of special interest (ADRSI) at baseline and then every 3 months. Post hoc stepwise logistic regression models were used to identify baseline characteristics associated with discontinuing treatment due to an ADR.Patients (n=1009, 99.7% with idiopathic pulmonary fibrosis) had a median pirfenidone exposure of 442.0 days. Overall, 741 (73.4%) patients experienced ADRs, most commonly nausea (20.6%) and fatigue (18.5%). ADRs led to treatment discontinuation in 290 (28.7%) patients after a median of 99.5 days. Overall, 55 (5.5%) patients experienced SADRs, with a fatal outcome in six patients. ADRSI were reported in 693 patients, most commonly gastrointestinal symptoms (38.3%) and photosensitivity reactions/skin rashes (29.0%). Older age and female sex were associated with early treatment discontinuation due to an ADR.Findings were consistent with the known safety profile of pirfenidone, based on RCT data and other post-marketing experience, with no new safety signals observed.

Patient journey and treatment patterns in adults with IPF based on health care data in Sweden from 2001 to 2015

“…Adverse events (AEs) following treatment initiation can be another reason for the low treatment adherence. AEs are the primary drivers of treatment discontinuation in pirfenidone-treated patients [41], majority of which occur during the first 6 months of treatment [42]. In this study too, a large proportion of discontinuation occurred within the first 6 months of treatment initiation (Fig.…”

Guidelines of the Polish Respiratory Society for Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis

“…This posed several important questions to pulmonologists, for instance, which of the agents should be used first and when switching from one agent to the other should be considered. Long-term open-label studies, pooled analyses of earlier randomised clinical studies and real-world data confirmed the beneficial safety and tolerability profiles of both pirfenidone [237,238,271,272] and nintedanib [242,267]. However, in a certain percentage of patients -in spite of dose adjustments, interruptions or symptomatic management -the treatment is discontinued because of persistent adverse effects.…”

“…If necessary, it is possible to reduce the pirfenidone dose or transiently interrupt the treatment, with no negative effects on its efficacy [237]. PASSPORT, a study designed to assess long-term safety of pirfenidone, failed to reveal any new adverse effects of the drug in addition to those already observed in randomised trials [238]. Contraindications include individuals diagnosed with hypersensitivity to the active substance or to any of the excipients; patients with a history of angioedema following pirfenidone administration; cases where simultaneous use of fluvoxamine is necessary; serious hepatic dysfunction or end-stage liver disease; and serious renal dysfunction with endogenous creatinine clearance < 30 mL/min or requiring dialysis therapy.…”

Efficacy, safety, and tolerability of combined pirfenidone and N-acetylcysteine therapy: A systematic review and meta-analysis

“…Gastrointestinal (diarrhoea, anorexia, etc.) and skin side effects (photosensitivity and skin rash) are the most common adverse effects experienced by IPF patients receiving PFD treatment [27,28] . Compared to the findings from the PANORAMA trial, our meta-analysis showed a similar rate of side effects except for skin side effects (lower rate).…”