Effect of pirfenidone in patients with more advanced idiopathic pulmonary fibrosis.

Data from controlled clinical studies in patients with more advanced idiopathic pulmonary fibrosis (IPF) could inform clinical practice, but they are limited, since this sub-population is usually excluded from clinical trials. These exploratory post-hoc analyses of the open-label, long-term extension study RECAP (NCT00662038) aimed to assess the efficacy and safety of pirfenidone in patients with more advanced IPF. Patients were categorised according to the extent of lung function impairment at baseline: more advanced (percent predicted FVC <50% and/or DLco <35%) and less advanced (percent predicted FVC ≥50% and DLco ≥35%).Overall, 596 patients with baseline FVC and/or DLco values available were included in the analyses; 187 patients had more advanced disease, and 409 patients had less advanced disease. Mean percent predicted FVC declined throughout 180 weeks of treatment in both more and less advanced disease subgroups. Both subgroups exhibited a similar pattern of adverse events; however, adverse events related to IPF progression were experienced by a higher proportion of patients with more advanced versus less advanced disease. Discontinuation rates due to any reason, adverse events related to IPF progression, or deaths were each higher in the more advanced versus the less advanced disease subgroup.These analyses found that longer-term pirfenidone treatment resulted in a similar rate of lung function decline and safety profile in patients with more advanced versus less advanced IPF, and the data suggest that pirfenidone is efficacious, well tolerated, and a feasible treatment option in patients with more advanced IPF.

Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis.

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1) in patients with idiopathic pulmonary fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day-1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs.Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.

Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials.

INTRODUCTION: Temporary dose modifications, such as reductions or interruptions, may allow patients to better manage adverse events (AEs) associated with pirfenidone use and continue treatment for idiopathic pulmonary fibrosis (IPF). However, the impact of such dosing adjustments on efficacy and safety is uncertain. METHODS: Patients randomised to receive treatment with pirfenidone 2403 mg/day or placebo in the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY (Study 004 (NCT00287716)) and Study 006 (NCT00287729))) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND (Study 016 (NCT01366209)) trials were included in the analysis (n=1247). Descriptive statistics and a linear mixed-effects model (slope analysis) for annual rate of decline in forced vital capacity (FVC) by dose intensity were performed. Treatment-emergent AEs (TEAEs) were summarised and grouped by dose intensity or body size. RESULTS: Dose reductions and interruptions occurred in 76.9% (95% CI 73.4% to 80.1%) and 46.5% (95% CI 42.6% to 50.6%) of patients receiving pirfenidone vs 72.0% (95% CI 68.3% to 75.4%) and 31.1% (95% CI 27.5% to 34.9%) of patients receiving placebo, respectively. Dose interruptions tended to occur during the first 6 months of treatment, whereas dose reductions exhibited more variability. Less FVC decline from baseline was observed in patients receiving pirfenidone versus placebo at >90% dose intensity (p<0.001) or ≤90% dose intensity (p=0.0191), showing treatment benefit in both subgroups of dose intensity. No meaningful relationship between weight and TEAEs was observed. CONCLUSION: Dose interruptions, which may be required to manage TEAEs, mostly occurred during the first 6 months of treatment. Despite dose reductions and interruptions, most patients with IPF maintained relatively high dose intensity on pirfenidone, without compromising its treatment effect compared with placebo. TRIAL REGISTRATION NUMBERS: NCT00287729, NCT00287716, NCT01366209.

Resource utilisation and clinical data before and after switching between short-acting human insulin and rapid-acting insulin analogues in patients with type 2 diabetes: the SWING study.

AIM: SWING was a prospective, observational study conducted in nine European countries primarily to assess direct treatment costs when switching from short-acting human insulins to rapid-acting insulin analogues (H-A) or vice versa (A-H) in patients with type 2 diabetes. METHODS: Data were collected at a baseline visit (time of switch) and at approximately 3, 6 and 12 months post-switch. RESULTS: In total, 2389 patients switched from H-A (n=2203) or A-H (n=186); another 603 were enrolled but ineligible. Mean (SD) direct diabetes-related costs (pro-rated to account for variable visit schedules) were €548.7 (865.8) 6 months prior to switch, €625.6 (1474.9) at 0-6 months and €568.6 (590.7) 6-12 months following switch for H-A, and €544.5 (421.0), €481.0 (301.5) and €461.6 (335.0) for A-H, respectively. Mean (SD) HbA(1c) decreased over 12 months by 1.08 (1.53)% units H-A and 1.17 (1.45)% units A-H. A small decline in hypoglycaemia occurred over time, but there were no clinically meaningful changes in mean PROs. CONCLUSIONS: There were small changes in mean direct diabetes-related costs (following adjustment for time interval) in patients switching in either direction. Improvements in mean HbA(1c) and incidence of hypoglycaemia cannot necessarily be attributed to therapeutic switch.