John Stauffer

FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis.

FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis. This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks. FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function. Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway. FG-3019 demonstrated good outcomes in changes in pulmonary function and extent of pulmonary fibrosis in IPF http://ow.ly/Xn7B4

FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in IPF

FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis. This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks. FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function. Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway. FG-3019 demonstrated good outcomes in changes in pulmonary function and extent of pulmonary fibrosis in IPF http://ow.ly/Xn7B4

Pirfenidone Reduces Respiratory-related Hospitalizations in Idiopathic Pulmonary Fibrosis

Rationale: Respiratory‐related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes. Objectives: To compare the risk of nonelective hospitalization by type (all‐cause, respiratory related, and non‐respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials. Methods: Individual patient data was pooled from three phase III randomized, placebo‐controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time‐to‐event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity. Measurements and Main Results: A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory‐related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36‐0.77; P = 0.001), but all‐cause (HR, 0.91; 95% CI, 0.70‐1.19; P = 0.528) or non‐respiratory‐related hospitalization (HR, 1.32; 95% CI, 0.92‐1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow‐up. Conclusions: In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory‐related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Using key strategies to prevent and manage pirfenidone-related AEs can help maximise adherence to pirfenidone http://ow.ly/Veyk30gsFTs

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. Combined pirfenidone and nintedanib was tolerated by the majority of patients with IPF, encouraging further study http://ow.ly/1Iq030kaZuD

P173 Reduction in non-elective respiratory-related hospitalizations in patients treated with pirfenidone: pooled analyses from three phase 3 trials of pirfenidone in idiopathic pulmonary fibrosis

Rationale Patients with idiopathic pulmonary fibrosis (IPF) are frequently hospitalised for a variety of reasons. Respiratory-related hospitalizations may occur because of acute exacerbations of IPF, respiratory tract infections, respiratory failure and other causes. Regardless of cause, respiratory-related hospitalizations have been linked to poor outcomes in patients with IPF. We describe the proportion of patients from the three Phase 3 pirfenidone IPF trials with at least one non-elective hospitalisation (all-cause, respiratory-related and non-respiratory-related) over 12 months. Methods In three Phase 3 randomised, placebo-controlled studies of pirfenidone for IPF (CAPACITY I/II and ASCEND), patients were randomised to pirfenidone (2403 mg/day) or placebo. In the two CAPACITY studies, respiratory-related hospitalizations were a pre-specified endpoint. In ASCEND, hospitalizations were reported as adverse events (AEs), and retrospectively categorised as respiratory-related or non-respiratory by case review. The pooled rates of patients experiencing ≥1 non-elective hospitalizations (all-cause, respiratory-related and non-respiratory-related) for pirfenidone and placebo patients over 12 months are summarised. Rate of death post-hospitalisation was also reported. Results A total of 1,247 patients (692 CAPACITY and 555 ASCEND) were included (Table). In pooled analyses, the proportion of patients experiencing ≥1 all-cause hospitalizations over 12 months was no different between pirfenidone and placebo-treated patients. The proportion of patients experiencing ≥1 respiratory-related hospitalizations was 12% in the placebo group vs 7% in the pirfenidone group (odds ratio 0.56; P = 0.004). Deaths after hospitalisation were numerically reduced in the pirfenidone group, most substantially for respiratory-related hospitalizations. Conclusion Patients with IPF frequently require hospitalisation for a variety of reasons. Pirfenidone may reduce the risk of non-elective respiratory-related hospitalizations over 12 months. Abstract P173 Table 1 Non-elective Hospitalizations in Patients Treated With Pirfenidone or Placebo over 12 Months All-Cause Hospitalizations Respiratory-Related Hospitalizations Non-Respiratory Hospitalizations Hospitalizations Pirfenidone(N = 623) Placebo(N = 624) Pirfenidone(N = 623) Placebo(N = 624) Pirfenidone(N = 623) Placebo(N = 624) Events, n 140 147 57 86 83 61 Patients with ≥1 event n (%) 106 (17) 112 (18) 44 (7) 74 (12) 68 (11) 51 (8) Odds ratio (95% CI) 0.94 (0.70, 1.26) 0.56 (0.38, 0.84) 1.38 (0.94, 2.02) P-value 0.662 0.004 0.099 Died after hospitalisation, n (%) 18 (17) 37 (33) 12 (27) 34 (46) 7 (10) 9 (18)