W Chou

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.

M32 Effect of pirfenidone on all-cause mortality (acm) and forced vital capacity (fvc) in idiopathic pulmonary fibrosis (ipf) patients with low fvc and/or low dlco: analysis of pooled data from ascend and capacity

Introduction The pivotal trials of the two approved therapies in IPF, pirfenidone and nintedanib, assessed patients with protocol-defined mild to moderate disease. The effect of pirfenidone in patients with more severe lung function impairment warrants further investigation. Pooled Results from ASCEND and CAPACITY studies (NCT01366209, NCT00287729 and NCT00287716) showed a significant reduction at 12 months in the risk of ACM (hazard ratio [HR], 0.52; 95% CI, 0.31, 0.87)1 and in decline of percent predicted FVC (%FVC; 14.8% vs. 26.3% patients with ≥10% decline in%FVC or death, p<0.0001)2 for patients treated with pirfenidone vs. placebo. We present pooled subgroup analyses from ASCEND and CAPACITY for patients with low baseline%FVC (<50%) and/or low percent predicted diffusing capacity for carbon monoxide (%DLCO <35%) to further inform on treatment effect of pirfenidone in patients with more severe lung function impairment. Methods ACM was compared using the log-rank test, and HR was estimated using Cox regression. The categorical change in%FVC was summarised with the percent of patients with a≥10% absolute decline or death, and treatment comparison was performed using the rank ANCOVA method. Annual rate of FVC decline was estimated using the mixed-effects model. Results 170 patients (90 pirfenidone, 80 placebo) had low%DLCO (n=157) or%FVC (n=13) at baseline. Treatment with pirfenidone was associated with a 72% reduction in risk of ACM over 12 months vs. placebo (4 vs. 12 deaths; HR, 0.28; 95% CI, 0.09, 0.86; p=0.018; Table). There was a 56% relative reduction in the proportion of patients with a ³10% absolute decline in%FVC or death at 12 months vs. placebo (18.9% vs. 42.5%; p=0.0038). The annual rates of FVC decline were 150 and 278 mL in the pirfenidone and placebo arms, respectively (p=0.003). Conclusions Treatment with pirfenidone resulted in clinically meaningful benefits for ACM and FVC decline in patients with baseline%FVC <50% and/or%DLCO <35%. These data suggest that patients with more severe lung function impairment can also benefit from pirfenidone therapy. References . King TE Jr, et al. N Engl J Med2014;370:2083–2092. . Noble PW, et al. Eur Resp J2016;47:27–30. Abstract M32 Table 1 ACM and FVC outcomes at 12 months in patients with IPF with low FVC and/or low DLCO at baseline* Endpoint at 12 Months Patients With Low FVC and/or Low DLCO (n=170) All Patients (n=1247) Pirfenidone vs placeboACM: HR (95% CI) 0.28 (0.09–0.86) 0.52 (0.31–0.87) Pirfenidone vs. placebo:≥10% absolute decline in%FVC or death 18.9% vs. 42.5%(p=0.0038) 14.8% vs. 26.3%(p<0.0001) Pirfenidone vs. placebo:Annual rate of FVC decline, mL 150 vs. 278(p=0.003) 109 vs. 208(p<0.0001) *All pirfenidone-treated patients included in these analyses were randomised to receive 2403 mg/day.

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)