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Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

Noble PW, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Lancaster L, Lederer DJ, Leff JA, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, King TE - Eur. Respir. J. (2015)

Bottom Line: Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis.At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%).A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea.

View Article: PubMed Central - PubMed

Affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA Paul.Noble@cshs.org.

No MeSH data available.


Related in: MedlinePlus

a) Kaplan–Meier distribution of time to confirmed ≥10% decline in forced vital capacity (FVC) % predicted or death in the pooled population. b) Kaplan–Meier distribution of progression-free survival in the pooled population. Time to first occurrence of death or disease progression (confirmed >10% decline in FVC % pred or confirmed >50 m decrement in 6MWD). c) Kaplan–Meier distribution of time to confirmed ≥50 m decline in 6MWD or death in the pooled population. d) Kaplan–Meier distribution of time to worsening dyspnoea or death in the pooled population. Defined as a confirmed ≥20-point increase in UCSD SOBQ score or death. HR: hazard ratio; UCSD SOBQ: University of California San Diego Shortness of Breath Questionnaire (scale 0–120; higher scores indicate worse dyspnoea). #: Cox proportional hazards model; ¶: log-rank test. +: reported as the number of patients at risk on the last day of each 12-week study period in each study (excludes five patients from the pirfenidone group and six patients from the placebo group who had no post-randomisation follow-up assessment).
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Figure 6: a) Kaplan–Meier distribution of time to confirmed ≥10% decline in forced vital capacity (FVC) % predicted or death in the pooled population. b) Kaplan–Meier distribution of progression-free survival in the pooled population. Time to first occurrence of death or disease progression (confirmed >10% decline in FVC % pred or confirmed >50 m decrement in 6MWD). c) Kaplan–Meier distribution of time to confirmed ≥50 m decline in 6MWD or death in the pooled population. d) Kaplan–Meier distribution of time to worsening dyspnoea or death in the pooled population. Defined as a confirmed ≥20-point increase in UCSD SOBQ score or death. HR: hazard ratio; UCSD SOBQ: University of California San Diego Shortness of Breath Questionnaire (scale 0–120; higher scores indicate worse dyspnoea). #: Cox proportional hazards model; ¶: log-rank test. +: reported as the number of patients at risk on the last day of each 12-week study period in each study (excludes five patients from the pirfenidone group and six patients from the placebo group who had no post-randomisation follow-up assessment).

Mentions: Assessment of outcomes at the time of the study end-point in the respective studies showed that the magnitude of treatment effect following treatment for up to 72 weeks was generally consistent with the observed magnitude of effect at 1 year (figure 6). The risk of a ≥10% decline in FVC % pred or death was reduced by 52% (hazard ratio 0.48, 95% CI 0.37–0.63; p<0.001), the risk of death or disease progression was reduced by 38% (hazard ratio 0.62, 95% CI 0.52–0.75; p<0.001) and the risk of a ≥50 m decrement in 6MWD or death was reduced by 34% (hazard ratio 0.66, 95% CI 0.54–0.82; p<0.001) in the pirfenidone group compared with placebo. Dyspnoea outcomes suggested a more modest treatment benefit; at the time of the study primary end-point, there was a 25% reduction in the risk of worsening dyspnoea (as measured by a ≥20-point increase in UCSD SOBQ score) or death in the pirfenidone group compared with placebo (hazard ratio 0.75, 95% CI 0.60–0.93; p=0.007).FIGURE 6


Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

Noble PW, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Lancaster L, Lederer DJ, Leff JA, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, King TE - Eur. Respir. J. (2015)

a) Kaplan–Meier distribution of time to confirmed ≥10% decline in forced vital capacity (FVC) % predicted or death in the pooled population. b) Kaplan–Meier distribution of progression-free survival in the pooled population. Time to first occurrence of death or disease progression (confirmed >10% decline in FVC % pred or confirmed >50 m decrement in 6MWD). c) Kaplan–Meier distribution of time to confirmed ≥50 m decline in 6MWD or death in the pooled population. d) Kaplan–Meier distribution of time to worsening dyspnoea or death in the pooled population. Defined as a confirmed ≥20-point increase in UCSD SOBQ score or death. HR: hazard ratio; UCSD SOBQ: University of California San Diego Shortness of Breath Questionnaire (scale 0–120; higher scores indicate worse dyspnoea). #: Cox proportional hazards model; ¶: log-rank test. +: reported as the number of patients at risk on the last day of each 12-week study period in each study (excludes five patients from the pirfenidone group and six patients from the placebo group who had no post-randomisation follow-up assessment).
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Related In: Results  -  Collection

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Figure 6: a) Kaplan–Meier distribution of time to confirmed ≥10% decline in forced vital capacity (FVC) % predicted or death in the pooled population. b) Kaplan–Meier distribution of progression-free survival in the pooled population. Time to first occurrence of death or disease progression (confirmed >10% decline in FVC % pred or confirmed >50 m decrement in 6MWD). c) Kaplan–Meier distribution of time to confirmed ≥50 m decline in 6MWD or death in the pooled population. d) Kaplan–Meier distribution of time to worsening dyspnoea or death in the pooled population. Defined as a confirmed ≥20-point increase in UCSD SOBQ score or death. HR: hazard ratio; UCSD SOBQ: University of California San Diego Shortness of Breath Questionnaire (scale 0–120; higher scores indicate worse dyspnoea). #: Cox proportional hazards model; ¶: log-rank test. +: reported as the number of patients at risk on the last day of each 12-week study period in each study (excludes five patients from the pirfenidone group and six patients from the placebo group who had no post-randomisation follow-up assessment).
Mentions: Assessment of outcomes at the time of the study end-point in the respective studies showed that the magnitude of treatment effect following treatment for up to 72 weeks was generally consistent with the observed magnitude of effect at 1 year (figure 6). The risk of a ≥10% decline in FVC % pred or death was reduced by 52% (hazard ratio 0.48, 95% CI 0.37–0.63; p<0.001), the risk of death or disease progression was reduced by 38% (hazard ratio 0.62, 95% CI 0.52–0.75; p<0.001) and the risk of a ≥50 m decrement in 6MWD or death was reduced by 34% (hazard ratio 0.66, 95% CI 0.54–0.82; p<0.001) in the pirfenidone group compared with placebo. Dyspnoea outcomes suggested a more modest treatment benefit; at the time of the study primary end-point, there was a 25% reduction in the risk of worsening dyspnoea (as measured by a ≥20-point increase in UCSD SOBQ score) or death in the pirfenidone group compared with placebo (hazard ratio 0.75, 95% CI 0.60–0.93; p=0.007).FIGURE 6

Bottom Line: Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis.At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%).A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea.

View Article: PubMed Central - PubMed

Affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA Paul.Noble@cshs.org.

No MeSH data available.


Related in: MedlinePlus