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Treatment of idiopathic pulmonary fibrosis: a network meta-analysis

Treatment of idiopathic pulmonary fibrosis: a network meta-analysis
Treatment of idiopathic pulmonary fibrosis: a network meta-analysis

Background: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. Methods: We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (≥ 18years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). Results: A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. Conclusion: In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings.

Idiopathic pulmonary fibrosis, Network meta-analysis, Systematic review, Treatment
1741-7015
Rochwerg, Bram
20fff34b-de6c-4364-ab4e-33ea7d7319fc
Neupane, Binod
daeb36e7-2c76-4e59-9ad6-89837c4ddf0a
Zhang, Yuan
fd97400d-e191-40ca-a4ed-5d66c5a78144
Garcia, Carlos Cuello
955b437c-53fe-4d69-a49c-c6ae761bb985
Raghu, Ganesh
bf5d4a84-1eae-4e42-aac8-5fb9fb49d2ab
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Brozek, Jan
9735286c-65cd-4661-bb6c-c01a7b7b3573
Beyene, Joseph
c2f82336-3797-413d-87d6-585a84f371f1
Schünemann, Holger
d57a9844-6cfe-475f-b4a8-fd89104fee4c
Rochwerg, Bram
20fff34b-de6c-4364-ab4e-33ea7d7319fc
Neupane, Binod
daeb36e7-2c76-4e59-9ad6-89837c4ddf0a
Zhang, Yuan
fd97400d-e191-40ca-a4ed-5d66c5a78144
Garcia, Carlos Cuello
955b437c-53fe-4d69-a49c-c6ae761bb985
Raghu, Ganesh
bf5d4a84-1eae-4e42-aac8-5fb9fb49d2ab
Richeldi, Luca
47177d9c-731a-49a1-9cc6-4ac8f6bbbf26
Brozek, Jan
9735286c-65cd-4661-bb6c-c01a7b7b3573
Beyene, Joseph
c2f82336-3797-413d-87d6-585a84f371f1
Schünemann, Holger
d57a9844-6cfe-475f-b4a8-fd89104fee4c

Rochwerg, Bram, Neupane, Binod, Zhang, Yuan, Garcia, Carlos Cuello, Raghu, Ganesh, Richeldi, Luca, Brozek, Jan, Beyene, Joseph and Schünemann, Holger (2016) Treatment of idiopathic pulmonary fibrosis: a network meta-analysis. BMC Medicine, 14 (1), [18]. (doi:10.1186/s12916-016-0558-x).

Record type: Article

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. Methods: We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (≥ 18years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). Results: A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. Conclusion: In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings.

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More information

Accepted/In Press date: 15 January 2016
Published date: 3 February 2016
Keywords: Idiopathic pulmonary fibrosis, Network meta-analysis, Systematic review, Treatment

Identifiers

Local EPrints ID: 443450
URI: http://eprints.soton.ac.uk/id/eprint/443450
ISSN: 1741-7015
PURE UUID: a99c934f-2dcb-4449-ae03-536f1434377e

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Date deposited: 26 Aug 2020 16:34
Last modified: 07 Oct 2020 00:18

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