Systematic Review and Network Meta-analysis of Idiopathic Pulmonary Fibrosis Treatments

Abstract

Fleetwood is an employee of Quantics Consulting. McCool and Glanville are employees of York Health Economics Consortium (YHEC). Quantics and YHEC received funding from F. Hoffmann-La Roche for conducting the systematic review and network meta-analysis reported in this paper. Edwards, Gsteiger, and Daigl are employees of F. Hoffmann-La Roche. Fisher was employed by InterMune UK, a wholly owned Roche subsidiary, until July 2015. He is currently employed by FIECON, which has received funding from F. Hoffmann-La Roche for consulting services. The systematic review and network meta-analysis reported in this paper were conducted by Fleetwood (Quantics Consulting) and McCool and Glanville (YHEC), funded by F. Hoffmann-La Roche. The original network analysis was funded by InterMune. Study concept and design were contributed by Edwards, Gsteiger, and Daigl, along with Fleetwood, McCool, and Glanville. Fleetwood, McCool, and Glanville collected the data, with assistance from Edwards, Gsteiger, and Daigl. Data interpretation was performed by Fleetwood and Fisher, with assistance from the other authors. The manuscript was written by Fleetwood, McCool, and Glanville, with assistance from Edwards, Daigl, and Fisher, and revised by all the authors.

Leucine-rich α -2 glycoprotein promotes lung fibrosis by modulating TGF-β signaling in fibroblasts

“…Although there is evidence that these drugs successfully slow the decline in forced vital capacity over a year (Fleetwood et al. ), the therapeutic responses differ between individuals (Loeh et al. ), and the effectiveness of antifibrotic therapies remain limited.…”

“…Nintedanib is a small molecule that inhibits the activity of tyrosine kinase receptors, such as vascular endothelial growth factor (VEGF) receptor, PDGF receptor, and FGF receptor (Wollin et al 2014). Although there is evidence that these drugs successfully slow the decline in forced vital capacity over a year (Fleetwood et al 2017), the therapeutic responses differ between individuals (Loeh et al 2015), and the effectiveness of antifibrotic therapies remain limited. Therefore, it would be useful to elucidate the molecular mechanism of fibrosis in IPF to identify new potential targets for treatment of this disease.…”

Pathogenetic significance and possibility as a therapeutic target of platelet derived growth factor

“…The recombinant human variant of PDGF‐BB, Becaplermin, is the only growth factor approved by FDA that has been applied against intractable ulcers . PDGF is supposed to be invovled in lung fibrosis 81 , and nintedanib, a kinase inhibitor for several kinases including PDGFR, was approved for idiopathic pulmonary fibrosis in worldwide . Recent data have unraveled that the mutations of PDGFRB are etiologically related to diseases with systemic connective tissue abnormalities.…”

Análise de custo-efetividade de pirfenidona em comparação a nintedanibe no tratamento de fibrose pulmonar idiopática na perspectiva do sistema suplementar de saúde brasileiro

“…Na ausência de dados de comparação direta (head-to-head) para avaliação de pirferidona e de nintedanibe, uma comparação indireta realizada por revisão sistemática e metanálise em rede Bayesiana (NMA, do inglês network meta-analysis) foi utilizada para os dados clínicos de eficácia (Fleetwood et al, 2017). A revisão sistemática foi conduzida até abril de 2015 e os ensaios clínicos elegíveis foram os randomizados de fase II/III para pacientes adultos com FPI.…”

“…Para a obtenção de ambas as curvas de Kaplan-Meier (KM) utilizadas no modelo, aplicaram-se os HRs obtidos no NMA (Fleetwood et al, 2017) às curvas de sobrevida global e sobrevida livre de progressão dos estudos de pirfenidona (CAPACITY e ASCEND) Noble et al, 2011). Para a definição da extrapolação da curvas de sobrevida global, baseadas nas curvas de KM, uma distribuição paramétri-ca Weibull foi escolhida (Figura 2).…”