Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Pitre, Tyler; Mah, Jasmine; Helmeczi, Wryan; Khalid, Faran; Cui, Sonya; Zhang, Melanie; Husnudinov, Renata; Su, Johnny; Banfield, Laura; Guy, Brent; Coyne, Jade; Scallan, Ciaran; Kolb, Martin; Jones, Aaron; Zeraatkar, Dena

doi:10.1136/thoraxjnl-2021-217976

Cited by 37 publications

(41 citation statements)

References 78 publications

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“…Two reviewers, working independently and in duplicate, assessed risk of bias using a revision of the Cochrane tool for assessing risk of bias in randomized trials (RoB 2.0) (12)(13)(14). For all outcome data that we extracted from eligible trials, we rated risk of bias as either at i) low risk of bias, ii) probably low risk of bias) iii) probably high risk of bias or iv) high risk of bias, across the following domains: bias arising from the randomization process; departures from the intended intervention; missing outcome data; measurement of the outcome; and selection of the reported results.…”

Section: Risks Of Biasmentioning

confidence: 99%

Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

Pitre

Mah

et al. 2022

Preprint

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Purpose Corticosteroids are standard of care for patients with severe COVID-19. However, the optimal dose is uncertain. We compare higher doses of corticosteroids with lower doses in patients with COVID-19. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, MedRxiv, and Web of Science from inception to January 7, 2022, for trials that randomized patients with severe-to-critical COVID-19 to corticosteroids, standard care, or placebo. Reviewers, working in duplicate, screened references, extracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. We performed a dose-response meta-analysis and used the GRADE framework to assess the certainty of evidence. We present our results in absolute risk difference (RD) per 1000 with 95% confidence intervals (CI). Results We included 19 trials, with 9,609 patients. We show that, compared to lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (RD 14.8 fewer deaths per 1000 [95% CI 6.0 to 27.9 fewer]; moderate certainty), may reduce the need for mechanical ventilation (RD 10.4 fewer per 1000 [95% CI 19.2 fewer to 3.6 more]; low certainty) and may reduce risk of nosocomial infections (16.7 fewer infections per 1000 [95% CI 5.4 to 25.0 fewer]; low certainty). Conclusions Relatively higher doses of corticosteroids may be beneficial in patients with severe-to-critical COVID-19 without increasing the risk of nosocomial infections.

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Section: Risks Of Biasmentioning

confidence: 99%

Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

Pitre

Mah

et al. 2022

Preprint

Self Cite

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“…Reviewers, working independently and in duplicate, assessed risk of bias using a revision of the Cochrane tool for assessing risk of bias in randomized trials (RoB 2.0). 13,14 We rated risk of bias as low, probably low, probably high or high, across the following domains: bias arising from the randomization process, departures from the intended intervention, missing outcome data, measurement of the outcome and selection of the reported results. We resolved discrepancies by discussion and, when ne cessary, with adjudication by a third party.…”

Section: Risks Of Biasmentioning

confidence: 99%

Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis

Pitre

Alstine

Chick

et al. 2022

CMAJ

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Most trials addressing the treatment of patients with COVID-19 have targeted patients admitted to hospital with severe or critical disease. 1 However, more recently, several treatments, including antiviral drugs, antidepressants, monoclonal anti bodies and inhaled corticosteroids, have been studied for patients with nonsevere COVID-19. 2 Preliminary evidence from ongoing or recently completed trials suggests that 2 novel antiviral drugsmolnupiravir and nirmatrelvir-ritonavir (Paxlovid) -may be effective at reducing risk of hospital admission. [3][4][5] To date, evidence on antiviral drugs for nonsevere COVID-19 has not been systematically synthesized or appraised. Furthermore, although efficacy data from trials of molnupiravir, nirmatrelvir-ritonavir and remdesivir are promising, no head-to-head trials have compared these drugs.A network meta-analysis allows for comparison of treatments that have not been compared in randomized controlled trials (RCTs), using pooled estimates from direct and indirect evidence.They can provide guidance to clinicians and evidence users in determining which treatments are superior. This is particularly important as health care systems attempt to prioritize access to effective COVID-19 treatments in the early stages of the disease.We sought to compare the effectiveness of antiviral drugs for patients with nonsevere COVID-19. MethodsWe conducted a systematic review and network meta-analysis, that included a rigorous appraisal of the evidence. We registered a protocol on Open Science Framework and uploaded the data used for this analysis (https://osf.io/zbcf9). We report our systematic review and network meta-analysis in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension statement for reporting of sys tematic reviews incorporating network meta-analyses. 6

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“…However, in idiopathic pulmonary fibrosis (IPF), the normal honeycomb structure of alveoli is replaced by fibrotic tissue, resulting in reduced gas exchange in early stages of the disease, which ultimately leads to death from pulmonary failure. IPF is essentially an intractable disease, although some headway has been made with antifibrotics: 5-year cumulative survival rates are 51.4% for people taking antifibrotics versus 43.9% for people not taking these drugs ( 1 ), and a 2.5%–4.3% reduction in the decline of forced viral capacity was reported across various antifibrotics in a recent meta-analysis ( 2 ). Even with current therapeutics, the prognosis for IPF patients is worse than for most cancers, including lung cancer.…”

Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis

Foster¹,

Tay²,

Oliver³

2022

Journal of Clinical Investigation

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Although aging and lung injury are linked to the development of idiopathic pulmonary fibrosis (IPF), the underlying pathognomonic processes predisposing to fibrotic lesions remain largely unknown. A deficiency in the ability of type 2 alveolar epithelial cell (AEC2) progenitors to regenerate and repair the epithelia has been proposed as a critical factor. In this issue of the JCI , Liang et al. identify a deficiency in the zinc transporter SLC39A8 (ZIP8) in AEC2s and in the subsequent activation of the sirtuin SIRT1 that predisposes to decreased AEC2 renewal capacity and enhanced lung fibrosis in both IPF and aging lungs. Interestingly, the authors demonstrate the efficacy of modulating dietary zinc levels, suggesting the need for clinical trials to evaluate the therapeutic potential of dietary supplementation and the development of pharmacological modulation of the Zn/ZIP8/SIRT1 axis for treatment.

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Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis

Cited by 37 publications

References 78 publications

Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

Antiviral drug treatment for nonsevere COVID-19: a systematic review and network meta-analysis

Deficiency in the zinc transporter ZIP8 impairs epithelia renewal and enhances lung fibrosis

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