BMJ Open Respiratory Research (Jun 2024)

Mycophenolate and azathioprine efficacy in interstitial lung disease: a systematic review and meta-analysis

  • ,
  • Sally Singh,
  • Mark Jones,
  • Michael Kreuter,
  • Maria Molina-Molina,
  • Imre Noth,
  • Andrew Wilson,
  • Martin Brutsche,
  • Naftali Kaminski,
  • Gary M Hunninghake,
  • Michael Keane,
  • Nazia Chaudhuri,
  • Ian Forrest,
  • Bruno Crestani,
  • Fernando J Martinez,
  • Mohsen Sadatsafavi,
  • Luca Richeldi,
  • Antje Prasse,
  • Fasihul Khan,
  • Iain Stewart,
  • Steve Jones,
  • Gisli Jenkins,
  • Gauri Saini,
  • David Turner,
  • Killian Hurley,
  • Lucilla Piccari,
  • Andrew Palmer,
  • Joseph A Lasky,
  • Simon Hart,
  • Joyce Lee,
  • Anthony Gordon,
  • John Blaikley,
  • Kirsty Hett,
  • Helmut Prosch,
  • Elisabeth Bendstrup,
  • Christopher Huntley,
  • Helen Parfrey,
  • Huzaifa Adamali,
  • Paul Beirne,
  • Stephen Bianchi,
  • George Chalmers,
  • Sophie Fletcher,
  • Peter George,
  • Michael Gibbons,
  • Mark Spears,
  • Laura Fabbri,
  • Felix Chua,
  • Michael Henry,
  • Cormac McCarthy,
  • Sabrina Paganoni,
  • Joseph Jacob,
  • Mark Toshner,
  • Bibek Gooptu,
  • Andrew Briggs,
  • Philip L Molyneaux,
  • Athol Wells,
  • Charlotte Summers,
  • Leticia Kawano-Dourado,
  • Ian Glaspole,
  • Melanie Quintana,
  • Christopher J Ryerson,
  • Paolo Spagnolo,
  • Francesco Bonella,
  • Carisi Anne Polanczyk,
  • Anjali Crawshaw,
  • Laurence Pearmain,
  • Avinash Anil Nair,
  • Raphaël Borie,
  • Alexandre Biasi Cavalcanti,
  • Emanuela Falaschetti,
  • Jonathan Chung,
  • James Eaden,
  • Kate Johnson,
  • Shaney Barratt,
  • Chris Ryerson,
  • Juergen Behr,
  • Andreas Guenther,
  • Nik Hirani,
  • Karin Storrer,
  • Deepak Talwar,
  • Claudia Ravaglia,
  • Katerina Antoniou,
  • Sara Freitas,
  • Carlo Vancheri,
  • Laura Price,
  • Amanda Goodwin,
  • Daniel Chambers,
  • Gunnar Gudmundsson,
  • Roger Lewis,
  • Ingrid Cox,
  • Anne Holland,
  • Erica Farrand,
  • Argyrios Tzouvelekis,
  • Rui Rolo,
  • Duncan Richards,
  • Larissa Schwarzkopf,
  • Sabina Guler,
  • Devesh Dhasmana,
  • Claudia Valenzuela,
  • John S Kim,
  • Louise Crowley,
  • Lisa Watson,
  • Amanda Bravery,
  • Elisabetta Balestro,
  • Wendy Adams,
  • Francesco Lombardi,
  • Ali Mojibian,
  • Ana Etges,
  • Ana Sousa Marcelino Boshoff,
  • Anne Bergeron Anna-MariaHoffmann-Vold,
  • Athina Trachalaki,
  • Barbara Wendelberger,
  • Bhavika Kaul Ben Hope-Gill,
  • Bruno Baldi,
  • Carlos Robalo,
  • Chris Grainge,
  • Christophe von Garnier,
  • Conal Hayton,
  • Dapeng Wang,
  • Daphne Bablis,
  • David Thicket,
  • Deji Adegunsoye,
  • Devaraj Anand,
  • Dhruv Parek,
  • Diane Griffiths,
  • Eliana Santucci,
  • Eliza Tsitoura,
  • Emma Karlsen,
  • Ena Gupta,
  • Harold Collard,
  • Hernan Fainberg,
  • Iazsmin Bauer-Ventura,
  • Irina Strambu,
  • Jacobo Sellares,
  • Janet Johnston,
  • Jeff Swigris,
  • Karina Negrelli,
  • Katarzyna Lewandowska,
  • Katrin Hostettler,
  • Kerri Johannson,
  • Liam Galvin,
  • Lisa G. Spencer,
  • Manuela Funke Chambour,
  • Marlies Wijsenbeek-Lourens,
  • Martina Vasakova,
  • Milena Man Iuliu Hatieganu,
  • Nick Weatherley,
  • Ovidiu Fira Mladinescu Victor Babes,
  • Peter Bryce,
  • Pilar Rivera Ortega,
  • Radu Crisan-Dabija,
  • Rahul Maida,
  • Sara Piciucchi,
  • Shama Malik,
  • Simone Dal Corso,
  • Stefan Stanel

DOI
https://doi.org/10.1136/bmjresp-2023-002163
Journal volume & issue
Vol. 11, no. 1

Abstract

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Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223.