Abstract
Introduction No proven treatments exist for bronchiolitis obliterans syndrome (BOS) following lung transplantation. Inhaled liposomal cyclosporine (L-CsA) may prevent BOS progression.
Methods A 48-week phase IIb randomised clinical trial was conducted in 21 lung transplant patients with BOS assigned to either L-CsA with standard-of-care (SOC) oral immunosuppression (L-CsA group) or SOC (SOC-alone group). Efficacy end-points were BOS progression-free survival (defined as absence of ≥20% decline in forced expiratory volume in 1 s (FEV1) from randomisation, re-transplantation or death) and BOS grade change.
Results BOS progression-free survival was 82% for L-CsA versus 50% for SOC-alone (p=0.1) and BOS grade worsened in 18% for L-CsA versus 60% for SOC-alone (p=0.05). Mean changes in ΔFEV1 and forced vital capacity, respectively, stabilised with L-CsA: +0.005 (95% CI −0.004– +0.013) and −0.005 (95% CI −0.015– +0.006) L·month−1, but worsened with SOC-alone: −0.023 (95% CI −0.033– −0.013) and −0.026 (95% CI −0.039– −0.014) L·month−1 (p<0.0001 and p=0.009). Median survival (4.1 versus 2.9 years; p=0.03) and infection rate (45% versus 60%; p=0.7) improved with L-CsA versus SOC-alone; creatinine and tacrolimus levels were similar.
Conclusions L-CsA was well tolerated and stabilised lung function in lung transplant recipients affected by BOS without systemic toxicity, providing a basis for a global phase III trial using L-CsA.
Abstract
Liposomal aerosol cyclosporine (L-CsA) was well tolerated and stabilised lung function in lung transplant recipients affected by BOS. The data provide evidence for an ongoing global phase III trial using L-CsA for BOS. http://bit.ly/2HB8w5j
Footnotes
This article has supplementary material available from openres.ersjournals.com
This study is registered at ClinicalTrials.gov with identifier number NCT01650545. Individual participant data will be available after de-identification, including the study protocol, within the first year after article publication. Investigators who propose to use the data will need to be approved by an independent review committee identified for this purpose, for individual participant data for meta-analyses. Proposals may be submitted up to 24 months following article publication.
Author contributions: A. Iacono, B Griffith and M. Terrin contributed to the conception and design of this study, interpreted results, and performed or assisted with the writing and the final proofing of the article to completion. I. Timofte, K. Rajagopal, M. Wijesinha and N. Murdock formulated specific databases for data interpretation, performed the final statistical analyses and commented on all study results formally, and also revised the manuscript critically for essential intellectual content. All authors gave final approval of the manuscript to be published, and agree to be accountable for data integrity and all other essential aspects.
Support statement: We are grateful to PARI Pharma GmbH for drug and device supply for this investigation, and a research grant to the University of Maryland School of Medicine; the IPF Foundation for nursing support; and the Plylar and Riehl Foundations for generously supporting the Lung Healing Center for overall study support. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: A. Iacono reports grants from PARI Pharmaceutical outside the submitted work. In addition, he has a patent for the “Use of Aerosolized Cyclosporine for Prevention and Treatment of Pulmonary Disease” issued and is Chairman for an upcoming phase III trial “Inhaled Liposomal Cyclosporine A (L-CsA) for the treatment of Bronchiolitis Obliterans (BO)”.
Conflict of interest: M. Wijesinha has nothing to disclose.
Conflict of interest: K. Rajagopal has nothing to disclose.
Conflict of interest: N. Murdock has nothing to disclose.
Conflict of interest: I. Timofte has nothing to disclose.
Conflict of interest: B. Griffith has nothing to disclose.
Conflict of interest: M. Terrin has nothing to disclose.
- Received July 2, 2019.
- Accepted August 25, 2019.
- Copyright ©ERS 2019
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
