Association Between FEV1 Decline Rate and Mortality in Long-Term Follow-Up of a 21-Patient Pilot Clinical Trial of Inhaled Liposomal Cyclosporine Plus Standard-of-Care Versus Standard-of-Care Alone for Bronchiolitis Obliterans Syndrome After Lung Transplantation.
Iacono, A., et al.Annals of Transplantation 2024; 29: e942823.
Aims
To assess the longer-term association between FEV trajectory and mortality in a clinical trial cohort who received inhaled liposomal cyclosporin (L-CsA-I) or standard of care (SoC) for bronchiolitis obliterans syndrome (BOS).
Interventions
The intervention within the original trial was upon diagnosis of BOS recipients were randomised to SoC alone or SoC with 24 weeks of twice daily L-CsA-I.
Participants
21 adult lung transplant recipients (10 single & 11 double lung recipients).
Outcomes
The primary aim of the secondary analysis is to assess if longitudinal changes of FEV1 could be used as a predictor of mortality. Secondary outcomes: FEV1 changes between L-CsA-I and SOC patients beyond the initial trial interval formally reported, Progression to subsequent BOS grade, survival duration and cause of death.
Follow-up
Median of 35 months (up to 7.5 years) from original randomisation.
CET Conclusions
This is a secondary analysis of prolonged follow-up data from a single centre open-label randomised clinical trial of L-CsA-I in BOS published in 2019, with an impressive median follow-up of 35 months and up to 90 months. The initial trial was a small single centre study containing 21 participants, as such there is insufficient power for this post-hoc analysis. They aim to assess, and thus provide some potential validation for FEV trajectory as a potential predictor of mortality in BOS. They found for every 1% decline in FEV was predicted to increase the risk of death by 7.6%, however this was not significant, p=0.058. There is a parallel with Todd et al’s large retrospective analysis of over 200 patients in which lower absolute FEV in BOS and restrictive chronic allograft dysfunction is associated with increase mortality, but here in this small, exclusive BOS population an attempt to look at longitudinal changes in FEV causing increase mortality risk is made. Given they are assessing early FEV and mortality in a cohort in which some received novel treatment, assessment of time-by-treatment interaction is required, with a non-significant (p=0.2) potential protective effect on L-CsA-I in preserving 2.6% per year of FEV. Conceptually the secondary analysis is good, and utilising trial cohorts for validation of predictors in unique populations such as those with BOS is valid, however the small sample size has limited the present analysis such that no clear conclusions can be made on this cohort. Powering a subsequent multicentre trial of this potentially beneficial treatment for a post-hoc analysis of potential predictors would be of importance.
Trial registration
ClinicalTrials.gov - NCT01650545