A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation

Abstract

IntroductionNo proven treatments exist for bronchiolitis obliterans syndrome (BOS) following lung transplantation. Inhaled liposomal cyclosporine (L-CsA) may prevent BOS progression.MethodsA 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.ResultsBOS progression-free survival was 82% for L-CsAversus50% for SOC-alone (p=0.1) and BOS grade worsened in 18% for L-CsAversus60% for SOC-alone (p=0.05). Mean changes in ΔFEV1and 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 (4.1versus2.9 years; p=0.03) and infection rate (45%versus60%; p=0.7) improved with L-CsAversusSOC-alone; creatinine and tacrolimus levels were similar.ConclusionsL-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.