Restrictive allograft dysfunction after lung transplantation: is there a place for nintedanib?—a case report

Abstract

One of the posttransplantation complications is represented by chronic lung allograft dysfunction, which has two main clinical presentations: bronchiolitis obliterans syndrome and restrictive allograft syndrome. The latter being challenging because of poor prognosis and only symptomatic treatment, and characterized by fibrotic process. A 63‐year‐old man was right lung‐transplanted in 2009 due to idiopathic pulmonary fibrosis. In 2011, bronchiolitis obliterans syndrome was diagnosed evolving to restrictive allograft syndrome in 2016. An off‐label treatment by nintedanib (150 mg twice a day) was introduced. Unfortunately, it was stopped 4 months later because of digestive intolerance, without any clinical improvement. Contrary to a previous case reported, our patient did not have any benefit of nintedanib. Antifibrotic agents' effects such as nintedanib on restrictive allograft syndrome should be assessed in further randomized double‐blind placebo‐controlled studies.

Pleuroparenchymal Fibroelastosis and Serositis as Pleural Complications after Hematopoietic Stem Cell and Lung Transplantation

“…In the study by Nasser et al the decline in FVC was less in those that received nintedanib compared to placebo, however the upper lobe volume loss determined by CT measurements did not differ over time between groups [38,91]. In the case report by Pluchart et al regarding the use of nintedanib in a post-lung transplant patient, there was no clinical change after 4 months of treatment with treatment eventually discontinued due to adverse effects [95]. For pirfenidone, in the case report by Sato et al, their patient had stable pulmonary function tests after initiation of pirfenidone, however this patient had mixed PPFE and UIP, as confirmed by open lung biopsy, so it is unclear if the PPFE responded to pirfenidone or just the UIP [94].…”

“…Photophoresis therapy has been tried in lung transplant patients with RAS/PPFE but similar to other treatments described above has not been shown to be effective, although it may be helpful in those with strictly BOS [92,93]. Recently, use of nintedanib and pirfenidone has been described in a small series of patients with either idiopathic or secondary PPFE [37,91] and in case reports after lung transplant in those with RAS/PPFE [94,95]. In the study by Nasser et al the decline in FVC was less in those that received nintedanib compared to placebo, however the upper lobe volume loss determined by CT measurements did not differ over time between groups [38,91].…”

Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions

“…Preliminary data from a case series of 11 RAS patients showed that pirfenidone stabilised lung function during long-term treatment and provided a bridge to a second lung transplant in three patients (27%) [ 142 ]. Published data with nintedanib are limited to case reports: one showed a clinical benefit in a patient with BOS after HSCT [ 143 ], and another showed no benefit in a patient with BOS after lung transplantation [ 144 ].…”

Pharmacotherapy of chronic lung allograft dysfunction post lung transplantation

“…Antifibrotic therapies, pirfenidone and nintedanib, have also been investigated as a potential treatment modality for CLAD since its pathogenesis, especially the RAS phenotype, shares many similarities with idiopathic pulmonary fibrosis (IPF). These drugs are currently only FDA approved for the treatment of IPF and currently available evidence for CLAD is largely limited to case reports or case series that have shown stabilization or slowing rate of decline of pulmonary function after treatment with pirfenidone or nintendanib 60,61 . Vos et al.…”