A rare case of antifibrotic therapy in a patient with fibrotic pulmonary sarcoidosis

Sarcoidosis is a systemic inflammatory disease of unknown origin that can progress to fibrocavernous disease. Published data on antifibrotic therapy for fibrotic sarcoidosis are contradictory, largely due to an insufficient number of studies. In randomized trials, nintedanib has demonstrated efficacy in reducing the progression of interstitial lung disease; however, it has not shown a positive effect specifically in fibrotic sarcoidosis. Some individual studies have reported beneficial effects of antifibrotic therapy in cases of fibrotic sarcoidosis. Due to the limited and conflicting data, each observation of antifibrotic therapy in fibrotic sarcoidosis is valuable.

The aim. Here, we describe our experience of using antifibrotic therapy in a patient with fibrotic pulmonary sarcoidosis.

Methods. The patient, a 66-year-old woman with sarcoidosis-associated pulmonary fibrosis, has been receiving antifibrotic therapy (nintedanib 150 mg twice daily) since October 2022. Efficacy and safety were assessed before initiation and after 12, 24 and 32 months of antifibrotic therapy.

Results. The respiratory deterioration slowed down, evidenced by an increased distance in the 6-minute walk test. Pulmonary function decline was also reduced, with no decrease in FEV₁, FVC, FRC, or RV. Computed tomography scans revealed no progression in the volume of pulmonary fibrosis.

Conclusion. The use of antifibrotic therapy was associated with stabilization of pulmonary function and no progression of pulmonary fibrosis. Further studies on antifibrotic therapy in fibrotic sarcoidosis are warranted.

1. Bonham C.A., Strek M.E., Patterson K.C. From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis. Curr. Opin. Pulm. Med. 2016; 22 (5): 484–491. DOI: 10.1097/MCP.0000000000000301.

2. Kouranos V., Jacob J., Wells A.U. Severe sarcoidosis. Clin. Chest Med. 2015; 36 (4): 715–726. DOI: 10.1016/j.ccm.2015.08.012.

3. Valeyre D., Prasse A., Nunes H. et al. Sarcoidosis. Lancet. 2014; 383 (9923): 1155–1167. DOI: 10.1016/S0140-6736(13)60680-7.

4. Korsten P., Strohmayer K., Baughman R.P., Sweiss N.J. Refractory pulmonary sarcoidosis – proposal of a definition and recommendations for the diagnostic and therapeutic approach. Clin. Pulm. Med. 2016; 23 (2): 67–75. DOI: 10.1097/CPM.0000000000000136.

5. Lockstone H.E., Sanderson S., Kulakova N. et al. Gene set analysis of lung samples provides insight into pathogenesis of progressive, fibrotic pulmonary sarcoidosis. Am. J. Respir. Crit. Care Med. 2010; 181 (12): 136775. DOI: 10.1164/rccm.200912-1855OC.

6. Grunewald J., Kaiser Y., Ostadkarampour M. et al. T-cell receptor-HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis. Eur. Respir. J. 2016; 47 (3): 898–909. DOI: 10.1183/13993003.01209-2015.

7. Patterson K.C., Strek M.E. Pulmonary fibrosis in sarcoidosis. Clinical features and outcomes. Ann. Am. Thorac. Soc. 2013; 10 (4): 362–370. DOI: 10.1513/AnnalsATS.201303-069FR.

8. Desai S.R., Sivarasan N., Johannson, K.A. et al. High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study. Lancet Respir. Med. 2024; 12 (5): 409–418. DOI: 10.1016/S2213-2600(23)00267-9.

9. Vizel A.A., Avdeev S.N., Vizel I.Yu., Shakirova G.R. Sarcoidosis phenotyping: analysis of current approaches (review). Tuberc. Lung Dis. 2024; 102 (3): 84–94. DOI: 10.58838/2075-1230-2024-102-3-84-94.

10. Rosen Y. Pathology of sarcoidosis. Semin. Respir. Crit. Care Med. 2007; 28 (1): 36–52. DOI: 10.1055/s-2007-970332.

11. Flaherty K.R., Wells A.U., Cottin V. et al. Nintedanib in progressive fibrosing interstitial lung diseases. N. Engl. J. Med. 2019; 381 (18): 1718–1727. DOI: 10.1056/NEJMoa1908681.

12. Ghazipura M., Mammen M.J., Herman D.D. et al. Nintedanib in progressive pulmonary fibrosis: a systematic review and meta-analysis. Ann. Am. Thorac. Soc. 2022; 19 (6): 1040–1049. DOI: 10.1513/AnnalsATS.202103-343OC.

13. Comes A., Sofia C., Richeldi L. Novel insights in fibrotic pulmonary sarcoidosis. Curr. Opin. Pulm. Med. 2022; 28 (5): 478–484. DOI: 10.1097/MCP.0000000000000893.

14. Raghu G., Remy-Jardin M., Richeldi L. et al. Idiopathic pulmonary fibrosis (an update) and progressive pulmonary fibrosis in adults: An official ATS/ERS/JRS/ALAT clinical practice guideline. Am. J. Respir. Crit. Care Med. 2022; 205 (9): e18–47. DOI: 10.1164/rccm.202202-0399ST.

15. Chuchalin A.G., Avdeev S.N., Aisanov Z.R. et al. [Sarcoidosis: federal clinical guidelines for diagnosis and treatment]. Pul'monologiya. 2022; 32 (6): 806–833. DOI: 10.18093/0869-0189-2022-32-6-806-833 (in Russian).

16. Judson M.A. Antifibrotic drugs for pulmonary sarcoidosis: a treatment in search of an indication. Respir. Med. 2021; 180: 106371. DOI: 10.1016/j.rmed.2021.106371.

17. Nunes H., Brillet P.Y., Bernaudin J.F. et al. Fibrotic pulmonary sarcoidosis. Clin. Chest Med. 2024; 45 (1): 199–212. DOI: 10.1016/j.ccm.2023.08.011.