Enhancing Outcomes in Chronic Fibrotic Interstitial Lung Disease Through Aggressive Management of Nintedanib-Induced Adverse Drug Reactions: A Retrospective Analysis. - National Genomics Data Center (CNCB-NGDC)

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Enhancing Outcomes in Chronic Fibrotic Interstitial Lung Disease Through Aggressive Management of Nintedanib-Induced Adverse Drug Reactions: A Retrospective Analysis.

Yu-Wen Chang, Meng-Yun Tsai, Yu-Ping Chang, Chien-Chang Liao, Yu-Ting Lin, Chien-Hao Lai, Meng-Chih Lin, Kuo-Tung Huang

Author Information

Yu-Wen Chang: Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Meng-Yun Tsai: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan, ROC.
Yu-Ping Chang: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan, ROC.
Chien-Chang Liao: Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Yu-Ting Lin: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chien-Hao Lai: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan, ROC.
Meng-Chih Lin: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan, ROC.
Kuo-Tung Huang: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung, Taiwan, ROC. jelly@cgmh.org.tw. ORCID

PMID: 39102100 DOI: 10.1007/s40801-024-00443-0

BACKGROUND AND OBJECTIVES: Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes.
METHODS: This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed.
RESULTS: The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016).
CONCLUSION: Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Travis WD, Costabel U, Hansell DM, King TE Jr, Lynch DA, Nicholson AG, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–48. [DOI: 10.1164/rccm.201308-1483ST]

Cottin V, Wollin L, Fischer A, Quaresma M, Stowasser S, Harari S. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019;28(151):180100.

Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–82. [DOI: 10.1056/NEJMoa1402584]

Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med. 2016;113:74–9. [DOI: 10.1016/j.rmed.2016.02.001]

Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, et al. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: Results from the TOMORROW trial and its open-label extension. Thorax. 2018;73(6):581–3. [DOI: 10.1136/thoraxjnl-2016-209701]

Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011;365(12):1079–87. [DOI: 10.1056/NEJMoa1103690]

Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019;380(26):2518–28. [DOI: 10.1056/NEJMoa1903076]

Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019;381(18):1718–27. [DOI: 10.1056/NEJMoa1908681]

Crestani B, Huggins JT, Kaye M, Costabel U, Glaspole I, Ogura T, et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. Lancet Respir Med. 2019;7(1):60–8. [DOI: 10.1016/S2213-2600(18)30339-4]

US Food & Drug Administration, label OFEV (nintedanib). September 2019. Reference ID 4572087.

Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, Lee JS, Maher TM, Wells AU, Antoniou KM, Behr J, Brown KK, Cottin V, Flaherty KR, Fukuoka J, Hansell DM, Johkoh T, Kaminski N, Kim DS, Kolb M, Lynch DA, Myers JL, Raghu G, Richeldi L, Taniguchi H, Martinez FJ. Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report. Am J Respir Crit Care Med. 2016;194(3):265–75. [DOI: 10.1164/rccm.201604-0801CI]

Luppi F, Sebastiani M, Salvarani C, Bendstrup E, Manfredi A. Acute exacerbation of interstitial lung disease associated with rheumatic disease. Nat Rev Rheumatol. 2022;18(2):85–96. [DOI: 10.1038/s41584-021-00721-z]

Song JW, Ogura T, Inoue Y, Xu Z, Quaresma M, Stowasser S, et al. Long-term treatment with nintedanib in Asian patients with idiopathic pulmonary fibrosis: Results from INPULSIS®-ON. Respirology. 2020;25(4):410–6. [DOI: 10.1111/resp.13647]

Cheng SL, Sheu CC, Chian CF, Hsu JY, Kao KC, Hang LW, et al. NICEFIT–A prospective, non-interventional, and multicentric study for the management of idiopathic pulmonary fibrosis with antifibrotic therapy in Taiwan. Biomedicines. 2022;10(10):2362.

Ogura T, Inoue Y, Azuma A, Homma S, Kondoh Y, Tanaka K, et al. Real-world safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: Interim report of a post-marketing surveillance in Japan. Adv Ther. 2023;40(4):1474–93. [DOI: 10.1007/s12325-022-02411-y]

Kato M, Sasaki S, Tateyama M, Arai Y, Motomura H, Sumiyoshi I, et al. Clinical significance of continuable treatment with nintedanib over 12 months for idiopathic pulmonary fibrosis in a real-world setting. Drug Des Devel Ther. 2021;15:223–30. [DOI: 10.2147/DDDT.S284819]

Yoon HY, Park S, Kim DS, Song JW. Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis. Respir Res. 2018;19(1):203. [DOI: 10.1186/s12931-018-0907-8]

Dobashi M, Tanaka H, Taima K, Itoga M, Ishioka Y, Shiratori T, et al. The efficacy of nintedanib in 158 patients with idiopathic pulmonary fibrosis in real-world settings: a multicenter retrospective study. SAGE Open Med. 2021;9:20503121211023356. [DOI: 10.1177/20503121211023357]

Toellner H, Hughes G, Beswick W, Crooks MG, Donaldson C, Forrest I, et al. Early clinical experiences with nintedanib in three UK tertiary interstitial lung disease centres. Clin Transl Med. 2017;6(1):41. [DOI: 10.1186/s40169-017-0172-3]

Antoniou K, Markopoulou K, Tzouvelekis A, Trachalaki A, Vasarmidi E, Organtzis J, et al. Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: a retrospective, observational, cohort study. ERJ Open Res. 2020;6(1):00172–2019.

Bonella F, Kreuter M, Hagmeyer L, Neurohr C, Keller C, Kohlhaeufl MJ, et al. Insights from the German compassionate use program of nintedanib for the treatment of idiopathic pulmonary fibrosis. Respiration. 2016;92(2):98–106. [DOI: 10.1159/000448288]

Galli JA, Pandya A, Vega-Olivo M, Dass C, Zhao H, Criner GJ. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions. Respirology. 2017;22(6):1171–8. [DOI: 10.1111/resp.13024]

Tzouvelekis A, Karampitsakos T, Kontou M, Granitsas A, Malliou I, Anagnostopoulos A, et al. Safety and efficacy of nintedanib in idiopathic pulmonary fibrosis: a real-life observational study in Greece. Pulm Pharmacol Ther. 2018;49:61–6. [DOI: 10.1016/j.pupt.2018.01.006]

Fletcher SV, Jones MG, Renzoni EA, Parfrey H, Hoyles RK, Spinks K, et al. Safety and tolerability of nintedanib for the treatment of idiopathic pulmonary fibrosis in routine UK clinical practice. ERJ Open Res. 2018;4(4):00049–2018.

Huang TH, Kuo CW, Chen CW, Tseng YL, Wu CL, Lin SH. Baseline plasma KL-6 level predicts adverse outcomes in patients with idiopathic pulmonary fibrosis receiving nintedanib: a retrospective real-world cohort study. BMC Pulm Med. 2021;21(1):165. [DOI: 10.1186/s12890-021-01530-6]

Tseng CM, Chen MY, Kao CY, Tao CW. Investigation of clinical predictors of survival in idiopathic pulmonary fibrosis patients: a cohort study in Taiwan. J Chin Med Assoc. 2022;85(5):578–83. [DOI: 10.1097/JCMA.0000000000000719]

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