Why don’t anti-inflammatories work in cystic fibrosis?

Figures & data

Table 1. Summary of discussed anti-inflammatory therapies investigated in CF.

Drug class or therapeutic target	Drug evaluated	Clinical outcome	Impact on inflammatory mediators	Clinical studies (references)
Corticosteroids	Prednisolone	Slowed FEV1 decline in children	Reduced systemic inflammatory mediators	[5]
		No significant improvement in clinical outcomes assessed in adult patients treated during pulmonary exacerbation versus those treated with antibiotics alone	No difference in C-reactive protein measured between groups	[15]
Antibiotic	Azithromycin	Reduced pulmonary exacerbation frequency Improved FEV1 in P.aeruginosa infected patients	No significant impact on airway inflammatory mediators measured	[10,11]
Non-steroidal anti-inflammatory drugs	Ibuprofen	Slowed FEV1 decline	Not reported	[8,9]
Leukotriene pathway inhibition	BIIL 284 BS (LTB4 receptor antagonist)	Terminated early due to adverse events	Not reported	[6]
	Acebilustat (LTA4 hydrolase inhibitor)	No significant improvement in clinical outcomes at week 48	No significant impact on inflammatory mediators measured	[14]
Cannabinoid receptor type 2 agonist	Lenabasum	No significant improvement in clinical outcomes at week 12	Reduction in airway inflammatory mediators	[12]
CFTR modulator drugs	Elexacaftor/Tezacaftor/Ivacaftor	Improved FEV1 Reduced pulmonary exacerbation frequency Increased weight	Reduced systemic and airway inflammatory mediators	[3,4]

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Konstan MW, VanDevanter DR, Sawicki GS, et al. Association of high-dose ibuprofen use, lung function decline, and long-term survival in children with cystic fibrosis. Ann Am Thorac Soc. 2018;15(4):485–493. doi: 10.1513/AnnalsATS.201706-486OC

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Konstan MW, Byard PJ, Hoppel CL, et al. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995;332(13):848–854. doi: 10.1056/NEJM199503303321303

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Konstan MW, Döring G, Heltshe SL, et al. A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis. J Cyst Fibros. 2014;13(2):148–155. doi: 10.1016/j.jcf.2013.12.009

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Elborn JS, Konstan MW, Taylor-Cousar JL, et al. Empire-CF study: a phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis. J Cyst Fibros. 2021;20(6):1026–1034. doi: 10.1016/j.jcf.2021.08.007

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Chmiel JF, Flume P, Downey DG, et al. Safety and efficacy of lenabasum in a phase 2 randomized, placebo-controlled trial in adults with cystic fibrosis. J Cyst Fibros. 2021;20(1):78–85. doi: 10.1016/j.jcf.2020.09.008

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Schaupp L, Addante A, Völler M, et al. Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on sputum viscoelastic properties, airway infection and inflammation in patients with cystic fibrosis. Eur Respir J. 2023;62(2):2202153. doi: 10.1183/13993003.02153-2022

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Casey M, Gabillard-Lefort C, McElvaney OF, et al. Effect of elexacaftor/tezacaftor/ivacaftor on airway and systemic inflammation in cystic fibrosis. Thorax. 2023;78(8):835–839. doi: 10.1136/thorax-2022-219943

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