Flora Charbonneau , Magali Dupuy-Grasset , Jeanne Languepin, Marie-Laure Laroche. Recognizing Arthralgia as a Potential Adverse Effect of CFTR Modulators: A Case Report Case Reports Clin Ther. 2026 Jan;48(1):117-120. doi: 10.1016/j.clinthera.2025.11.007. Epub 2025 Dec 5.PMID: 41353054
Free article. https://pubmed.ncbi.nlm.nih.gov/41353054/
Authors’ conclusions. Highly effective CFTRm represent a major therapeutic advancement for individuals with CF. Nonetheless, their full safety profile remains to be fully elucidated, particularly regarding potential effects on joint health. This case highlights that CFTRm can induce arthralgia, while also underscoring the complexity of managing this adverse event. Given the substantial clinical benefits of CFTRm, particularly in terms of pulmonary function and overall quality of life, discontinuation of therapy solely for the relief of joint pain is often not a viable option. This presents a therapeutic dilemma for both patients and clinicians. It is therefore essential that healthcare providers remain vigilant for the emergence or worsening of joint symptoms in patients whose disease is otherwise well controlled, as this may be an underrecognized adverse effect of CFTRm therapy. Early recognition and systematic reporting are crucial to improving understanding and guiding future management strategies. Full details in the free full article.
Flora Charbonneau is at the Regional Center of Pharmacovigilance, Department of Pharmacology, Toxiycology and Pharmacovigilance, Limoges’ University Hospital, Limoges, France
Sara Naimimohasses, Ankit Ray, Eunice Tan, Asher Wiggins , Bima J Hasjim, Shiyi Chen, Mamatha Bhat. Impact of Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapies on Liver Transplant Outcomes. Gastro Hep Adv 2025 Sep 14;5(2):100810. doi: 10.1016/j.gastha.2025.100810. eCollection 2026.https://pubmed.ncbi.nlm.nih.gov/41362828/
Sara Naimimohasses
University of Iowa Health
Background and aims: Up to 40% of patients with cystic fibrosis (CF) develop CF-related liver disease (CFrLD), which can progress to the point of requiring liver transplantation (LT). Advances in CF transmembrane conductance regulator (CFTR) modulator therapies, especially triple therapy modulators, have significantly improved pulmonary outcomes, but their impact on LT for CFrLD remains unclear.
Methods: Using data from the Scientific Registry of Transplant Recipients in 2000-2023, we analyzed trends in LT waitlisting for CFrLD pre- and post-U.S. Food and Drug Administration (FDA) approval of CFTR modulators: ivacaftor (January 31, 2012; single therapy), ivacaftor-lumacaftor (July 2, 2015; dual therapy), and ivacaftor-tezacaftor-elexacaftor (October 21, 2019; triple therapy). We compared the waitlist characteristics and post-LT outcomes of pre- and post-FDA approval eras.
Results: Of 258,090 patients waitlisted for LT, 551 (0.2%) had CFrLD. The proportion of CFrLD patients on the LT waitlist decreased after FDA approval of triple CFTR modulators (0.23% to 0.14%; P < .0004). Patients waitlisted after FDA approval of single and dual CFTR modulators were, on average, older (17.4 vs 20.6 years; P < .001 and 18.0 vs 20.8 years; P = .004). Median model for end-stage liver disease-sodium scores were higher among individuals waitlisted following the approval of dual (9 [6-14] vs 10 [8-15], P < .013) and triple (9 [6-14] vs 12.5 [8-17], P < .003) CFTR modulators. There were no significant differences in post-LT survival pre- and post-FDA approval of single, dual, or triple CFTR therapy.
Conclusion: These findings suggest that CFTR modulators may mitigate CFrLD complications and delay the need for waitlisting as physicians await the patient’s response to therapy and reassess the need for LT.
Sara Naimimohasses is at the Ajmera Transplant Centre, University Health Network, University of Toronto, Toronto, Canada.