Evidence-based interventions for nintedanib-induced diarrhea in patients with pulmonary fibrosis

CAT | 2023

Introduction: Drug-induced diarrhea accounts for approximately 7% of all drug-related side effects. Although it is primarily self-limiting, severe cases of diarrhea can pose life-threatening risks. This treatment-related diarrhea is a significant challenge for patients with pulmonary fibrosis (PF) undergoing treatment with nintedanib, a currently prescribed multitargeted tyrosine kinase inhibitor (TK). Approximately 62-76% of patients using nintedanib experience diarrhea as an adverse effect of this treatment. In certain cases, patients are compelled to discontinue treatment because of the onset of diarrhea as a side effect. However, there are limited pharmaceutical alternatives available for patients with PF. Therefore, effective management of nintedanib-induced diarrhea is critical. Currently, diarrhea resulting from nintedanib usage is addressed with antidiarrheal medications, such as loperamide. However, this approach can be suboptimal and lacks a solid evidence base for effective management of nintedanib-induced diarrhea. There are limited alternative strategies in use, and a consensus on the best approach for managing this type of diarrhea is lacking. Furthermore, there are no guidelines to provide a clear direction for treating nintedanib-induced diarrhea.
Methods: This critically appraised topic (CAT) investigated the existence of evidence-based interventions for suppressing diarrhea associated with nintedanib. Both pharmacological and non-pharmacological options were assessed using a patient, intervention, comparison, and outcome (PICO) strategy. The best existing evidence is evaluated for relevance and involvement in CAT to propose a management plan for nintedanib-induced diarrhea. The selected studies underwent a risk of bias assessment.
Results: Of the 347 reviewed articles, nine relevant studies emerged. Among these, one systematic review and one randomized controlled trial (RCT) were identified, with the remaining studies being non-comparative cohort studies or case studies. These studies included a broad spectrum of pharmacological, non-pharmacological, and traditional (complementary) medical interventions. Most of these interventions have been investigated only once. Some studies had some risk of bias, but the majority had low risks.
Conclusion: The existing evidence is too weak to form a treatment guideline for nintedanib-induced diarrhea. Further investigation to the pathophysiological mechanisms underlying nintedanib-induced diarrhea and research in the form of randomized controlled trials (RCTs) are necessary for the development of treatment guidelines for diarrhea caused by nintedanib.



Patients with drug-induced diarrhea
Interventions (pharmacological and non-pharmacological)
NRS score
Primary outcome: reduced diarrhea Secondary outcome: side-effects

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