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

CAT | 2023
Samenvatting

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.

Specialisme
Longgeneeskunde
Opleiding
Master

PICO

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

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