PBC-Related Fatigue: Which Therapies are Effective?
In a recent systematic review, researchers with Beth Israel Deaconess Medical Center found few interventions under investigation for the treatment of primary biliary cholangitis-related fatigue improved patients’ symptoms.1
Fatigue is a common symptom among patients with primary biliary cholangitis (PBC). Despite this, treatments options for PBC-related fatigue are limited.
“Fatigue is one of the most common complaints in patients with PBC,” said corresponding author Alan Bonder, MD, in an interview with Consultant360. “For treating fatigue, we really do not have a good armamentarium of medications available to help patients.”
He and his colleagues searched the literature and identified 16 studies, which examined the efficacy of ursodeoxycholic acid (UDCA), liver transplantation, serotonin reuptake inhibitors, colchicine, methotrexate, cyclosporine, modafinil, and obeticholic acid for PBC-related fatigue. The proportion of patients with fatigue or reduction in the degree of fatigue was assessed as the primary outcome, along with adverse events.
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Overall, their analysis showed that treatment with UDCA was not associated with a reduction in the risk of fatigue (relative risk [RR] 0.86). The degree of fatigue was reduced among patients treated with liver transplantation, however, it did not return to baseline. According to Bonder et al, this indicated that the underlying cause of fatigue might not have been addressed.
“While there is some improvement in fatigue with liver transplantation, there is a lack of high-quality evidence supporting the efficacy of any other intervention in the treatment of PBC-related fatigue,” Bonder and his colleagues concluded. “Further research into the underlying pathophysiology may help guide future trials.”
Dr Bonder recommends specialists who treat patients with PBC to evaluate them for other chronic conditions related to fatigue and to determine if there are other reasons why a patient with PBC might be experiencing fatigue.
“PBC can be a comorbid condition with other autoimmune diseases, which need to be ruled out,” said Dr Bonder.
If autoimmune or other comorbid conditions are not present in the patient, he suggests clinicians work with the patient and try a few of the options he and his colleagues recommend in their paper to determine if the patient would benefit from different medical therapies.
“Although we have made a lot of advances and improved these patients’ quality of life, at the end of the day, most of our patients will still complain of fatigue,” said Dr Bonder. “And, patient lack therapies for this besides a liver transplant, which is the only intervention that showed improvements in quality of life. However, most patients would like other therapeutic options before undergoing this intervention.”
“In the future, I hope we can run a clinical trial with fatigue as an endpoint, which is not a very quantifiable and objective measurement,” Dr Bonder added.
Beth Israel runs the Autoimmune and Cholestatic Liver Disease Program, which provides care for patients with autoimmune-related liver complications such as autoimmune hepatitis, PBC, primary sclerosing cholangitis, IB-related liver disease, and more. The program offers multidisciplinary care to patients and operates several clinical trials to better understand these autoimmune diseases and explore new treatment options. For information about the clinic and clinical trials, please visit https://www.bidmc.org/centers-and-departments/digestive-disease-center/services-and-programs/liver-center/programs-and-services/autoimmune-and-cholestatic-liver-disease.
Reference
1. Lee JY, Danford CJ, Trivedi HD, Tapper EB, Patwardhan VR, Bonder A. Treatment of Fatigue in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis [published January 10, 2019]. Dig Dis Sci. doi:10.1007/s10620-019-5457-5