Azathioprine as a Steroid-Sparing Agent for Idiopathic Recurrent Pericarditis

By Adam Brown, MD, and Soumya Chatterjee, MD, MS, FRCP

Patients with idiopathic recurrent pericarditis (IRP) require prolonged courses of glucocorticoids (GC) to prevent and treat flares. GC use contributes to the high morbidity of this disease; in a search for ways to reduce that morbidity, we conducted a retrospective study to evaluate the use of azathioprine (AZA) as a steroid-sparing agent for patients with IRP.

Our findings, presented at the 2015 annual meeting of the American College of Rheumatology, suggest that AZA may in fact provide value for some patients.

Years of glucocorticoids for IRP patients

IRP refers to pericarditis not associated with an underlying autoimmune rheumatic condition. The etiology of IRP is unproven, but substantial evidence supports autoimmune or autoinflammatory involvement.

Considering IRP’s suspected autoimmune etiology, the Department of Rheumatic and Immunologic Diseases collaborates with The Sydell and Arnold Miller Family Heart and Vascular Institute to evaluate and co-manage many patients with IRP. About five percent of IRP cases will not respond adequately to triple therapy; the mean duration of symptoms in these cases is 5.4 years. Complications of recurrences, evaluated in multiple case studies, show a 3.2 percent risk of cardiac tamponade and a 0.6 percent risk of pericardial constriction.

Many patients with IRP take GCs for months to years, leading to a variety of side effects including weight gain, diabetes, osteoporosis and hypertension. In published case reports and case series, AZA has often been used as a steroid-sparing agent when patients with IRP show evidence of chronicity and fail conventional triple therapy for several months.

A retrospective look at azathioprine use in IRP

In our retrospective study of a cohort of patients with IRP, we compared the average and cumulative GC dose requirement over a six-month period before and after initiation of AZA. We evaluated all Cleveland Clinic patients with IRP seen between January 2003 and December 2015 who were started on AZA. Of these patients, 13 were selected who had adequate GC data before and after initiation of AZA. We determined the amount of GC required in two-week intervals over the course of six months and documented each pericarditis flare. Since the onset of action of AZA is thought to be about two to three months, we documented the number of flares between months three and six.

The majority of IRP cases were considered idiopathic or post-viral, and a few had history of myopericardial injury. Patients had an average disease duration of more than eighteen months prior to the initiation of AZA, and all but one had at least six months of prior, continuous prednisone use.

AZA shows value as adjunct in IRP

We found that the addition of AZA did allow for a statistically significant overall decrease in the amount of GCs required to control disease activity and prevent flares of IRP in the subsequent six months. Moreover, the mean daily GC dose requirement was reduced, and the overall number of flares of IRP decreased significantly. Our results show that AZA may be a viable, inexpensive option as a steroid-sparing agent in patients with IRP who fail triple therapy. We continue to gather data on more patients and for longer periods of time to better evaluate the efficacy of various immunosuppressive medications as steroid-sparing agents in IRP.

Dr. Brown is a fellow in the Department of Rheumatic and Immunologic Diseases. Dr. Chatterjee directs the Scleroderma Program in the Department of Rheumatic and Immunologic Diseases.