Treatment of Adults with Idiopathic Recurrent Pericarditis: Novel Use of Immunotherapy

Abstract

Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Because it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged. In this review, we describe the literature associated with immunotherapy used to treat IRP in an adult population as well as provide an overview of the safety and monitoring parameters for each agent. The most common immunotherapies used after patients have had multiple recurrences of IRP are anakinra, intravenous immunoglobulin (IVIG), and azathioprine. In most cases, these immunotherapies are adjunctive therapy, with the goal of tapering and discontinuing immunosuppressive corticosteroids. After reviewing the data, anakinra resulted in more patients discontinuing corticosteroids and prevented further recurrences of pericarditis. IVIG resulted in symptom resolution and no further recurrences in most of the patients. Azathioprine was associated with more than half of patients becoming recurrence free; however, many patients required a restart of corticosteroids due to recurrence. Clinicians should be aware of the adverse effects of immunotherapy, ranging from mild gastrointestinal events to risk of infection and serious blood dyscrasias that may require diligent monitoring. The use of immunotherapy for the treatment of adults with IRP should be restricted to patients who have multiple recurrences. Ideally, immunotherapy would be adjunctive to first-line combination therapy with ASA/NSAID plus colchicine, with the goal of tapering and discontinuing immunosuppressive corticosteroids. Furthermore, clinicians should consider cost, drug-drug and drug-disease interactions, and safety, as well as the quality of the retrospective evidence before considering any immunotherapy.

Pharmacotherapeutic Management Strategies for Thyroid Disease–Induced Pericarditis

“…Immunotherapy for the management of pericarditis is an evolving field and is usually reserved for patients who have recurrent pericarditis that is refractory to combination therapy with ASA/NSAIDs plus colchicine as well as corticosteroid therapy. 51 To date, there has been no documented report of recurrent pericarditis secondary to thyroid disease, making it difficult to ascertain the safety and efficacy of immunotherapies in the treatment of TDIP. Clinicians should also consider the impact of the adverse comorbidities that result from thyroid disease, such HTN, HF, CAD, and supraventricular tachycardias because there could be drug-disease and/or drug-drug interactions associated with treatment of adverse comorbidities, thyroid disease, and pericarditis.…”

Pharmacists’ Role in the Management of Acute and Recurrent Pericarditis: Inpatient and Outpatient Perspectives

“…10 Since the pharmacotherapies used to treat idiopathic pericarditis, such as high-dose ASA or NSAIDs and colchicine can be associated with drug–drug interactions, drug–disease interactions, and adverse effects (some of which can be potentially life-threatening), pharmacists can be utilized in various health-care settings in helping to treat patients with pericarditis. 12 -15 Aside from the previously described medication safety considerations, the 2015 ESC guidelines’ recommendation for colchicine is based on the European dosage form of colchicine—the 0.5 mg tablet. 1,7 -11 In the U.S., however, a 0.6 mg tablet and capsule formulation are currently available, making it challenging to extrapolate 2015 ESC guidelines’ recommendations to US patients.…”

“…15 Subsequently, there has been an upwelling of data regarding the use of immunotherapies for the treatment of recurrent pericarditis. 12 Currently, the 2015 ESC guidelines recommend the use of immunotherapies as third- line in patients who have recurrence, despite using ASA/NSAID and colchicine, which occurs while attempting to wean patients from corticosteroids. 1 Immunotherapies such as anakinra and intravenous immunoglobulin must be initiated in the hospital due to weighing the risk of preventing recurrences against exacerbating some of their potentially serious adverse effects.…”

“…1 Immunotherapies such as anakinra and intravenous immunoglobulin must be initiated in the hospital due to weighing the risk of preventing recurrences against exacerbating some of their potentially serious adverse effects. 12 Such medications have been previously reviewed, but the inpatient clinical pharmacists should especially consider drug–disease interactions, adverse effects, encouraging the medical team to consult with rheumatology, and cost of such agents, prior to recommending initiation of immunotherapies for the treatment of recurrent idiopathic pericarditis that occurs during corticosteroid tapering. 1,12…”

“…27 Immunoglobulin is typically dosed 400 mg/kg/d for 5 days for flares of recurrent pericarditis, then monthly. 12 Pricing for immunoglobulin ranges from $15.00 to over $1,000.00 per 5 g. 28 Consequently, cost is an important consideration in patients using immunotherapy to treat recurrent pericarditis, as patient affordability concerns may delay treatment, potentially leading to future recurrences of pericarditis, and similar to colchicine, immunotherapies can be expensive, since they often require patients to use them for months to years. 10 Being a part of a multidisciplinary pharmacy and therapeutics (P&T) committee, managed care pharmacists can be involved in the creation, management, and/or updating process of third-party payer organization formularies.…”