Anakinra for RA and Refractory Idiopathic Recurrent Pericarditis

Anakinra (Kineret, Swedish Orphan Biovitrum), an interleukin-1 (IL-1) receptor antagonist, is indicated to reduce signs and symptoms of, and to slow progression of structural damage in, moderately to severely active rheumatoid arthritis (RA) in patients 18 years of age or older who have failed one or more DMARDs.¹

The IL-1 pathway may also play an important role in the pathogenesis of refractory idiopathic recurrent pericarditis (IRP), and IL-1 antagonists such as anakinra may be potential treatment options. Defined as recurrence of pericarditis of unknown origin after a first episode of acute pericarditis and a symptom-free interval of 4 to 6 weeks or longer, IRP may result in decreased quality of life and corticosteroid dependence.² Patients who do not respond to initial therapy with aspirin or NSAIDs plus colchicine may have an autoimmune mechanism of pericarditis.^2,3

The efficacy of anakinra in the treatment of IRP was first demonstrated in the pediatric population. Its use in adults has been primarily limited to case reports and retrospective analysis. Recently, Brucato and coworkers³ assessed its efficacy in patients with refractory IRP who were corticosteroid dependent and colchicine resistant. The randomized, double-blind, placebo-controlled study included 21 adult and pediatric patients with IRP (3 or more previous recurrences). Anakinra was administered at 2 mg/kg per day, up to 100 mg, for 2 months. Patients who responded with resolution of pericarditis were randomized to continue anakinra (n=11) or to switch to placebo (n=10) for 6 months or until a pericarditis recurrence. The primary outcomes were recurrent pericarditis and time to recurrence after randomization.

Recurrent pericarditis occurred in 9 of 10 patients (90%) in the placebo group, and 2 of 11 patients (18.2%) receiving anakinra. Median flare-free survival was 72 days after randomization in the placebo group, and was not reached in the anakinra group (P<0.001). The most common adverse event in the anakinra-treated patients was transient local skin reactions at the injection site (20/21 patients; 95.2%). Other study-related side effects included herpes zoster (4.8%), transaminase elevation (14.3%), and ischemic optic neuropathy (4.8%). No patient permanently discontinued the active drug. 

In clinical trials in RA, an increased incidence of serious infections, including bacterial pneumonia and cellulitis, was seen in anakinra-treated patients. Treatment with anakinra should not be initiated in patients with active infections, and live vaccines should not be administered concurrently.

Drugs that affect the immune system by blocking tumor necrosis factor (TNF) have been associated with an increased risk of reactivation of latent tuberculosis. Therefore, it is possible that medications such as anakinra that block IL-1 may increase risk of TB. Health-care providers should follow current CDC guidelines both to evaluate for and to treat possible latent TB infections before initiating anakinra therapy.⁴ Because patients receiving anakinra may experience neutropenia, neutrophil count monitoring is recommended before initiating therapy, then monthly for 3 months, and quarterly for up to 1 year thereafter. Anakinra is primarily excreted by the kidney; therefore, dosage adjustment is recommended in patients with severe renal insufficiency or end-stage renal disease (ie, creatinine clearance <30 mL/min). 

References:

1. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) Eur Heart J. 2015;36:2921–2964.

2. Schwier NC, Hale GM, Davies ML. Treatment of adults with idiopathic recurrent pericarditis: novel use of immunotherapy. Pharmacotherapy. 2017;37:305-318.

3. Brucato A, Imazio M, Gattorno M, et al. Effect of anakirna on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence: the AIRTRIP randomized clinical trial. JAMA. 2016;316:1906-1912.

4. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recomm Rep. 2000;49(RR-6):1-51.