Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis

Recurrent pericarditis is a debilitating condition that can be recalcitrant to conventional therapy with nonsteroidal anti-inflammatory agents, colchicine, and glucocorticoids. The aim of this study was to evaluate the therapeutic role of the recombinant interleukin-1 receptor antagonist anakinra in a series of adult patients with recurrent pericarditis refractory to conventional therapy. We retrospectively reviewed the medical records of 13 consecutive patients with treatment-refractory recurrent pericarditis who received anakinra for management of their disease. None of the patients had an identified systemic inflammatory rheumatic disease. The primary end points were symptom resolution and glucocorticoid discontinuation. Thirteen patients (10 women) treated with anakinra were followed for a median (range) of 16.8 months (1.3 to 24). All patients had chest pain. Total duration of symptoms before initiation of anakinra was 3 years (1.1 to 6.0). Pericardial thickening was detected by echocardiography in 9 patients (69%). All 13 patients (100%) experienced at least a partial and, most, a complete resolution of symptoms. Response to therapy was rapid, within 2 to 5 days. At last follow-up, 11 patients (84%) had successfully discontinued concomitant nonsteroidal anti-inflammatory agent, colchicine, and glucocorticoid therapy; 11 patients remained on anakinra at the end of the follow-up period. The only side effect was transient injection site reaction in 4 patients (31%). In conclusion, anakinra may be an effective alternative agent for the management of glucocorticoid-dependent recurrent pericarditis. Side effects were minor. A formal clinical trial to evaluate the usefulness of this agent should be considered.

Anakinra is a recombinant human interleukin-1 competitive receptor antagonist that blocks the biologic effects of interleukin-1, an endogenous cytokine, thereby reducing systemic inflammatory responses. It is classified as a biologic agent that has been successfully studied in randomized trials as an effective treatment option for rheumatoid arthritis and other systemic autoimmune and autoinflammatory diseases. Case reports describing successful treatment of refractory pericarditis in adults and children have been encouraging. We report our experience with this agent in series of adult patients with recurrent pericarditis refractory to conventional therapy.


The medical records of 13 patients with recurrent pericarditis, refractory to conventional therapy, who received anakinra for management of this disease, were retrospectively evaluated. All patients had been referred to the Pericardial Diseases Clinic at the Mayo Clinic. Recurrent pericarditis was defined as recurrent or persistent symptoms of pericarditis despite appropriate medical therapy, with a documented history of first attack of acute pericarditis according to the currently accepted diagnostic criteria. Patients were deemed eligible for anakinra therapy at the discretion of 2 clinicians (at least 1 each from cardiology and rheumatology) experienced in the management of complex pericardial diseases. Patients with active infection and those with postsurgical, radiation-induced, autoimmune disease–related, tuberculous, or purulent pericarditis were excluded.

At the time anakinra was prescribed, all patients had failed maximally tolerated doses of nonsteroidal anti-inflammatory agents (NSAIDs), colchicine and prednisone, administered for at least 6 months. Standard baseline testing before anakinra initiation was obtained in all patients and consisted of TB Mantoux test or serum quantiFERON, Westergren erythrocyte sedimentation rate (ESR), C-reactive protein (C-RP), antinuclear antibody, rheumatoid factor, serum protein electrophoresis, hepatitis B and C screening, and fungal antibody survey. All 13 patients underwent echocardiography (echo) and 8 patients also underwent cardiac magnetic resonance imaging (cMRI) before initiation of anakinra. Troponin T was undetectable in the 2 patients in whom it was tested. Anakinra was initiated at a standard dose of 100 mg once daily by self-administered subcutaneous injection. The initial treatment was 6 months. In addition to medical record review, late follow-up of symptoms and quality of life for all patients was determined through telephone interview by a single cardiologist (SJ). The Mayo Clinic Institutional Review Board approved the study.


Thirteen patients with refractory pericarditis (12 idiopathic and 1 postinfarction) were followed for a median (range) of 23.6 months (15.1 to 42.9). Study subjects were predominantly women (77%). The median age on commencement of anakinra was 49 (interquartile range [IQR] 41 to 58) years. The median age at initial episode of pericarditis was 47 (IQR 39 to 54) years. The primary symptom was chest pain in all patients. Five patients (38%) also had concurrent dyspnea. Antinuclear antibody was positive in 2 patients, C-RP was moderately elevated in 4 patients, and ESR moderately elevated in 3, including 1 patient with elevated C-RP. Baseline ejection fraction was 62% (55% to 67%). All patients had abnormal imaging findings at the initiation of anakinra therapy. Pericardial thickening was seen in 9 patients (69%). Constrictive physiology was seen in 1 patient (7%) on echocardiogram and 4 patients (31%) on cMRI. Pericardial enhancement was seen in 4 (50%) of 8 patients who had cMRI.

Total duration of symptoms before initiation of anakinra was 3 years (IQR 1.1 to 6.0; Table 1 ). The indications for anakinra initiation were (1) persistent debilitating symptoms despite prednisone, with or without NSAID in 5 (38%) and (2) as a glucocorticoid-sparing agent in 8 patients (62%) whose disease was well controlled with that therapy, all of whom had glucocorticoid-related side effects ranging from weight gain, hypertension, osteoporosis, and suicidal ideation.

Table 1

Anakinra treatment in 13 patients with refractory pericarditis. Prednisone dose is dose at initiation of anakinra

Patient Age (Years), Sex Pericarditis Duration (Years) Prior/current medication for pericarditis Response and duration of anakinra therapy at last follow-up
1 73 F 0.5 NSAID , Col , Pred (30 mg/d), MTX Asymptomatic; off Pred, NSAID, Col and MTX. On anakinra for 29.5 mos.
2 48 M 0.8 NSAID , Col , Pred (20 mg/d), MMF Excellent symptomatic improvement; off Pred and Col. Stopped anakinra after 13 months; flared; on anakinra 26 mos.
3 38 M 1 NSAID , Col , Pred (20 mg/d) Asymptomatic; off Pred, NSAID and Col. On anakinra 15 mos.
4 53 F 1 NSAID , Col , Pred (5 mg/d) Significant symptomatic improvement; off Pred, NSAID and Col. On anakinra 21 mos.
5 33 F 2 NSAID , Col , Pred (25 mg/d), HCQ, AZA Asymptomatic; off Pred, NSAID, Col and AZA. On anakinra 22.6 mos.
6 55 F 2 NSAID, Col, Pred (25mg/d), HCQ Significant pain control but not resolution. Pain recurred when missed anakinra for week. On anakinra 43 mos.
7 58 F 3 NSAID, Col , Pred (10 mg/d) Partial improvement in pain; Stopped anakinra after 2 mos; relapsed 4 months later. Improved on anakinra; 33 mos.
8 44 F 3 NSAID , Col Partial symptomatic improvement; off NSAID and Col. Experienced flare while on anakinra. On anakinra 33.5 mos.
9 58 F 5 NSAID , Col, Pred (20 mg/d), AZA Asymptomatic; Pred tapered to 1mg/d; stopped anakinra after 11 mos. No relapse for 6.5 mos.
10 46 M 6 NSAID, Col , Pred (5 mg/d), HCQ Asymptomatic; off Pred and Col; held anakinra for surgery. Anakinra re-initiated after relapse; on anakinra 20 mos.
11 49 F 6 NSAID, Col, Pred (10 mg/d) Excellent symptomatic improvement. Stopped anakinra after 2 years; flared; since on anakinra 17.5 mos.
12 38 F 12 NSAID , Col , Pred (20 mg/d) Asymptomatic; off Pred, NSAID and Col. Stopped anakinra after 8 mo. without relapse for 10 mos.
13 69 F 12 NSAID, Col Pred (20 mg/d) Excellent symptomatic improvement; Pain recurred when Pred <2mg/d and anakinra 50 mg/daily; on 100 mg daily for 26 mos.

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Nov 28, 2016 | Posted by in CARDIOLOGY | Comments Off on Effectiveness and Safety of Anakinra for Management of Refractory Pericarditis

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