Therapy Management in Patients Treated With Anakinra Due to Recurrent Pericarditis

Azienda Ospedaliero, Universitaria Ospedali Riuniti

Status: Enrolling

Conditions: Recurrent Pericarditis

Treatments: Drug: Anakinra

Study type: Interventional

Funder types: Other

Identifiers

NCT06071156

CCPC- 003/18

Details and patient eligibility

About

To determine the utility of serial cardiac magnetic resonance (CMR) imaging for guidance of therapy management in patients treated with anakinra due to recurrent pericarditis (RP), compared with c-reactive protein (CRP) assay alone.

Full description

Recurrent pericarditis (RP) is a specific pathology of the pericardium included within the pericardial syndromes by the guidelines of the European Society of Cardiology (ESC). The latter defines RP as pericarditis occurring after a symptom-free interval of 4-6 weeks from a documented first episode of acute pericarditis; the recurrences rate may range from 15 to 30%, with a significant increment of 50% in patients treated with corticosteroids or not treated with colchicine. The diagnosis of recurrences follows the same criteria utilized for acute pericarditis, and a viral etiology can often be demonstrated.

The pathogenesis of RP is still debated, but they are self-sustained by an autoinflammatory/ autoimmune amplified response following an exogenous or endogenous trigger. In this context, the cytokine interleukin 1 (IL-1) has been implicated as a key mediator of RP. Anakinra, an IL-1 antagonist, is of particular interest because it limits the self-sustained pathway of RP and may reduce the recurrences. The current 2015 ESC guidelines for the diagnosis and management of pericardial diseases recommend anakinra in cases of proven infection-negative, corticosteroid-dependent RP not responsive to colchicine, but it remains debated the duration of the therapy and when to start its tapering. In this context, cardiac magnetic resonance (CMR) imaging has recently emerged as an interesting imaging biomarker capable of detecting pericardial inflammation, proving pericardial edema and late gadolinium enhancement (LGE), and distinguishing three defined pericardial inflammation phases: acute (edema and LGE), subacute (only LGE) and burned-out (no edema nor LGE).

To overcome the 2015 ESC guidelines limitations, the investigators sought to determine the utility of serial CMR imaging for guidance of therapy management in patients treated with anakinra due to RP, compared with the c-reactive protein (CRP) assay alone, as currently recommended.

Enrollment: 20 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients treated with anakinra 100 mg/die if ≥ 18 years old, and
• Pediatric patients treated with anakinra 2 mg/kg/die if < 18 years old
• Pediatric and adult patients treated with anakinra due to corticosteroid-dependent or not responsive to colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) recurrent pericarditis

Exclusion criteria

• Ongoing infection (proved within serology)
• Refuse to participate in the trial

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

CMR-guided therapy management,

Active Comparator group

Description:

The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Cardiac magnetic resonance \[no pericardial edema and/or late gadolinium enchantment (LGE)\] guided each anakinra dose reduction. If the tests were positive for ongoing pericardial inflammation \[pericardial edema present or LGE present\], the reduction was postponed, and one more month of therapy was administered before the reduction.

Treatment:

Drug: Anakinra

CRP-guided therapy management,

Active Comparator group

Description:

The scheme of Anakinra treatment was three months at full dosage, the next three months of therapy at full dosage every other day, and the last three months at halved dosage every other day until the end of treatment. Laboratory tests \[C-reactive protein (CRP) \<0.6 mg/dL\] guided each anakinra dose reduction. If the tests were positive for ongoing systemic inflammation (CRP \> 0.6 mg/dL), the reduction was postponed, and one more month of therapy was administered before the reduction.

Treatment:

Drug: Anakinra