Background/Purpose: Deficiency of interleukin-1 receptor antagonist (DIRA) is a neonatal-onset autoinflammatory syndrome caused by recessive mutations in IL1RN gene, the gene encoding the interleukin-1-receptor antagonist. It is clinically characterized by a perinatal-onset of pustular dermatosis, aseptic multifocal osteomyelitis, and marked elevation of acute phase reactants. In our treated patients, IL-1 blockade with daily anakinra leads to rapid and complete resolution of symptoms and normalization of the acute phase reactants. There is a need, however, for longer acting IL-1 blocking agents that are more convenient to administer and are less likely to cause injection site reactions.  

Objectives: The primary objective of this study is to assess the ability of rilonacept to achieve/maintain remission in patients with DIRA who have shown response to anakinra. The secondary objective is to assess the safety of rilonacept in DIRA patients, and to assess its ability to prevent new organ damage. 

Methods: Patients with a genetically confirmed diagnosis of DIRA and an adequate response to anakinra are eligible for the study. Per protocol, anakinra was discontinued 24 hours prior to first dose of study medication.  A loading dose of rilonacept of 4.4 mg/kg/ week was given and then decreased to a maintenance dose of 2.2 mg/kg/week. Patients who met flare criteria were subsequently escalated to 4.4 mg/kg/week with the option to increase to 6.6 mg/kg/week if needed. Diary and Dermatology scores in addition to ESR and CRP were collected at each visit.  Paired t-test analyses were used to compare baseline and the most recent clinic visit data.

Results: Six Caucasian patients have been enrolled, 50% male, with a mean age of 4.8 years SD (±1.3). All patients were in remission on anakinra (diary score 0) with a mean dosage of 3.21 mg/kg/day SD (±0.48). The mean follow-up time has been 4.5 months. The diary scores have increased to 0.09 at the last visit, reflecting the onset of nail changes in one patient.  All patients (except one) required an escalation in dosage from 2.2 mg/kg/week to 4.4 mg/kg/week due to a transient increase in micropustular lesions mostly in hyperkeratotic areas of the skin (elbow and knee). The micropustular lesions lead to the increase in dermatology scores from 1.3 to 3.2. Despite the mild skin lesions, no new bone lesions were detected and the acute phase reactants have decreased from baseline. No SAE’s have occurred and four adverse events have been reported.

Conclusion: Preliminary data in six DIRA patients suggest that doses of rilonacept at 4.4 mg/kg/week are required to achieve remission. Rilonacept treatment provides increased quality of life due to weekly injections. Long acting IL-1 inhibition with rilonacept seems to be a viable option in the treatment of DIRA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-and-efficacy-of-rilonacept-in-patients-with-deficiency-of-interleukin-1-receptor-antagonist-dira/