Background/Purpose: Systemic Autoinflammatory Diseases (SAIDs) are a group of rare disorders caused by dysregulation of the innate immune system. Over 50 genes have been identified as causative for SAIDs. However, 40-60% of patients presenting with features consistent with SAIDs remain without a definitive diagnosis and are often categorized as undifferentiated SAIDs (uSAIDs). Treatment can be challenging due to heterogeneous presentations and uncertain disease mechanisms. This study aimed to evaluate the clinical and laboratory response to IL-1 blockade in pediatric patients with uSAIDs.

Methods: We conducted a retrospective chart review of patients diagnosed with uSAIDs and treated with IL-1 inhibitors (anakinra, canakinumab, or rilonacept) at a single tertiary pediatric center between January 2010 and December 2023. Inclusion required a clinical diagnosis of uSAID, treatment with IL-1 blockade, and documented follow-up within one year of initiation of treatment. Data collected included demographics, clinical phenotype, flare frequency and severity, laboratory markers (CRP, CBC), treatment characteristics, and adverse events. Response to treatment was assessed through laboratory values, clinical presentation, the need for rescue medications, and the overall physician assessment of improvement.

Results: Thirty-three patients (51.5% female) with uSIADs who contributed to fifty-five IL-1 blockade treatment instances were identified. The mean age at symptom onset was 4.3 years (range 0–20), and the mean age at diagnosis was 7.8 years (range 0.6–21). All patients underwent genetic testing not revealing a known monogenic systemic autoinflammatory disease. Common clinical features included recurrent fevers (87.9%), arthralgia (57.6%), abdominal pain (51.5%), and urticarial rash (42.4%). Most patients (75.8%) had trialed colchicine before starting IL-1 blockade. Treatments included Anakinra (49%), canakinumab (45.5%), or Rilonacept (5.5%). Rescue medications were used in 49.1% of instances with corticosteroids being the most common in 55.6%, NSAIDs in 37.0% and Anakinra in 7.4%. Flares occurred a mean of 4.11 per month (range 0.5–30) at baseline which reduced to a mean of 0.8 (range 0-3) per month on first follow up after initiating treatment. Physician-assessed clinical improvement was noted in 92.7% of treatment instances. CRP levels decreased from a mean of 3.38 ± 7.06 mg/dL pre-treatment to 0.45 ± 1.49 mg/dL post-treatment (normal < 0.5 mg/dL). Treatment was generally well-tolerated; adverse events occurred in 11% of instances, most commonly injection site reactions and elevated liver enzymes. At last follow-up, 97% remained on IL-1 therapy, most commonly canakinumab.

Conclusion: Our study demonstrates that IL-1 blockade therapy can yield favorable outcomes in patients with uSAIDs, as reflected by improvements in flare frequency and decreased reliance on rescue medications clinically and improved inflammatory markers. These findings underscore the potential of IL-1 blockade as an effective therapeutic strategy for this challenging patient population. Nevertheless, additional research is essential to validate these results and establish standardized treatment protocols for uSAIDs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/real-world-experience-with-il-1-blockade-in-children-with-undifferentiated-systemic-autoinflammatory-diseases-usaids/