Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review

Abstract

Background: Interleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified.

Objective: Identify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review.

Patients and methods: Data were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases.

Results: Complete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients' quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature.

Conclusion: In the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.

Keywords: anakinra; autoinflammatory diseases; canakinumab; hereditary recurrent fevers; indications; interleukin-1 blockers; treatment.

Figure 1

(A) FMF–Definition of colchicine resistance and literature review. (B) Previous treatments to IL-1 inhibitors. (C) Reasons for discontinuing steroids–Literature review. (D) Reasons for discontinuing anakinra. IL, interleukin; FMF, familial Mediterranean fever; MKD, mevalonate kinase deficiency; TRAPS, tumor necrosis factor receptor-associated periodic syndrome; LR, literature review.

Figure 2

(A) Severe clinical complications. (B) Attacks’ characteristics–literature review. (C) Decreased quality of life. FMF, familial Mediterranean fever; MKD, mevalonate kinase deficiency; TRAPS, tumor necrosis factor receptor-associated periodic syndrome; LR, literature review; GNMP, membrano-proliferative glomerulonephritis; MAS, macrophage activation syndrome; AIMD, auto-immune disease.

Figure 3

(A) Biological activity at IL-1 inhibitors’ start. (B) HRF activity at IL-1 inhibitors’ start. IL, interleukin; HRF, hereditary recurrent fever; FMF, familial Mediterranean fever; MKD, mevalonate kinase deficiency; TRAPS, tumor necrosis factor receptor-associated periodic syndrome; LR, literature review; CRP, C-reactive protein; SAA, serum amyloid A protein.