Background/Purpose

Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disorder characterized by recurrent episodes of fever accompanied by sterile peritonitis. The most devastating complication of FMF is  the development of secondary amyloidosis which has a potential risk for developing end stage renal disease. However cholchicine is the most effective treatment regimen in FMF patients, 5-10% of patients are refractory. However, there are several drugs being tested in this group of patients. The most promising group of drugs appears to be the anti-IL-1 therapies. The objective of this study is to demonstrate the efficacy of anakinra and canakinumab in FMF patients who followed up in our outpatient clinics.

Methods

In this study we included 20 cholchicine resistant FMF patients (16 adults and  4 children) diagnosed according to the Tel–Hashomer or Sheba Medical Center criteria, who are receiving anti-IL-1 treatments (anakinra n= 12 or canakinumab n= 8). A retrospective review of medical records of anti-IL-1 recipients was performed. The main clinical characteristics of these patients and their genotypes for MEFV gene and the evolution after anti-IL-1 were recorded laboratory response was evaluated with erythrocyte sedimentaion rate(ESR) and C-reactive protein (CRP ).

Results

The median age of patients was 23 (14-50) , the median disease duration was 16 years (4-46) and the median follow up time in clinic was 12 years (1-26). 16 were homozygous for the M694V mutation.  Attacks per month and year were significantly  decreased after anti IL-1 theraphy p < 0.05 (Table 1). The median follow-up of the anakinra and canakinumab patients were 14 (4-36) and 18 (4-25) months respectively (p = 0.51). All patients were also receiving background colchicine with a median dose of 1.5 mg. there is a trend towers a decreasing dose of colchicine after anti-IL-1. Acute phase responses were aslo significantly decreased after IL-1 treatments (p < 0.05, Table 1). Besides the effectiveness on acute attacks we also noted significant decreases in proteinuria in patients with amyloidosis (9 gr to 3.7 gr/day in the adult and 25.6 mg/m²/hour to 12 mg/m²/hour in the pediatric patient). In a median 16 months of follow-up there were only one serious adverse event (pneumonia) in a patient receiving anakinra therapy However, after antibiotic treatment we resumed treatment in this patient.

Conclusion

In this study we revealed that 95% of our colchicine-resistant patients responded to the anti-IL-1 targeting agents. These drugs tolerated well and only one patient had serious adverse events during the 16 months of follow-up. We also noted significant ameloration of proteinuria in amyloidosis patients. IL-1 receptor antagonists anakinra and canakunimab seem to be  safe and effective treatment options in colchicine-refractory FMF patients.

	Attacks/mo (Before treatment)	Attacks/mo (After treatment)	p	Attacks/year (Before treatment)	Attacks/year (After treatment)	p
Anti-IL-1 (n:20)	1.5 (1-4)	0 (0-3)	<0.0001	15 (5-50)	0.5 (0-24)	0.001
Anakinra (n:12)	2.5 (1-4)	0 (0-3)	0.003	30 (12-50)	2 (0-24)	0.018
Canakunimab (n:8)	1 (1-2)	0	0.007	10 (2-20)	1 (0-2)	0.018
	CRP mg/l (Before treatment)	CRP mg/l (After treatment)	p	ESR mm/h (Before treatment)	ESR mm/h (After treatment)	p
Anti-IL-1 (n:20)	52.5 (5-195)	4.5 (0.6-53)	<0.0001	41 (8-110)	12 (5-100)	<0.0001
Anakinra (n:12)	43.3 (5-195)	5 (0.7-53)	0.003	42 (8-110)	14 (5-100)	0.004
Canakunimab (n:8)	52.5 (5.4-140)	3.7 (0.6-7)	0.001	37 (14-57)	11 (6-55)	0.001

Table 3: Number of attacks and acute phase protein levels before and after anti-IL-1 treatment

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-interleukin-1-targeting-drugs-in-familial-mediterranean-fever-patients/