This is Familial
Mediterranean Fever
(FMF)

FMF is an autoinflammatory disorder associated with mutations in the MEVF gene leading to overproduction of interleukin-1β (IL-1β)¹

FMF is the most common inherited monogenic autoinflammatory disease and affects mainly ethnic groups from the eastern Mediterranean area. However, due to worldwide migration, FMF is also found beyond mediterranean countries and even in populations with no recent ancestry to mediterranean countries. FMF is one of the periodic fever syndromes.^2-5

for illustrative purposes only - region around the mediterranean sea

FMF is almost always restricted to Turks, Armenians, Arabs, and non-Ashkenazi Jews^4,6

• Turkey - Probably the country with the highest prevalence, Estimated prevalence: 1:400 to 1:1,000 (highest in the areas of Anatolia). >100,000 FMF patients in total⁴
• Armenia - Prevalence estimated to 1:500, 6,000 in total⁴
• Germany - Most FMF patients are from Turkish origin⁴
• France - Prevalence 1:5,000, Total: 5-10,000 patients, Most FMF patients from North African origin^4,7
• Greece, Cyprus - 1:25 Greek-Cypriots is a carrier of one of the three most common mutations in MEFV⁸
• Japan - ~100 patients⁴
• Jordan, Syria, and Lebanon- many FMF patients but exact number not known⁴
• Israel - Prevalence 1:1,000 (depending on ethnic group)⁴
• Italy - No longer a rare disease. More patients in central and southern parts^4,9

In patients with FMF, mutations in the MEFV gene encoding for pyrin leads to malfunctioning of the pyrin inflammasome and overproduction of interleukin-1 (IL-1β).¹⁰ FMF is characterised by recurrent, self-limited episodes of fever accompanied by inflammation and serositis. Abdominal pain is a common feature during febrile attacks, and chest pain, myalgia and rash can also be present. FMF often begins in childhood or adolescence, and the frequency and severity of attacks can vary widely between individuals.^4,5,11 FMF is diagnosed clinically but can be supported but not excluded by genetic testing.⁴

A severe complication of FMF is the development of secondary amyloidosis (AA amyloidosis*), which is the result of prolonged and uncontrolled inflammation and can ultimately lead to renal failure.¹²

Common signs and symptoms associated with FMF^4,13,14

A valuable asset for the treatment of FMF

The goals of treatment in FMF are to prevent acute attacks, minimise subclinical inflammation in between attacks, and prevent the development and progression of amyloidosis.¹²

Adding an IL-1 inhibitor like Kineret may be an alternative for patients who do not respond to or cannot tolerate colchicine. In a systemic literature review, complete response to therapy without a single attack during treatment was reported in 76.5% of patients on anakinra treatment.¹⁵ Patients also experienced a decrease of proteinuria after initiating Kineret.¹⁵

In the randomised controlled trial “Anakinra for Colchicine-Resistant Familial Mediterranean Fever”, Kineret had a favorable efficacy and safety profile in patients who failed to reach their treatment goals with colchicine.

Adding Kineret reduced the number of attacks per month and significantly improved patients' QoL scores^1,16

Adapted from: Table 2, Ben-Zvi et al. 2017. Anakinra for Colchicine-Resistant Familial Mediterranean Fever.

Patients who achieved improvement with Kineret¹⁶

Adapted from: Figure 3, Ben-Zvi et al. 2017. Anakinra for Colchicine-Resistant Familial Mediterranean Fever

The proportion of patients who experienced improvement with either Kineret or placebo treatment was assessed using the modified familial Mediterranean fever 50% improvement (FMF50) score. Improvement percentages in each group were determined based on meeting at least three out of four criteria: a reduction of at least 50% in the total number of attacks, the number of joint attacks, C-reactive protein (CRP) and serum amyloid A (SAA) levels (or reaching normal values, defined as ≤5 mg/liter for CRP and ≤10 mg/liter for SAA), and quality of life rating.¹⁶

* AA Amyloidosis can occur as a response to a chronic inflammatory disease or infection. These conditions cause the liver to produce high levels of a protein called serum amyloid A (SAA), which may form abnormal fibril protein aggregates in tissues and organs, leading to AA amyloidosis.

Abbreviations

MEFV, Mediterranean Fever (MEditteranean FeVer gene); FMF50 score required improvement by ≥50% in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attackswitharthritis,andlevelsofacute-phasereactants)withoutworseningofthesixthcriterion; CRP,C-reactive protein; SAA, serum amyloid A; QoL, Quality of life; IL-1, Interleukin-1; IL-1β, Interleukin-1 beta