The Use of Interleukine-1 Inhibitors in Familial Mediterranean Fever Patients: A Narrative Review

Abstract

Purpose: Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. It is associated with mutation in pyrin inflammasome leading to interleukin-1 (IL-1) over secretion. Although colchicine is the first line treatment in FMF, 5-10% of patients are reported in literature as non-responders. Colchicine is not always well-tolerated due either to its direct toxicity or to co-morbidities that preclude the administration of its proper dosage. For these patients an alternative or additional treatment to colchicine is necessary. This literature review reports the published data regarding the use of IL-1 inhibitors in Familial Mediterranean Fever. Results: There is no uniform definition of colchicine resistance, but the different studies of treatment with IL-1 inhibitors provide evidence of IL-1 pathogenic role in colchicine-resistant FMF. IL-1 inhibition is an efficacious option for controlling and preventing flares-at least at the short term-in FMF patients who are insufficiently controlled with colchicine alone. Although canakinumab is the only approved drug in Europe for colchicine resistant FMF treatment, experience with anakinra is also substantial. In the absence of comparative studies both treatments seem to be an equal option for the management of these patients. Overall the safety profile of IL-1 inhibitors seems not different in FMF patients than in the other diseases and can be considered as globally safe. The main side effects are local injection site reactions and infections. Conclusion: IL-1 inhibitors have the potential to improve patient outcome even in FMF patients with co-morbidities or severe complications in whom inflammation control is difficult to achieve with colchicine alone. Nevertheless, current data are limited and further evaluation of long-term efficacy and safety of IL-1 inhibitors are necessary, in order to provide robust evidence in this domain.

COVID-19 in patients with familial Mediterranean fever treated with colchicine: case based review

“…Familial Mediterranean fever is the most common monogenic autoinflammatory disease that is characterized by repeated attacks of fever and serositis [ 7 ]. Outbreak of COVID-19 led to a considerable interest in the use of traditional disease-modifying anti-rheumatic drugs (DMARDs), which are considered to be the best prophylactic drugs in FMF [ 6 , 8 , 9 ].…”

Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review

“…Avoidance of precipitating factorssuch as cold exposure, strenuous exercise, certain drugs, and certain foods -might reduce the frequency of attacks. A prospective observation period of three to six months to confirm attacks and determine inciting factors is recommended before the use of biologic drugs [108].…”

“…Three IL-1 antagonists have been studied in the treatment of crFMF: anakinra, canakinumab, and rilonacept. All of the IL-1 antagonists significantly reduce the number of attacks and improve quality of life with good safety profiles [108,109]. Good quality studies are scarce for the use of IL-1 antagonists and all randomized or open label studies included relatively small numbers of patients.…”

“…Anakinra, a recombinant IL-1 receptor antagonist (rHIL-1Ra), was the first IL-1 blocking biologic agent produced and inhibits binding of both IL-1α and IL-1β to the IL-1 receptor. It is the most extensively used IL-1 blocker in FMF treatment and, currently, the cheapest one [108]. Anakinra was studied in only one RCT included 25 FMF patients (12 in anakinra and 13 in placebo arms).…”

“…However, some of the successful reported treatments are disclosed in Table 3. Interestingly, some of the inflammatory comorbid conditions in the course of FMF may also respond well to IL-1 inhibitors, such as spondyloarthritis, Behçet's disease, inflammatory bowel disease, protracted febrile myalgia, hidradenitis suppurativa, pustular psoriasis, and HSP [108].…”