Could tocilizumab be used in familial Mediterranean fever? A systematic review

First author : P. Mertz

Review: Rheumatology

Link to article: https://doi.org/10.1093/rheumatology/keae338

Could tocilizumab be used in Familial Mediterranean Fever ?

Abstract:

Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as IL-1β, TNF-α and IL-6 inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.

Results:

After selection, 14 articles were included: two double-blind RCTs, two retrospective studies and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in paediatric FMF.

Conclusion:

This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Could tocilizumab be used in familial Mediterranean fever?.pdf

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Characteristics of familial Mediterranean fever after 65 years of age

First author: François Rodrigues et al.

Link to article: https://doi.org/10.1016/j.ejim.2024.10.010

              Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in MEFV, characterized by recurrent febrile attacks. The natural history of the disease, which began in children and had a high mortality rate in the last century, is unknown in people over 65.

        This retrospective study included the records of 59 patients with FMF followed at Hôpital Tenon (Paris, France), representing 9% of the total number of patients followed for FMF. The median age was 73 years. Although all patients were treated with colchicine, the study population, born in the 1940s-1950s, had a late diagnosis (median age 28 years) and a delayed initiation of colchicine (35 years, median year of introduction 1980). 73% of patients had an elevated intercritical CRP on colchicine, and 37% had to receive an inteleukin-1 inhibitor, with good tolerability. The prevalence of AA amyloidosis was 10%. The most frequent comorbidities were cardiovascular (59% of patients) and, unexpectedly, hepatic (37%), with a high frequency of non-alcoholic, non-viral cirrhosis (27%) and no associated diabetes, suggesting a link with FMF. Nine patients (15%) had died at the time of collection, two from complications of FMF, two from hepatic cirrhosis, and five from infections.

             In conclusion, the study indicates that FMF can remain active after the age of 65, motivating specialized lifelong follow-up with CRP monitoring between attacks, as well as the prescription of biotherapy in the event of unsatisfactory disease control.

Caractéristiques de la fièvre méditerranéenne familiale après 65 ans.pdf

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National Protocol for Diagnosis and Care of Familial Mediterranean Fever

S. Georgin-Laviallea,h,∗, L. Saveya,h, L. Cuissetc, G. Boursiere,h, J.-J. Boffab,h,

M. Delplanquea,h, R. Bourguibaa,h, J.-B. Monfortd,h, I. Touitoue,h, G. Grateaua,h,

I. Kone-Pautf,h, V. Hentgeng,h, Collaborators1

Summary:

Familial Mediterranean Fever is the world's most common monogenic autoinflammatory disease. It mainly affects people from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood, associated with abdominal and/or thoracic pain lasting an average of 2 to 3 days, and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis of large joints such as the knees and ankles, myalgia of the lower limbs and pseudo-eryzipelas of the ankles. Its most severe complication is inflammatory amyloidosis, or AA amyloidosis, which can lead to renal failure. Treatment is based on colchicine, which helps prevent relapses and the onset of renal amyloidosis.

This work presents national recommendations for the diagnosis, management and follow-up of Familial Mediterranean Fever in France, where we estimate there are between 5,000 and 10,000 patients with the disease at all stages of life. Diagnosis is suspected on the basis of clinical and anamnestic elements, and confirmed by genetic analysis. These recommendations also propose a “treat-to-target” approach to disease treatment, particularly in cases of suspected colchicine resistance - a very rare situation that should remain a situation of elimination, particularly after verification of colchicine compliance. Two special situations are also addressed in these recommendations: renal failure and pregnancy.

​© 2023 Publié par Elsevier Masson SAS au nom de Société Nationale Franc¸ aise de Médecine Interne (SNFMI).

French recommandation for the diagnostic and care of FMF Rev Med int.pdf

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