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

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?

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An update on autoinflammatory diseases

First author: S. Georgin-Lavialle

Abstract:

Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases, due to the absence of involvement of the adaptive immune system and circulating autoantibodies. The 4 IADs first described are known as the “historic” IADs and include: familial Mediterranean fever (associated with mutations in the MEFV gene), cryopyrinopathies (associated with mutations in NLRP3), tumor necrosis factor receptor-associated periodic syndrome (associated with mutations in TNFRSF1A) and mevalonate kinase deficiency (associated with mutations in MVK). Over the past 10 years, more than 50 new monogenic IBDs have been discovered thanks to advances in genetics. Diagnosis is facilitated by personal and family history-taking and detailed analysis of the signs and symptoms associated with febrile attacks, which must be associated with the presence of elevated blood biomarkers of inflammation. Increasingly powerful genetic analysis techniques can help refine the diagnosis. This chapter describes the main types of IJD, and helps to guide the clinician in the suspicion and diagnosis of IJD.

MAi en français

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Break down the barriers of auto-inflammation:How to deal with a monogenic auto-inflammatorydisease and immuno-haematological features in 2022?

First author : Hélène Vergneault

Review: Immunology

Link to article: DOI: 10.1111/imm.13579

Principales caractéristiques immuno-hématologiques en fonction du principal mécanisme physiopathologique impliqué.

Abstract:

In the past few years, the spectrum of monogenic systemic auto-inflammatory diseases (MSAID) has widely expanded beyond the typical recurrent fever. Immunohaematological features, as cytopenias, hypogammaglobulinemia, hypereosinophilia,lymphoproliferation and immunodeficiency, have been described in association of several MSAID. The objective of this review was to describe these particular MSAID. MSAID must be suspected in front of immuno-haematological features associated with non-infectious recurrent fever, chronic systemic inflammation, inflammatory cutaneous manifestations, arthritis or inflammatory bowel disease. Genes and cellular mechanisms involved are various but some of them are of special interest. Defects in actine regulation pathway are notably associated with cytopenia and immune deficiency. Because of their frequency, ADA2 deficiency and Vacuoles, E1-Enzyme, X-linked, auto-inflammatory, Somatic (VEXAS) syndrome deserve to be noticed. ADA2 deficiency results in polyarteritis nodosalike presentation with a wide panel of manifestations including cytopenia(s), lymphoproliferation and immune deficiency. Neutrophilic dermatosis or chondritis associated with macrocytic anaemia or myelodysplasia should lead to screen for VEXAS. Of note, most of MSAID are associated with inflammatory anaemia. We proposed here a clinical and pragmatic approach of MSAID associated with immuno-haematological features.

Vergneault - Break down the barriers of auto‐inflammation How to deal with a monogenic AI

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