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Review
. 2020 Jun 3:11:865.
doi: 10.3389/fimmu.2020.00865. eCollection 2020.

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide

Alessandra Soriano  1 , Marco Soriano  2 , Gerard Espinosa  3 , Raffaele Manna  4 , Giacomo Emmi  5 , Luca Cantarini  6 , José Hernández-Rodríguez  3
Affiliations
Review

Current Therapeutic Options for the Main Monogenic Autoinflammatory Diseases and PFAPA Syndrome: Evidence-Based Approach and Proposal of a Practical Guide

Alessandra Soriano et al. Front Immunol. .

Abstract

Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly based on results from retrospective studies and physicians' experience. However, during the last years, the significant improvement in their genetic and pathogenic knowledge has been accompanied by a remarkable progress in their management. The relatively recent identification of the inflammasome as the crucial pathogenic mechanism causing an aberrant production of interleukin 1β (IL-1β) in the most frequent monogenic autoinflammatory diseases led to the introduction of anti-IL-1 agents and other biologic drugs as part of the previously limited therapeutic armamentarium available. Advances in the treatment of autoinflammatory diseases have been favored by the use of new biologic agents and the performance of a notable number of randomized clinical trials exploring the efficacy and safety of these agents. Clinical trials have contributed to increase the level of evidence and provided more robust therapeutic recommendations. This review analyzes the treatment of the most frequent monogenic autoinflammatory diseases, namely, familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and cryopyrin-associated periodic syndromes, together with periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, which is the most common polygenic autoinflammatory disease in children, also occurring in adult patients. Finally, based on the available expert consensus recommendations and the highest level of evidence of the published studies, a practical evidence-based guideline for the treatment of these autoinflammatory diseases is proposed.

Keywords: Janus kinase (JAK) inhibitors; PFAPA syndrome; anakinra; anti-TNF agents; canakinumab; colchicine; monogenic autoinflammatory diseases; tocilizumab.

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Figures

Figure 1
Figure 1
Proposed approach for the treatment of the main monogenic autoinflammatory diseases and PFAPA syndrome, based on the maximum level of evidence and grade of recommendation (when available) for each drug and disease. No strength of recommendation is provided when expert opinion consensus still does not exist. Thalidomide and dapsone have also been reported of benefit in some colchicine-resistant FMF patients (data within the text). *This drug has been proved effective with continuous and on demand administration. **This drug is recommended mostly in short courses (on demand) during attacks. ¦Colchicine in PFAPA patients has been reported more effective in carriers of heterozygous variants in the MEFV gene. §Anti-TNF agents (etanercept, infliximab, and adalimumab) have been shown more useful in FMF patients with prominent articular manifestations. #Tocilizumab has been used with efficacy in few patients with FMF, TRAPS, and HIDS/MKD who failed to anti–IL-1 and/or anti-TNF agents. #Tofacitinib has shown good response in few patients with colchicine-resistant FMF who also failed to IL-1, TNF, and IL-6 blockers. CAPS, cryopyrin-associated periodic syndrome; FMF, familial Mediterranean fever; HIDS/MKD, hyperimmunoglobulin D and periodic fever syndrome/mevalonate kinase deficiency; PFAPA, periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis; TRAPS, TNF receptor–associated periodic syndrome.
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