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The right place of interleukin-1 inhibitors in the treatment of Behçet’s syndrome: a systematic review

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Abstract

Behçet’s syndrome (BS) is a chronic (auto)-inflammatory disorder characterized by different clusters of symptoms, including mucocutaneous and ocular involvements. Interleukin-1 inhibitors anakinra (ANA), canakinumab (CAN), and gevokizumab (GEV) represent a promising therapeutic alternative in BS. To date, evidence on the use of ANA, CAN, and GEV is mainly based on small isolated studies or case series, and the real place of anti-IL1 agents in the treatment of BS is still unclear. We performed a systematic review of current evidence on the efficacy and safety of anti-IL1 agents in BS. The PubMed search yielded a total of 398 references, from which we retrieved 24 studies for inclusion (4 clinical trials, 6 observational studies, 14 case reports, case series or letters to the editor). Four studies evaluated the overall efficacy of IL-1 inhibitors, 15 studies focused on the specific efficacy of ANA, whereas efficacy of CAN and GEV was evaluated in 8 and 3 studies, respectively. Both ANA and CAN were associated with good control of mucocutaneous and ocular manifestations. ANA resulted effective also for osteoarticular manifestations. GEV was studied only for ocular manifestations, but gave contrasting results. Discordant evidence supports the use of ANA and CAN in pediatric setting and for first-line treatment of general BS manifestations. Most frequent side effects were local or diffuse cutaneous reactions and injection site reactions, particularly for ANA treatment. Blocking the IL-1 pathway could be an effective therapeutic strategy in particular BS involvements.

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Acknowledgements

The authors wish to thank Stefano Salvati and Javier Hernández Plasencia for their help in preparing the Fig. 2.

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This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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  1. Alessandra Soriano, Giacomo Emmi are joint senior authors.

Authors and Affiliations

  1. Department of Neuroscience Psychology, Drug Research and Child Health (NEUROFARBA), University of Firenze, Florence, Italy

    Alessandra Bettiol

  2. Department of Experimental and Clinical Medicine, University of Firenze, Florence, Italy

    Elena Silvestri, Gerardo Di Scala, Amedeo Amedei & Giacomo Emmi

  3. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Firenze, Florence, Italy

    Matteo Becatti & Claudia Fiorillo

  4. Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Bari, Italy

    Giuseppe Lopalco

  5. Rheumatology Unit, Istituto di Ricovero e Cura a CarattereScientifico, Reggio Emilia, Azienda USL di Reggio Emilia, Università di Modena e Reggio Emilia, Modena, Italy

    Carlo Salvarani & Alessandra Soriano

  6. Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy

    Luca Cantarini

  7. Center for Rare Immunological and Cardiovascular Diseases, Behçet Centre and Lupus Clinic, AOU Careggi, Largo Brambilla 3, 50134, Florence, Italy

    Giacomo Emmi

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  1. Alessandra Bettiol
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Contributions

All authors contributed to the conception of the work. Authors AB and GE contributed to the design of the work and in the acquisition and analysis of data. Authors ES, GDS, GL, CS, LC, AS, and GE contributed in the interpretation of data for the work. Authors AB and GE contributed in drafting the work, and all other authors revised it critically for important intellectual content. All authors approved the final version of the manuscript to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Giacomo Emmi.

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LC received research grant and participated at speaker’s bureau by Sobi and Novartis. GE received fee from SOBI for consultancy and participated at speaker’s bureau by Novartis. AS received fee from SOBI for consultancy. All other authors declare that they have no conflict of interest.

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Bettiol, A., Silvestri, E., Di Scala, G. et al. The right place of interleukin-1 inhibitors in the treatment of Behçet’s syndrome: a systematic review. Rheumatol Int 39, 971–990 (2019). https://doi.org/10.1007/s00296-019-04259-y

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