Autoinflammatory diseases (AIDs) represent a rare and heterogeneous group of disorders characterized by recurrent episodes of inflammation and a broad range of clinical manifestations. The most common symptoms involve recurrent fevers, musculoskeletal symptoms, and serositis; however, AIDs can also lead to life-threatening complications, such as macrophage activation syndrome (MAS) and systemic AA amyloidosis. Typical monogenic periodic fever syndromes include cryopyrin-associated periodic fever syndrome (CAPS), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyper IgD syndrome (MKD/HIDS), and familial Mediterranean fever (FMF). However, a number of other clinical entities, such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease (AOSD), Kawasaki disease (KD) and idiopathic recurrent pericarditis (IRP), display similar phenotypical and immunological features to AIDs. All these diseases are pathophysiologicaly characterized by dysregulation of the innate immune system and the central pathogenic role is attributed to the IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, and IL-33). Therefore, reasonable therapeutic approaches aim to inhibit these cytokines and their pathways. To date, several anti-IL-1 therapies have evolved. Each drug differs in structure, mechanism of action, efficacy for the treatment of selected diseases, and side effects. Most of the available data regarding the efficacy and safety of IL-1 inhibitors are related to anakinra, canakinumab, and rilonacept. Other promising therapeutics, such as gevokizumab, tadekinig alfa, and tranilast are currently undergoing clinical trials. In this review, we provide sophisticated and up-to-date insight into the therapeutic uses of different IL-1 inhibitors in monogenic periodic fever syndromes.

Department of Clinical Immunology and Allergology Institute for Clinical and Experimental Medicine Prague Czechia

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czechia

Department of Paediatric and Adult Rheumatology University Hospital Motol Prague Czechia

Zobrazit více v PubMed

Georgin-Lavialle S, Fayand A, Rodrigues F, Bachmeyer C, Savey L, Grateau G. Autoinflammatory diseases: State of the art. Presse Med (2019) 48(1 Pt 2):e25–48.  10.1016/j.lpm.2018.12.003 PubMed DOI

Cantarini L, Vitale A, Lucherini OM, De Clemente C, Caso F, Costa L, et al. The labyrinth of autoinflammatory disorders: a snapshot on the activity of a third-level center in Italy. Clin Rheumatol (2015) 34(1):17–28.  10.1007/s10067-014-2721-0 PubMed DOI

Cattalini M, Soliani M, Lopalco G, Rigante D, Cantarini L. Systemic and organ involvement in monogenic autoinflammatory disorders: a global review filtered through internists’ lens. Intern Emerg Med (2016) 11(6):781–91.  10.1007/s11739-016-1466-y PubMed DOI

Obici L, Merlini G. Amyloidosis in autoinflammatory syndromes. Autoimmun Rev (2012) 12(1):14–7.  10.1016/j.autrev.2012.07.016 PubMed DOI

Cantarini L, Lopalco G, Selmi C, Napodano S, De Rosa G, Caso F, et al. Autoimmunity and autoinflammation as the yin and yang of idiopathic recurrent acute pericarditis. Autoimmun Rev (2015) 14(2):90–7.  10.1016/j.autrev.2014.10.005 PubMed DOI

Cimaz R. Systemic-onset juvenile idiopathic arthritis. Autoimmun Rev (2016) 15(9):931–4.  10.1016/j.autrev.2016.07.004 PubMed DOI

Lee JJY, Schneider R. Systemic Juvenile Idiopathic Arthritis. Pediatr Clin North Am (2018) 65(4):691–709.  10.1016/j.pcl.2018.04.005 PubMed DOI

Patel RM, Shulman ST. Kawasaki disease: a comprehensive review of treatment options. J Clin Pharm Ther (2015) 40(6):620–5.  10.1111/jcpt.12334 PubMed DOI

US National Library of Medicine ClinicalTrials. Available at: https://clinicaltrials.gov [Accessed September 30, 2020].

Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev (2018) 281(1):8–27.  10.1111/imr.12621 PubMed DOI PMC

Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol (2019) 15(10):612–32.  10.1038/s41584-019-0277-8 PubMed DOI

Striz I. Cytokines of the IL-1 family: recognized targets in chronic inflammation underrated in organ transplantations. Clin Sci (Lond) (2017) 131(17):2241–56.  10.1042/CS20170098 PubMed DOI

Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood (2011) 117(14):3720–32.  10.1182/blood-2010-07-273417 PubMed DOI PMC

European Medicines Agency Summary of Product Characteristics—Kineret Available at: https://www.ema.europa.eu/documents/product-information/kineret-epar-product-information_en.pdf (Accessed 8 March 2019).

European Medicines Agency Summary of Product Characteristics—Ilaris Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/ilaris (Accessed 17 April 2019).

Junge G, Mason J, Feist E. Adult onset Still’s disease-The evidence that anti-interleukin-1 treatment is effective and well-tolerated (a comprehensive literature review). Semin Arthritis Rheum (2017) 47(2):295–302.  10.1016/j.semarthrit.2017.06.006 PubMed DOI

Tarp S, Amarilyo G, Foeldvari I, Christensen R, Woo JM, Cohen N, et al. Efficacy and safety of biological agents for systemic juvenile idiopathic arthritis: a systematic review and meta-analysis of randomized trials. Rheumatol (Oxford) (2016) 55(4):669–79.  10.1093/rheumatology/kev382 PubMed DOI PMC

Owyang AM, Issafras H, Corbin J, Ahluwalia K, Larsen P, Pongo E, et al. XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1beta-mediated diseases. MAbs (2011) 3(1):49–60.  10.4161/mabs.3.1.13989 PubMed DOI PMC

Gabay C, Fautrel B, Rech J, Spertini F, Feist E, Kotter I, et al. Open-label, multicentre, dose-escalating phase II clinical trial on the safety and efficacy of tadekinig alfa (IL-18BP) in adult-onset Still’s disease. Ann Rheum Dis (2018) 77(6):840–7.  10.1136/annrheumdis-2017-212608 PubMed DOI PMC

Huang Y, Jiang H, Chen Y, Wang X, Yang Y, Tao J, et al. Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol Med (2018) 10(4):1–15.  10.15252/emmm.201708689 PubMed DOI PMC

Kluck V, Jansen T, Janssen M, Comarniceanu A, Efde M, Tengesdal IW, et al. Dapansutrile, an oral selective NLRP3 inflammasome inhibitor, for treatment of gout flares: an open-label, dose-adaptive, proof-of-concept, phase 2a trial. Lancet Rheumatol (2020) 2(5):e270–80.  10.1016/S2665-9913(20)30065-5 PubMed DOI PMC

Sanchez-Fernandez A, Skouras DB, Dinarello CA, López-Vales R. OLT1177 (Dapansutrile), a Selective NLRP3 Inflammasome Inhibitor, Ameliorates Experimental Autoimmune Encephalomyelitis Pathogenesis. Front Immunol (2019) 10:2578.  10.3389/fimmu.2019.02578 PubMed DOI PMC

Caseley EA, Poulter JA, Rodrigues F., Immunome Project Consortium for Autoinflammatory D. McDermott MF. Inflammasome inhibition under physiological and pharmacological conditions. Genes Immun (2020) 21(4):211–23.  10.1038/s41435-020-0104-x PubMed DOI

La Manna S, Di Natale C, Florio D, Marasco D. Peptides as Therapeutic Agents for Inflammatory-Related Diseases. Int J Mol Sci (2018) 19(9):1–18.  10.3390/ijms19092714 PubMed DOI PMC

McKee CM, Coll RC. NLRP3 inflammasome priming: A riddle wrapped in a mystery inside an enigma. J Leukoc Biol (2020) 108(3):937–52.  10.1002/JLB.3MR0720-513R PubMed DOI

Goldbach-Mansky R, Dailey NJ, Canna SW, Gelabert A, Jones J, Rubin BI, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med (2006) 355(6):581–92. 10.1056/NEJMoa055137 PubMed DOI PMC

Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, Wittkowski H, Bialkowski A, Tzaribachev N, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum (2011) 63(3):840–9.  10.1002/art.30149 PubMed DOI

Kullenberg T, Löfqvist M, Leinonen M, Goldbach-Mansky R, Olivecrona H. Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes. Rheumatol (Oxford) (2016) 55(8):1499–506.  10.1093/rheumatology/kew208 PubMed DOI PMC

Kuemmerle-Deschner JB, Ramos E, Blank N, Roesler J, Felix SD, Jung T, et al. Canakinumab (ACZ885, a fully human IgG1 anti-IL-1beta mAb) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS). Arthritis Res Ther (2011) 13(1):R34.  10.1186/ar3266 PubMed DOI PMC

Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, et al. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis (2011) 70(12):2095–102.  10.1136/ard.2011.152728 PubMed DOI

Kuemmerle-Deschner JB, Wittkowski H, Tyrrell PN, Koetter I, Lohse P, Ummenhofer K, et al. Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther (2013) 15(3):R64.  10.1186/ar4237 PubMed DOI PMC

Sibley CH, Chioato A, Felix S, Colin L, Chakraborty A, Plass N, et al. A 24-month open-label study of canakinumab in neonatal-onset multisystem inflammatory disease. Ann Rheum Dis (2015) 74(9):1714–9.  10.1136/annrheumdis-2013-204877 PubMed DOI PMC

Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum (2008) 58(8):2443–52.  10.1002/art.23687 PubMed DOI

Kone-Paut I, Lachmann HJ, Kuemmerle-Deschner JB, Hachulla E, Leslie KS, Mouy R, et al. Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study. Arthritis Res Ther (2011) 13(6):R202.  10.1186/ar3535 PubMed DOI PMC

Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med (2009) 360(23):2416–25.  10.1056/NEJMoa0810787 PubMed DOI

Gattorno M, Pelagatti MA, Meini A, Obici L, Barcellona R, Federici S, et al. Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum (2008) 58(5):1516–20.  10.1002/art.23475 PubMed DOI

Gattorno M, Obici L, Cattalini M, Tormey V, Abrams K, Davis N, et al. Canakinumab treatment for patients with active recurrent or chronic TNF receptor-associated periodic syndrome (TRAPS): an open-label, phase II study. Ann Rheum Dis (2017) 76(1):173–8.  10.1136/annrheumdis-2015-209031 PubMed DOI PMC

Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum (2001) 44(6):1416–9.  10.1002/1529-0131(200106)44:6<1416::AID-ART236>3.0.CO;2-6 PubMed DOI

Brik R, Butbul-Aviel Y, Lubin S, Dayan EB, Rachmilewitz-Minei T, Tseng L, et al. Canakinumab for the treatment of children with colchicine-resistant familial Mediterranean fever: a 6-month open-label, single-arm pilot study. Arthritis Rheumatol (2014) 66(11):3241–3.  10.1002/art.38777 PubMed DOI

Gul A, Ozdogan H, Erer B, Ugurlu S, Kasapcopur O, Davis N, et al. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever. Arthritis Res Ther (2015) 17:243.  10.1186/s13075-015-0765-4 PubMed DOI PMC

Basaran O, Uncu N, Çelikel BA, Taktak A, Gür G, Cakar N. Interleukin-1 targeting treatment in familial Mediterranean fever: an experience of pediatric patients. Mod Rheumatol (2015) 25(4):621–4.  10.3109/14397595.2014.987437 PubMed DOI

Cetin P, Sari I, Sozeri B, Cam O, Birlik M, Akkoc N, et al. Efficacy of interleukin-1 targeting treatments in patients with familial mediterranean Fever. Inflammation (2015) 38(1):27–31.  10.1007/s10753-014-0004-1 PubMed DOI

Gulez N, Makay B, Sozeri B. Long-term effectiveness and safety of canakinumab in pediatric familial Mediterranean fever patients. Mod Rheumatol (2020) 30(1):166–71.  10.1080/14397595.2018.1559488 PubMed DOI

Ozcakar ZB, Özdel S, Yılmaz S, Kurt-Şükür ED, Ekim M, Yalçınkaya F. Anti-IL-1 treatment in familial Mediterranean fever and related amyloidosis. Clin Rheumatol (2016) 35(2):441–6.  10.1007/s10067-014-2772-2 PubMed DOI

Kuemmerle-Deschner JB, Gautam R, George AT, Raza S, Lomax KG, Hur P. A systematic literature review of efficacy, effectiveness and safety of biologic therapies for treatment of familial Mediterranean fever. Rheumatol (Oxford) (2020) 59(10):2711–24.  10.1093/rheumatology/keaa205 PubMed DOI

Ozen S, Ben-Cherit E, Foeldvari I, Amarilyo G, Ozdogan H, Vanderschueren S, et al. Long-term efficacy and safety of canakinumab in patients with colchicine-resistant familial Mediterranean fever: results from the randomised phase III CLUSTER trial. Ann Rheum Dis (2020) 79(10):1362–9.  10.1136/annrheumdis-2020-217419 PubMed DOI PMC

Eroglu FK, Beşbaş N, Topaloglu R, Ozen S. Treatment of colchicine-resistant Familial Mediterranean fever in children and adolescents. Rheumatol Int (2015) 35(10):1733–7.  10.1007/s00296-015-3293-2 PubMed DOI

Kurt T, Aydın F, Tekgöz PN, Sezer M, Uncu N, Acar BÇ. Effect of anti-interleukin-1 treatment on quality of life in children with colchicine-resistant familial Mediterranean fever: A single-center experience. Int J Rheum Dis (2020) 23(7):977–81.  10.1111/1756-185X.13891 PubMed DOI

Hashkes PJ, Spalding SJ, Giannini EH, Huang B, Johnson A, Park G, et al. Rilonacept for colchicine-resistant or -intolerant familial Mediterranean fever: a randomized trial. Ann Intern Med (2012) 157(8):533–41.  10.7326/0003-4819-157-8-201210160-00003 PubMed DOI

Ben-Zvi I, Giat E, Pras E, Feld O, Kivity S, et al. Anakinra for Colchicine-Resistant Familial Mediterranean Fever: A Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol (2017) 69(4):854–62.  10.1002/art.39995 PubMed DOI

Ter Haar NM, Jeyaratnam J, Lachmann HJ, Simon A, Brogan PA, Doglio M, et al. The Phenotype and Genotype of Mevalonate Kinase Deficiency: A Series of 114 Cases From the Eurofever Registry. Arthritis Rheumatol (2016) 68(11):2795–805.  10.1002/art.39763 PubMed DOI

Bodar EJ, Kuijk LM, Drenth JPH, van der Meer JWM, Simon A, Frenkel J. On-demand anakinra treatment is effective in mevalonate kinase deficiency. Ann Rheum Dis (2011) 70(12):2155–8.  10.1136/ard.2011.149922 PubMed DOI

Arostegui JI, Anton J, Calvo I, Robles A, Iglesias E, Lopez-Montesinos B, et al. Open-Label, Phase II Study to Assess the Efficacy and Safety of Canakinumab Treatment in Active Hyperimmunoglobulinemia D With Periodic Fever Syndrome. Arthritis Rheumatol (2017) 69(8):1679–88.  10.1002/art.40146 PubMed DOI

Tanaka T, Yoshioka K, Nishikomori R, Sakai H, Abe J, Yamashita Y, et al. National survey of Japanese patients with mevalonate kinase deficiency reveals distinctive genetic and clinical characteristics. Mod Rheumatol (2019) 29(1):181–7.  10.1080/14397595.2018.1442639 PubMed DOI

De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM, et al. Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med (2018) 378(20):1908–19.  10.1056/NEJMoa1706314 PubMed DOI

van der Hilst JC, Bodar EJ, Barron KS, Frenkel J, Drenth JPH, van der Meer JWM, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Med (Baltimore) (2008) 87(6):301–10.  10.1097/MD.0b013e318190cfb7 PubMed DOI

Gasparyan AY, Ayvazyan L, Blackmore H, Kitas GD. Writing a narrative biomedical review: considerations for authors, peer reviewers, and editors. Rheumatol Int (2011) 31(11):1409–17.  10.1007/s00296-011-1999-3 PubMed DOI

Hoffman HM, Wanderer AA, Broide DH. Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal dominant periodic fever. J Allergy Clin Immunol (2001) 108(4):615–20.  10.1067/mai.2001.118790 PubMed DOI PMC

Kuemmerle-Deschner JB, Samba SD, Tyrrell PN, Koné-Paut I, Marie I, Deschner N, et al. Challenges in diagnosing Muckle-Wells syndrome: identifying two distinct phenotypes. Arthritis Care Res (Hoboken) (2014) 66(5):765–72.  10.1002/acr.22206 PubMed DOI

Tran TA. Muckle-Wells syndrome: clinical perspectives. Open Access Rheumatol (2017) 9:123–9.  10.2147/OARRR.S114447 PubMed DOI PMC

Finetti M, Omenetti A, Federici S, Caorsi R, Gattorno M. Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome: a review. Orphanet J Rare Dis (2016) 11(1):167.  10.1186/s13023-016-0542-8 PubMed DOI PMC

Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, et al. Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis (2019) 78(8):1025–32. 10.1136/annrheumdis-2019-215048 PubMed DOI

Cantarini L, Lucherini OM, Frediani B, Brizi MG, Bartolomei B, Cimaz R, et al. Bridging the gap between the clinician and the patient with cryopyrin-associated periodic syndromes. Int J Immunopathol Pharmacol (2011) 24(4):827–36.  10.1177/039463201102400402 PubMed DOI

ter Haar NM, Oswald M, Jeyaratnam J, Anton J, Barron KS, Brogan PA, et al. Recommendations for the management of autoinflammatory diseases. Ann Rheum Dis (2015) 74(9):1636–44. 10.1136/annrheumdis-2015-207546 PubMed DOI

Hawkins PN, Lachmann HJ, McDermott MF. Interleukin-1-receptor antagonist in the Muckle-Wells syndrome. N Engl J Med (2003) 348(25):2583–4.  10.1056/NEJM200306193482523 PubMed DOI

Caroli F, Pontillo A, D'Osualdo A, Travan L, Ceccherini I, Crovella S, et al. Clinical and genetic characterization of Italian patients affected by CINCA syndrome. Rheumatol (Oxford) (2007) 46(3):473–8.  10.1093/rheumatology/kel269 PubMed DOI

Dalgic B, et al. A variant Muckle-Wells syndrome with a novel mutation in CIAS1 gene responding to anakinra. Pediatr Nephrol (2007) 22(9):1391–4.  10.1007/s00467-007-0500-8 PubMed DOI

Maksimovic L, et al. New CIAS1 mutation and anakinra efficacy in overlapping of Muckle-Wells and familial cold autoinflammatory syndromes. Rheumatol (Oxford) (2008) 47(3):309–10.  10.1093/rheumatology/kem318 PubMed DOI

Marchica C, et al. Resolution of unilateral sensorineural hearing loss in a pediatric patient with a severe phenotype of Muckle-Wells syndrome treated with Anakinra: a case report and review of the literature. J Otolaryngol Head Neck Surg (2018) 47(1):9.  10.1186/s40463-018-0256-0 PubMed DOI PMC

Neven B, et al. Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum (2010) 62(1):258–67.  10.1002/art.25057 PubMed DOI

Sibley CH, Plass N, Snow J, Wiggs EA, Brewer CC, King KA, et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum (2012) 64(7):2375–86.  10.1002/art.34409 PubMed DOI PMC

Stew BT, Fishpool SJC, Owens D, Quine S. Muckle-Wells syndrome: a treatable cause of congenital sensorineural hearing loss. B-ENT (2013) 9(2):161–3. PubMed

Yamazaki T, Masumoto J, Agematsu K, Sawai N, Kobayashi S, Shigemura T, et al. Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome. Arthritis Rheum (2008) 58(3):864–8.  10.1002/art.23261 PubMed DOI

Goldbach-Mansky R, et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum (2008) 58(8):2432–42.  10.1002/art.23620 PubMed DOI PMC

Rigante D, Rigante D, Vitale A, Frediani B, Iannone F, Cantarini L. Key facts and hot spots on tumor necrosis factor receptor-associated periodic syndrome. Clin Rheumatol (2014) 33(9):1197–207.  10.1007/s10067-014-2722-z PubMed DOI

Magnotti F, Vitale A, Rigante D, Lucherini OM, Cimaz R, Muscari I, et al. The most recent advances in pathophysiology and management of tumour necrosis factor receptor-associated periodic syndrome (TRAPS): personal experience and literature review. Clin Exp Rheumatol (2013) 31(3 Suppl 77):141–9. PubMed

Cantarini L, Lopalco G, Vitale A, Caso F, Lapadula G, Iannone F, et al. Delights and let-downs in the management of tumor necrosis factor receptor-associated periodic syndrome: the canakinumab experience in a patient with a high-penetrance T50M TNFRSF1A variant. Int J Rheum Dis (2015) 18(4):473–5.  10.1111/1756-185X.12521 PubMed DOI

Lopalco G, Rigante D, Vitale A, Frediani B, Iannone F, Cantarini L. Tumor necrosis factor receptor-associated periodic syndrome managed with the couple canakinumab-alendronate. Clin Rheumatol (2015) 34(4):807–9.  10.1007/s10067-014-2556-8 PubMed DOI

Uthman I, Hajj-Ali RA, Arayssi T, Masri AF, Nasr F. Arthritis in familial Mediterranean fever. Rheumatol Int (2001) 20(4):145–8.  10.1007/s002960100103 PubMed DOI

Alghamdi M. Familial Mediterranean fever, review of the literature. Clin Rheumatol (2017) 36(8):1707–13.  10.1007/s10067-017-3715-5 PubMed DOI

Rigante D, Lopalco G, Tarantino G, Compagnone A, Fastiggi M, Cantarini L. Non-canonical manifestations of familial Mediterranean fever: a changing paradigm. Clin Rheumatol (2015) 34(9):1503–11.  10.1007/s10067-015-2916-z PubMed DOI

Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis (2016) 75(4):644–51.  10.1136/annrheumdis-2015-208690 PubMed DOI

El Hasbani G, Jawad A, Uthman I. Update on the management of colchicine resistant Familial Mediterranean Fever (FMF). Orphanet J Rare Dis (2019) 14(1):224.  10.1186/s13023-019-1201-7 PubMed DOI PMC

Ozen S, Kone-Paut I, Gul A. Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments. Semin Arthritis Rheum (2017) 47(1):115–20.  10.1016/j.semarthrit.2017.03.006 PubMed DOI

Lazaros G, Antonopoulos AS, Antonatou K, Skendros P, Ritis K, Hadziyannis E, et al. Hydroxychloroquine for colchicine-resistant glucocorticoid-dependent idiopathic recurrent pericarditis: A pilot observational prospective study. Int J Cardiol (2020) 311:77–82.  10.1016/j.ijcard.2020.03.069 PubMed DOI

Tombetti E, Mulè A, Tamanini S, Matteucci L, Negro E, Brucato A, et al. Novel Pharmacotherapies for Recurrent Pericarditis: Current Options in 2020. Curr Cardiol Rep (2020) 22(8):59.  10.1007/s11886-020-01308-y PubMed DOI PMC

Laskari K, Boura P, Dalekos GN, Garyfallos A, Karokis D, Pikazis D, et al. Longterm Beneficial Effect of Canakinumab in Colchicine-resistant Familial Mediterranean Fever. J Rheumatol (2017) 44(1):102–9.  10.3899/jrheum.160518 PubMed DOI

Kucuksahin O, Yildizgoren MT, Ilgen U, Ates A, Kinikli G, Turgay M, et al. Anti-interleukin-1 treatment in 26 patients with refractory familial mediterranean fever. Mod Rheumatol (2017) 27(2):350–5.  10.1080/14397595.2016.1194510 PubMed DOI

Cakan M, Karadag SG, Ayaz NA. Canakinumab in colchicine resistant familial Mediterranean fever and other pediatric rheumatic diseases. Turk J Pediatr (2020) 62(2):167–74.  10.24953/turkjped.2020.02.001 PubMed DOI

Sag E, Akal F, Atalay E, Akca UK, Demir S, Demirel D, et al. Anti-IL1 treatment in colchicine-resistant paediatric FMF patients: real life data from the HELIOS registry. Rheumatol (Oxford) (2020) 59(11):3324–9.  10.1093/rheumatology/keaa121 PubMed DOI

Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet (1999) 22(2):175–7.  10.1038/9691 PubMed DOI

Galeotti C, Meinzer U, Quartier P, Rossi-Semerano L, Bader-Meunier B, Pillet P, et al. Efficacy of interleukin-1-targeting drugs in mevalonate kinase deficiency. Rheumatol (Oxford) (2012) 51(10):1855–9.  10.1093/rheumatology/kes097 PubMed DOI

Ter Haar N, Lachmann H, Ozen S, Woo P, Uziel Y, Modesto C, et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis (2013) 72(5):678–85.  10.1136/annrheumdis-2011-201268 PubMed DOI