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25.02.2019 | Systematic Review

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

verfasst von: Alessandra Bettiol, Elena Silvestri, Gerardo Di Scala, Amedeo Amedei, Matteo Becatti, Claudia Fiorillo, Giuseppe Lopalco, Carlo Salvarani, Luca Cantarini, Alessandra Soriano, Giacomo Emmi

Erschienen in: Rheumatology International | Ausgabe 6/2019

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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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Emmi G, Silvestri E, Squatrito D et al (2014) Behçet’s syndrome pathophysiology and potential therapeutic targets. Intern Emerg Med 9:257–265. https://doi.org/10.1007/s11739-013-1036-5 CrossRefPubMed

Morton LT, Situnayake D, Wallace GR (2016) Genetics of Behçetʼs disease. Curr Opin Rheumatol 28:39–44. https://doi.org/10.1097/BOR.0000000000000234 CrossRefPubMed

Consolandi C, Turroni S, Emmi G et al (2015) Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 14:269–276. https://doi.org/10.1016/j.autrev.2014.11.009 CrossRefPubMed

Volle G, Fraison J-B, Gobert D et al (2017) Dietary and nondietary triggers of oral ulcer recurrences in Behçet’s disease. Arthritis Care Res (Hoboken) 69:1429–1436. https://doi.org/10.1002/acr.23155 CrossRef

Becatti M, Emmi G, Silvestri E et al (2016) Neutrophil activation promotes fibrinogen oxidation and thrombus formation in Behçet disease. Circulation 133:302–311. https://doi.org/10.1161/CIRCULATIONAHA.115.017738 CrossRefPubMed

Emmi G, Silvestri E, Bella C, Della et al (2016) Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. Medicine (Baltimore) 95:e5516. https://doi.org/10.1097/MD.0000000000005516 CrossRef

Aldinucci A, Bonechi E, Biagioli T et al (2018) CSF/serum matrix metallopeptidase-9 ratio discriminates neuro Behçet from multiple sclerosis. Ann Clin Transl Neurol 5:493–498. https://doi.org/10.1002/acn3.538 CrossRefPubMedPubMedCentral

Akkoç N (2018) Update on the epidemiology, risk factors and disease outcomes of Behçet’s disease. Best Pract Res Clin Rheumatol 32:261–270. https://doi.org/10.1016/j.berh.2018.08.010 CrossRefPubMed

Nanke Y, Yago T, Kotake S (2017) The role of Th17 cells in the pathogenesis of Behcet’s disease. J Clin Med 6:74. https://doi.org/10.3390/jcm6070074 CrossRefPubMedCentral

10.

Kirino Y, Nakajima H (2019) Clinical and genetic aspects of Behçet’s disease in Japan. Intern Med. https://doi.org/10.2169/internalmedicine.2035-18 CrossRefPubMedPubMedCentral

11.

Hatemi G, Seyahi E, Fresko I et al Behçet’s syndrome: a critical digest of the 2013–2014 literature. Clin Exp Rheumatol 32:S112-22

12.

Hatemi G, Christensen R, Bang D et al (2018) 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis 77:808–818. https://doi.org/10.1136/annrheumdis-2018-213225 CrossRefPubMed

13.

Emmi G, Vitale A, Silvestri E et al (2018) Adalimumab-based treatment versus DMARDs for venous thrombosis in Behçet syndrome. A retrospective study of 70 patients with vascular involvement. Arthritis Rheumatol. https://doi.org/10.1002/art.40531 CrossRefPubMed

14.

Lopalco G, Emmi G, Gentileschi S et al (2017) Certolizumab Pegol treatment in Behcet’s disease with different organ involvement: A multicenter retrospective observational study. Mod Rheumatol 27:1031–1035. https://doi.org/10.1080/14397595.2017.1285857 CrossRefPubMed

15.

Urruticoechea-Arana A, Cobo-Ibáñez T, Villaverde-García V et al (2019) Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behçet’s disease associated uveitis: a systematic review. Rheumatol Int 39:47–58. https://doi.org/10.1007/s00296-018-4193-z CrossRefPubMed

16.

Vitale A, Emmi G, Lopalco G et al (2017) Adalimumab effectiveness in Behçet’s disease: short and long-term data from a multicenter retrospective observational study. Clin Rheumatol 36:451–455. https://doi.org/10.1007/s10067-016-3417-4 CrossRefPubMed

17.

Fabiani C, Vitale A, Emmi G et al (2017) Efficacy and safety of adalimumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36:183–189. https://doi.org/10.1007/s10067-016-3480-x CrossRefPubMed

18.

Vitale A, Emmi G, Lopalco G et al (2017) Long-term efficacy and safety of golimumab in the treatment of multirefractory Behçet’s disease. Clin Rheumatol 36:2063–2069. https://doi.org/10.1007/s10067-017-3627-4 CrossRefPubMed

19.

Vitale A, Rigante D, Lopalco G et al (2016) New therapeutic solutions for Behçet’s syndrome. Expert Opin Investig Drugs 25:827–840. https://doi.org/10.1080/13543784.2016.1181751 CrossRefPubMed

20.

Nguyen QD, Merrill PT, Jaffe GJ et al (2016) Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 388:1183–1192. https://doi.org/10.1016/S0140-6736(16)31339-3 CrossRefPubMed

21.

Jaffe GJ, Dick AD, Brézin AP et al (2016) Adalimumab in patients with active noninfectious uveitis. N Engl J Med 375:932–943. https://doi.org/10.1056/NEJMoa1509852 CrossRefPubMed

22.

Zeydan B, Uygunoglu U, Saip S et al (2016) Infliximab is a plausible alternative for neurologic complications of Behçet disease. Neurol Neuroimmunol neuroinflammation 3:e258. https://doi.org/10.1212/NXI.0000000000000258 CrossRef

23.

Fabiani C, Sota J, Vitale A et al (2017) Ten-Year Retention rate of infliximab in patients with Behçet’s disease-related uveitis. Ocul Immunol Inflamm 1–6. https://doi.org/10.1080/09273948.2017.1391297 CrossRefPubMed

24.

Emmi G, Silvestri E, Squatrito D et al (2016) Tocilizumab-induced exacerbation of mucosal ulcers in a patient with multi-refractory Behçet׳s disease. Semin Arthritis Rheum 46:e1–e2. https://doi.org/10.1016/j.semarthrit.2016.03.006 CrossRefPubMed

25.

Addimanda O, Pipitone N, Pazzola G, Salvarani C (2015) Tocilizumab for severe refractory neuro-Behçet: three cases IL-6 blockade in neuro-Behçet. Semin Arthritis Rheum 44:472–475. https://doi.org/10.1016/j.semarthrit.2014.08.004 CrossRefPubMed

26.

Mirouse A, Barete S, Monfort JB et al (2017) Ustekinumab for Behçet’s disease. J Autoimmun. https://doi.org/10.1016/j.jaut.2017.05.002 CrossRefPubMed

27.

Di Scala G, Bettiol A, Cojan RD et al (2018) Efficacy of the anti-IL 17 secukinumab in refractory Behçet’s syndrome: a preliminary study. J Autoimmun. https://doi.org/10.1016/j.jaut.2018.09.002 CrossRefPubMed

28.

YIlmaz I, Türk M, Nazik Bahçecioğlu S (2018) Successful rapid subcutaneous desensitization to anakinra in a case with a severe immediate-type hypersensitivity reaction. Eur Ann Allergy Clin Immunol 50:94–96. https://doi.org/10.23822/EurAnnACI.1764-1489.30 CrossRefPubMed

29.

Emmi G, Urban ML, Imazio M et al (2018) Use of interleukin-1 blockers in pericardial and cardiovascular diseases. Curr Cardiol Rep 20:61. https://doi.org/10.1007/s11886-018-1007-6 CrossRefPubMed

30.

Brucato A, Emmi G, Cantarini L et al (2018) Management of idiopathic recurrent pericarditis in adults and in children: a role for IL-1 receptor antagonism. Intern Emerg Med 13:475–489. https://doi.org/10.1007/s11739-018-1842-x CrossRefPubMed

31.

Colafrancesco S, Priori R, Valesini G et al (2017) Response to interleukin-1 inhibitors in 140 Italian patients with adult-onset still’s disease: a multicentre retrospective observational study. Front Pharmacol 8:369. https://doi.org/10.3389/fphar.2017.00369 CrossRefPubMedPubMedCentral

32.

Cavalli G, Dinarello CA (2018) Anakinra therapy for non-cancer inflammatory diseases. Front Pharmacol 9:1157. https://doi.org/10.3389/fphar.2018.01157 CrossRefPubMedPubMedCentral

33.

Astrakhantseva IV, Efimov GA, Drutskaya MS et al (2014) Modern anti-cytokine therapy of autoimmune diseases. Biochemistry 79:1308–1321. https://doi.org/10.1134/S0006297914120049 CrossRefPubMed

34.

Owyang AM, Issafras H, Corbin J et al XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1β-mediated diseases. MAbs 3:49–60

35.

Higgins JPT, Altman DG, Gotzsche PC et al (2011) The cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. https://doi.org/10.1136/bmj.d5928 CrossRefPubMedPubMedCentral

36.

Wells GA, Shea B, O’Connell D et al (2013) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Hosp Res Inst doi. https://doi.org/10.2307/632432 CrossRef

37.

Fabiani C, Vitale A, Rigante D et al (2018) The presence of uveitis is associated with a sustained response to the interleukin (IL)-1 inhibitors anakinra and canakinumab in Behçet’s disease. Ocul Immunol Inflamm 1–7. https://doi.org/10.1080/09273948.2018.1511810

38.

Sota J, Vitale A, Insalaco A et al (2018) Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study. Clin Rheumatol. https://doi.org/10.1007/s10067-018-4119-x CrossRefPubMed

39.

Pagnini I, Bondi T, Simonini G et al (2015) Successful treatment with canakinumab of a paediatric patient with resistant Behçet’s disease. Rheumatology (Oxford) 54:1327–1328. https://doi.org/10.1093/rheumatology/kev197 CrossRef

40.

Emmi G, Silvestri E, Ciucciarelli L et al (2014) Reply: anti-IL1 blocking agents in drug-resistant Behçet’s syndrome: our little case series. Clin Exp Rheumatol 32:S172PubMed

41.

Caso F, Rigante D, Vitale A et al (2014) Efficacy of anakinra in refractory Behçet’s disease sacroiliitis. Clin Exp Rheumatol 32:S171PubMed

42.

Vitale A, Rigante D, Caso F et al (2014) Inhibition of interleukin-1 by canakinumab as a successful mono-drug strategy for the treatment of refractory behçet’s disease: a case series. Dermatology 228:211–214. https://doi.org/10.1159/000358125 CrossRefPubMed

43.

Cantarini L, Vitale A, Scalini P et al (2015) Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol 34:1293–1301. https://doi.org/10.1007/s10067-013-2443-8 CrossRefPubMed

44.

Emmi G, Silvestri E, Cameli A et al (2013) Anakinra for resistant Behçet uveitis: why not? Clin Exp Rheumatol 31:152–153PubMed

45.

Cantarini L, Vitale A, Borri M et al (2012) Successful use of canakinumab in a patient with resistant Behçet’s disease. Clin Exp Rheumatol 30:S115PubMed

46.

Ugurlu S, Ucar D, Seyahi E et al (2012) Canakinumab in a patient with juvenile Behçet’s syndrome with refractory eye disease. Ann Rheum Dis 71:1591–1592. https://doi.org/10.1136/annrheumdis-2012-201383 CrossRef

47.

Bilginer Y, Ayaz NA, Ozen S (2010) Anti-IL-1 treatment for secondary amyloidosis in an adolescent with FMF and Behçet’s disease. Clin Rheumatol 29:209–210. https://doi.org/10.1007/s10067-009-1279-8 CrossRefPubMed

48.

Botsios C, Sfriso P, Furlan A et al (2008) Resistant Behçet disease responsive to anakinra. Ann Intern Med 149:284–286CrossRefPubMed

49.

Orlando I, Vitale A, Rigante D et al (2017) Long-term efficacy and safety of the interleukin-1 inhibitors anakinra and canakinumab in refractory Behçet disease uveitis and concomitant bladder papillary carcinoma. Intern Med J 47:1086–1088. https://doi.org/10.1111/imj.13538 CrossRefPubMed

50.

Tugal-Tutkun I, Pavesio C, De Cordoue A et al (2018) Use of gevokizumab in patients with Behçet’s disease uveitis: an international, randomized, double-masked, placebo-controlled study and open-label extension study. Ocul Immunol Inflamm 26:1023–1033. https://doi.org/10.1080/09273948.2017.1421233 CrossRefPubMed

51.

Tugal-Tutkun I, Kadayifcilar S, Khairallah M et al (2017) Safety and efficacy of gevokizumab in patients with Behçet’s disease uveitis: results of an exploratory phase 2 study. Ocul Immunol Inflamm 25:62–70. https://doi.org/10.3109/09273948.2015.1092558 CrossRef

52.

Vitale A, Rigante D, Caso F et al (2017) Interleukin-1 blockade in neuro-Behçet’s disease: a case-based reflection. Int J Rheum Dis 20:1046–1049. https://doi.org/10.1111/1756-185X.12680 CrossRefPubMed

53.

Gül A, Tugal-Tutkun I, Dinarello CA et al (2012) Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behcet’s disease: an open-label pilot study. Ann Rheum Dis 71:563–566. https://doi.org/10.1136/annrheumdis-2011-155143 CrossRefPubMed

54.

Grayson PC, Yazici Y, Merideth M et al (2017) Treatment of mucocutaneous manifestations in Behçet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther. https://doi.org/10.1186/s13075-017-1222-3 CrossRefPubMedPubMedCentral

55.

Fabiani C, Vitale A, Emmi G et al (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol. https://doi.org/10.1007/s10067-016-3506-4 CrossRefPubMed

56.

Vitale A, Insalaco A, Sfriso P et al (2016) A snapshot on the on-label and off-label use of the interleukin-1 inhibitors in Italy among rheumatologists and pediatric rheumatologists: a nationwide multi-center retrospective observational study. Front Pharmacol. https://doi.org/10.3389/fphar.2016.00380 CrossRefPubMedPubMedCentral

57.

Emmi G, Silvestri E, Cantarini L et al (2017) Rapid desensitization to anakinra-related delayed reaction: need for a standardized protocol. J Dermatol 44:981–982. https://doi.org/10.1111/1346-8138.13619 CrossRefPubMed

58.

Emmi G, Silvestri E, Squatrito D et al (2017) Long-term efficacy and safety of anakinra in a patient with Behçet’s disease and concomitant tuberculosis infection. Int J Dermatol 56:218–220. https://doi.org/10.1111/ijd.13337 CrossRefPubMed

59.

Cantarini L, Talarico R, Generali E et al (2015) Safety profile of biologic agents for Behçet’s disease in a multicenter observational cohort study. Int J Rheum Dis 1–6. https://doi.org/10.1111/1756-185X.12732 CrossRefPubMed

60.

Emmi G, Talarico R, Lopalco G et al (2016) Efficacy and safety profile of anti-interleukin-1 treatment in Behçet’s disease: a multicenter retrospective study. Clin Rheumatol 35:1281–1286. https://doi.org/10.1007/s10067-015-3004-0 CrossRefPubMed

61.

International Study Group for Behet’s Disease (1990) Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet. https://doi.org/10.1016/0140-6736(90)92643-V CrossRef

62.

Kaneko F, Togashi A, Nomura E, Nakamura K (2014) A new diagnostic way for Behcet’s disease: skin prick with self-saliva. Genet Res Int. https://doi.org/10.1155/2014/581468 CrossRefPubMedPubMedCentral

63.

Greco A, De Virgilio A, Ralli M et al (2018) Behçet’s disease: new insights into pathophysiology, clinical features and treatment options. Autoimmun Rev. https://doi.org/10.1016/j.autrev.2017.12.006 CrossRefPubMed

64.

Yazici H, Ugurlu S, Seyahi E (2012) Behçet syndrome: is it one condition? Clin Rev Allergy Immunol 43:275–280. https://doi.org/10.1007/s12016-012-8319-x CrossRefPubMed

65.

Ma D, Zhang C, Wang R et al (2014) Etanercept in the treatment of intestinal Behcet’s disease. Cell Biochem Biophys 69:735–739. https://doi.org/10.1007/s12013-014-9860-4 CrossRefPubMed

66.

Fabiani C, Sota J, Rigante D et al (2018) Efficacy of adalimumab and infliximab in recalcitrant retinal vasculitis inadequately responsive to other immunomodulatory therapies. Clin Rheumatol. https://doi.org/10.1007/s10067-018-4133-z CrossRefPubMed

67.

Deroux A, Chiquet C, Bouillet L (2015) Tocilizumab in severe and refractory Behcet’s disease: four cases and literature review. Semin Arthritis Rheum doi. https://doi.org/10.1016/j.semarthrit.2015.11.012 CrossRef

Titel: The right place of interleukin-1 inhibitors in the treatment of Behçet’s syndrome: a systematic review
verfasst von: Alessandra Bettiol
Elena Silvestri
Gerardo Di Scala
Amedeo Amedei
Matteo Becatti
Claudia Fiorillo
Giuseppe Lopalco
Carlo Salvarani
Luca Cantarini
Alessandra Soriano
Giacomo Emmi
Publikationsdatum: 25.02.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 6/2019
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-019-04259-y

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