INNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATURE
https://doi.org/10.14412/1995-4484-2017-536-548
Abstract
The need for further improvement of treatments for Takayasu’s arteritis (TA), the progress in understanding the mechanisms of the disease, and the introduction of biological agents (BA) in rheumatology practice have created preconditions for developing a new TA pharmacotherapy using BA associated with interleukin 6 (IL-6) inhibition. The authors describe their two own cases of tocilizumab (TCZ) use for complicated TA. They analyze the results of TCZ treatment by the data of preliminary trials in 115 patients with TA, which have been published in 30 literature sources, as well as the results of Phase III double-blind, randomized placebo-controlled trials (RPCTs) of the safety and efficacy of TCZ in 18 patients with refractory TA. In one case with a long history of complicated TA, the control of TA activity and the reduction in the dose of glucocorticoids due to TCZ use contributed to the favorable course of pregnancy and labor. In the other case with the onset of TA and focal pulmonary tuberculosis (TB) treated with anti-TB drugs during TCZ monotherapy for 6 months could control TA and achieve TB cure. Preliminary trials showed that TCZ treatment-induced remission or improvement was observed in 85% of patients with TA, including that with a refractory course. RPCTs indicated that the relapse-free survival after 6-month maintenance treatment with TCZ was higher than that in the placebo group (51 and 23%, respectively); but the differences failed to reach statistical significance (p = 0.0596). Due to the fact that a recurrence of TA can occur in patients treated with TCZ, it is appropriate to combine this drug with cytostatic drugs, methotrexate in particular. The use of IL-6 inhibitors should be considered as a potentially effective and relatively safe innovative (off-label) treatment for refractory TA in patients with intolerance or contraindications to standard therapy, which requires further larger randomized clinical trials. Since now there is no universal imaging method that could provide comprehensive information on the status of vessels in TA; the standardization of future clinical trials of BAs requires the improvement of methods for evaluating the efficiency of treatment for TA; moreover, monitoring of disease activity should include a comprehensive assessment of clinical data, current laboratory biomarkers, and instrumental imaging techniques, primarily non-invasive ones.
About the Authors
T. V. BeketovaRussian Federation
34A, Kashirskoe Shosse, Moscow 115522
E. L. Nasonov
Russian Federation
34A, Kashirskoe Shosse, Moscow 115522
Department of Rheumatology, Institute of Professional Education
8, Trubetskaya St., Build. 2, Moscow 119991
References
1. Jennette J, Falk R, Bacon P, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11. doi: 10.1002/art.37715
2. Carmona FD, Coit P, Saruhan-Direskeneli G, et al; Spanish GCA Study Group; Italian GCA Study Group; Turkish Takayasu Study Group; Vasculitis Clinical Research Consortium. Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy. Sci Rep. 2017;7:439-53. doi: 10.1038/srep43953
3. Saruhan-Direskeneli G, Hughes T, Aksu K, et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013;93:298-305. doi: 10.1016/j.ajhg.2013.05.026
4. Carmona FD, Mackie SL, Martin JE, et al. A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility. Am J Hum Genet. 2015;96:565-80. doi: 10.1016/j.ajhg.2015.02.009
5. Kitamura H, Kobayashi Y, Kimura A, Numano F. Association of clinical manifestations with HLA-B alleles in Takayasu arteritis. Int J Cardiol. 1998;66 Suppl 1:121-6. doi: 10.1016/S0167-5273(98)00159-4
6. Ohigashi H, Tamura N, Ebana Y, et al. Effects of immunosuppressive and biological agents on refractory Takayasu arteritis patients unresponsive to glucocorticoid treatment. J Cardiol. 2017;69(5):774-8. doi: 10.1016/j.jjcc.2016.07.009
7. Moriwaki R, Noda M, Yajima M, et al. Clinical manifestations of Takayasu arteritis in India and Japan – new classification of angiographic findings. Angiology. 1997;48(5):369-79. doi: 10.1177/000331979704800501
8. Direskeneli H, Aydin SZ, Merkel PA. Assessment of disease activity and progression in Takayasu’s arteritis. Clin Exp Rheumatol. 2011;29 Suppl 64:86-91.
9. Alibaz-Oner F, Direskeneli H. Update on Takayasu’s arteritis. Presse Med. 2015;44:259-65. doi: 10.1016/j.lpm.2015.01.015
10. Freitas D, Camargo C, Mariz H, et al. Takayasu arteritis: assessment of response to medical therapy based on clinical activity criteria and imaging techniques. Rheumatol Int. 2012;32:703-9. doi: 10.1007/s00296-010-1694-9
11. Fukui S, Ichinose K, Tsuji S, et al. Hypocholesterolemia predicts relapses in patients with Takayasu arteritis. Mod Rheumatol. 2016;26(3):415-20. doi: 10.3109/14397595.2015.1083148
12. Hong S, Bae S, Ahn S, et al. Outcome of Takayasu arteritis with inactive disease at diagnosis: the extent of vascular involvement as a predictor of activation. J Rheumatol. 2015;42(3):489-94. doi: 10.3899/jrheum.140981
13. Maksimowicz-McKinnon K, Clark T, Hoffman G. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007;56(3):1000-9. doi: 10.1002/art.22404
14. Isobe M. Takayasu arteritis revisited: current diagnosis and treatment. Int J Cardiol. 2013;168:3-10. doi: 10.1016/j.ijcard.2013.01.022
15. Seko Y, Sato O, Takagi A, et al. Restricted usage of T-cell receptor Vα-Vβ genes in infiltrating cells in aortic tissue of patients with Takayasu's arteritis. Circulation. 1996;93(10):1788-90. doi: 10.1161/01.CIR.93.10.1788
16. Kong X, Sun Y, Ma L, et al. The critical role of IL-6 in the pathogenesis of Takayasu arteritis. Clin Exp Rheumatol. 2016;34(3 Suppl 97):21-7.
17. Salvarani C, Cantini F, Boiardi L, Hunder G. Laboratory investigations useful in giant cell arteritis and Takayasu's arteritis. Clin Exp Rheumatol. 2003;21(6 Suppl 32):23-8.
18. Noris M, Daina E, Gamba S, et al. Interleukin-6 and RANTES in Takayasu arteritis: a guide for therapeutic decisions? Circulation. 1999;100(1):55-60. doi: 10.1161/01.CIR.100.1.55
19. Park M, Lee S, Park Y, Lee S. Serum cytokine profiles and their correlations with disease activity in Takayasu's arteritis. Rheumatology. 2006;45(5):545-8. doi: 10.1093/rheumatology/kei266
20. Alibaz-Oner F, Yentü r SP, Saruhan-Direskeneli G, Direskeneli H. Serum cytokine profiles in Takayasu's arteritis: search for biomarkers. Clin Exp Rheumatol. 2015;33(2 Suppl 89):32-5.
21. Pulsatelli L, Boiardi L, Assirelli E, et al. Interleukin-6 and soluble interleukin-6 receptor are elevated in large-vessel vasculitis: a cross-sectional and longitudinal study. Clin Exp Rheumatol. 2017;35 Suppl 103(1):102-10.
22. Nishimoto N, Nakahara H, Yoshio-Hoshino N, Mima T. Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody. Arthritis Rheum. 2008;58:1197-200. doi: 10.1002/art.23373
23. Nakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: Results from a randomized, double-blind, placebo-controlled, phase 3 trial in Japan [abstract]. Arthritis Rheum. 2016;68 Suppl 10. Available from: http://acrabstracts.org/abstract/efficacy-and-safety-of-tocilizumab-in-patients-with- refractory-takayasu-arteritisresults-from-a-randomized-double-blind-placebo- controlledphase-3-trial-in-japan/. Accessed August 2, 2017.
24. Seitz M, Reichenbach S, Bonel H, et al. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. A case series. Swiss Medical Weekly. 2011;141:w13156.
25. Bravo Mancheno B, Perin F, del Mar Rodriguez Vazquez del Rey M, et al. Successful tocilizumab treatment in a child with refractory Takayasu arteritis. Pediatrics. 2012;130:1720-4. doi: 10.1542/peds.2012-1384
26. De Kruif M, van Gorp E, Bel E, et al. Streptococcal lung abscesses from a dental focus following tocilizumab: a case report. Clin Exp Rheumatol. 2012;30:951-3.
27. Unizony S, Arias-Urdaneta L, Miloslavsky E, et al. Tocilizumab for the treatment of large- vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012;64(11):1720-9. doi: 10.1002/acr.21750
28. Salvarani C, Magnani L, Catanoso M, et al. Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology (Oxford). 2012;51:151-6. doi: 10.1093/rheumatology/ker296
29. Salvarani C, Magnani L, Catanoso M, et al. Rescue treatment with tocilizumab for takayasu arteritis resistant to TNF-α blockers. Clin Exp Rheumatol. 2012;30(70):90-3.
30. Bredemeier M, Rocha CM, Barbosa MV, Pitrez EH. One-year clinical and radiological evolution of a patient with refractory Takayasu's arteritis under treatment with tocilizumab. Clin Exp Rheumatol. 2012;30:98-100.
31. Abisror N, Mekinian A, Lavigne C, et al. Et club rhumatismes et inflammation, and SNFMI. Tocilizumab in refractory Takayasu arteritis: a case series and updated literature review. Autoimmun Rev. 2013;12(12):1143-9. doi: 10.1016/j.autrev.2013.06.019
32. Goel R, Danda D, Kumar S, Joseph G. Rapid control of disease activity by tocilizumab in 10 «difficult-to-treat» cases of Takayasu arteritis. Int J Rheum Dis. 2013;16:754-61. doi: 10.1111/1756-185X.12220
33. Xenitidis T, Horger M, Zeh G, et al. Sustained inflammation of the aortic wall despite tocilizumab treatment in two cases of Takayasu arteritis. Rheumatology (Oxford). 2013;52(9):1729-31. doi: 10.1093/rheumatology/ket107
34. Nakaoka Y, Higuchi K, Arita Y, et al. Tocilizumab for the treatment of patients with refractory Takayasu arteritis. Int Heart J. 2013;54:405-11. doi: 10.1536/ihj.54.405
35. Tombetti E, Franchini S, Papa M, et al. Treatment of refractory Takayasu arteritis with tocilizumab: 7 Italian patients from a single referral center. J Rheumatol. 2013;40(12):2047- 51. doi: 10.3899/jrheum.130536
36. Canas C, Canas F, Izquierdo J, et al. Efficacy and safety of antiinterleukin 6 receptor monoclonal antibody tocilizumab) in Colombian patients with Takayasu arteritis. J Clin Rheumatol. 2014;20(3):125-9. doi: 10.1097/RHU.0000000000000098
37. Loricera J, Blanco R, Castaneda S, et al. Tocilizumab in refractory aortitis: study on 16 patients and literature review. Clin Exp Rheumatol. 2014;32 Suppl. 82:79-89. doi: 10.1136/annrheumdis-2014-eular.2984
38. Youngstein T, Peters J, Hamdulay S, et al. Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-alpha and IL-6 receptor targeted therapies in refractory Takayasu arteritis. Clin Exp Rheumatol. 2014;32(3 Suppl. 82):11-8.
39. Schiavon F, Cuffaro S, Ometto F, et al. Takayasu arteritis and NYHA III/IV idiopathic cardiomiopathy: tocilizumab proves effective and safe. Joint Bone Spine. 2014;81:278-9. doi: 10.1016/j.jbspin.2013.11.008
40. Mekinian A, Comarmond C, Resche-Rigon M, et al. Efficacy of biological-targeted treatments in Takayasu arteritis: multicenter, retrospective study of 49 patients. Circulation. 2015;132(18):1693- 700. doi: 10.1161/CIRCULATIONAHA.114.014321
41. Osman M, Emery D, Yacyshyn E. Tocilizumab for treating Takayasu’s arteritis and associated stroke: a case series and updated review of the literature. J Stroke Cerebrovasc Dis. 2015;24:1291-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.01.032
42. Arita Y, Nakaoka Y, Otsuki M, et al. Cytokine storm after cessation of tocilizumab in a patient with refractory Takayasu arteritis. Int J Cardiol. 2015;187:319-21. doi: 10.1016/j.ijcard.2015.03.399
43. Novikov P, Smitienko I, Elonakov A, et al. THU0293 safety and efficacy of short-term treatment with tocilizumab in patients with refractory Takayasu arteritis. Ann Rheum Dis. 2015;74:302. doi: 10.1136/annrheumdis-2015-eular.6048
44. Kostina Y, Lyskina G. FRI0282 experience of biological agents treatment of refractory takayasu arteritis in children. Ann Rheum Dis. 2015;74:527. doi: 10.1136/annrheumdis-2015- eular.3411
45. Martin Guillen S, Alvarez de Cienfuegos A, Hurtado Garcia R. New drugs in Takayasu arteritis, role of tocilizumab. Reumatol Clin. 2016;12(6):358-9. doi: 10.1016/j.reuma.2016.01.008
46. Ahmed M, Mansoor S, Assad S, et al. Refractory case of Takayasu arteritis in a young woman: A clinical challenge. Cureus. 2016;8(11):872. doi: 10.7759/cureus.872
47. Spira D, Xenitidis T, Henes J, Horger M. MRI parametric monitoring of biological therapies in primary large vessel vasculitides: A pilot study. Br J Radiol. 2016;89(1058):20150892. doi: 10.1259/bjr.20150892
48. Vinicki J, Garcia-Vicuna R, Arredondo M, et al. Sustained remission after long-term biological therapy in patients with large vessel vasculitis: an analysis of ten cases. Reumatol Clin. 2017;13(4):210-3. doi: 10.1016/j.reuma.2016.06.003
49. Iwagaitsu S, Naniwa T. Improvement of arterial wall lesions in parallel with decrease of plasma pentraxin-3 levels in a patient with refractory Takayasu arteritis after treatment with tocilizumab. Case Rep Rheumatol. 2017;2017:4580967. doi: 10.1155/2017/4580967
50. Zhou J, Chen Z, Li J, et al. The efficacy of tocilizumab for the treatment of Chinese Takayasu's arteritis. Clin Exp Rheumatol. 2017;35 Suppl 103(1):171-5.
51. Batu ED, Sö nmez HE, Hazirolan T, et al. Tocilizumab treatment in childhood Takayasu arteritis: Case series of four patients and systematic review of the literature. Semin Arthritis Rheum. 2017;46(4):529-35. doi: 10.1016/j.semarthrit.2016.07.012
52. Hoffman GS, Leavitt RY, Kerr GS, et al. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum. 1994;37:578-82. doi: 10.1002/art.1780370420
53. Comarmond C, Mirault T, Biard L, et al; French Takayasu Network. Takayasu arteritis and pregnancy. Arthritis Rheum. 2015;67(12):3262-9. doi: 10.1002/art.39335
54. Hoeltzenbein M, Beck E, Rajwanshi R, et al. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum. 2016;46(2):238-45. doi: 10.1016/j.semarthrit.2016.05.004
55. Покровский АВ, Зотиков АЕ, Юдин ВИ. Неспецифический аортоартериит (болезнь Такаясу). Москва: ИРСИСЪ; 2002 [Pokrovskii AV, Zotikov AE, Yudin VI. Nespetsificheskii aortoarteriit (bolezn' Takayasu) [Nonspecific aortoarteritis (Takayasu's disease)]. Moscow: IRSIS; 2002].
56. Mavrogeni S, Dimitroulas T, Chatziioannou SN, et al. The role of multimodality imaging in the evaluation of Takayasu arteritis. Semin Arthritis Rheum. 2013;42:401-12. doi: 10.1016/j.semarthrit.2012.07.005
57. Schmidt WA. Imaging in vasculitis. Best Pract Res Clin Rheumatol. 2013;27:107-18. doi: 10.1016/j.berh.2013.01.001
58. Muratore F, Pipitone N, Salvarani C, Schmidt WA. Imaging of vasculitis: State of the art. Best Pract Res Clin Rheumatol. 2016;30(4):688-706. doi: 10.1016/j.berh.2016.09.010
59. Germano G, Monti S, Ponte C, et al. The role of ultrasound in the diagnosis and follow-up of large-vessel vasculitis: an update. Clin Exp Rheumatol. 2017;35 Suppl 103(1):194-8.
60. Bucci M, Aparici CM, Hawkins R, et al. Validation of FDG uptake in the arterial wall as an imaging biomarker of atherosclerotic plaques with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). J Neuroimaging. 2014;24(2):117-23. doi: 10.1111/j.1552-6569.2012.00740.x
61. Kerr G, Hallahan C, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994;120:919- 29. doi: 10.7326/0003-4819-120-11-199406010-00004
62. Matsuyama A, Sakai N, Ishigami M, et al. Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation. 2003;108:1469-73. doi: 10.1161/01.CIR.0000090689.69973.B1
63. Ishihara T, Haraguchi G, Tezuka D, et al. Diagnosis and assessment of Takayasu arteritis by multiple biomarkers. Circ J. 2013;77:477-83. doi: 10.1253/circj.CJ-12-0131
64. Bottazzi B, Doni A, Garlanda C, Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157-83. doi: 10.1146/annurev-immunol-030409-101305
65. Dagna L, Salvo F, Tiraboschi M, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med. 2011;155(7):425-33. doi: 10.7326/0003-4819-155-7- 201110040-00005
66. Tezuka D, Haraguchi G, Ishihara T, et al. High Standardized Uptake Value of 18F- Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography was correlated with Disease Activity in Patients with Takayasu Arteritis. Circulation. 2010;122:article A15229.
67. Hoffman GS, Merkel PA, Brasington RD, et al. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum. 2004;50:2296-304. doi: 10.1002/art.20300
68. Molloy E, Langford C, Clark T, et al. Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Ann Rheum Dis. 2008;67:1567-9. doi: 10.1136/ard.2008.093260
69. Comarmond C, Plaisier E, Dahan K, et al. Anti TNF-α in refractory Takayasu’s arteritis: cases series and review of the literature. Autoimmun Rev. 2012;11:678-84. doi: 10.1016/j.autrev.2011.11.025
70. Mekinian A, Neel A, Sibilia J, et al; Club Rhumatismes et Inflammation, French Vasculitis Study Group and Societe Nationale Francaise de Medecine Interne. Efficacy and tolerance of infliximab in refractory Takayasu arteritis: French multicentre study. Rheumatology (Oxford). 2012;51(5):882-6. doi: 10.1093/rheumatology/ker380
71. Schmidt J, Kermani TA, Bacani AK, et al. Tumor necrosis factor inhibitors in patients with Takayasu arteritis: experience from a referral center with longterm follow-up. Arthritis Care Res 2012;64:1079-83. doi: 10.1002/acr.21636
72. Tanaka Y, Martin Mola E. IL-6 targeting compared to TNF targeting in rheumatoid arthritis: studies of olokizumab, sarilumab and sirukumab. Ann Rheum Dis. 2014;73(9):1595- 7. doi: 10.1136/annrheumdis-2013-205002
73. Lim A, Lee G, Jang S, et al. Comparison of clinical characteristics in patients with Takayasu arteritis with and without concomitant tuberculosis. Heart Vessels. 2016;31(8):1277-84. doi: 10.1007/s00380-015-0731-8
74. Arnaud L, Cambau E, Brocheriou I, et al. Absence of Mycobacterium tuberculosis in arterial lesions from patients with Takayasu's arteritis. J Rheumatol. 2009;36(8):1682-5. doi: 10.3899/jrheum.080953
75. Carvalho E, de Souza A, Leao S, et al. Absence of mycobacterial DNA in peripheral blood and artery specimens in patients with Takayasu arteritis. Clin Rheumatol. 2017;36(1):205-8. doi: 10.1007/s10067-016-3400-0
Review
For citations:
Beketova T.V., Nasonov E.L. INNOVATIVE TREATMENTS FOR TAKAYASU’S ARTERITIS: A FOCUS ON INTERLEUKIN-6 INHIBITORS. THE AUTHORS’ EXPERIENCE WITH TOCILIZUMAB AND A REVIEW OF LITERATURE. Rheumatology Science and Practice. 2017;55(5):536-548. (In Russ.) https://doi.org/10.14412/1995-4484-2017-536-548