Cytokine storm after cessation of tocilizumab in a patient with refractory Takayasu arteritis

Abstract

Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis of unknown pathogenesis mainly affecting aorta and its major branches [ [1] Isobe M. Takayasu arteritis revisited: current diagnosis and treatment. Int. J. Cardiol. 2013; 168: 3-10 Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar ]. Glucocorticoids (GCs) are the principal therapy for the treatment of TAK [ [2] Mukhtyar C. Guillevin L. Cid M.C. et al. EULAR recommendations for the management of large vessel vasculitis. Ann. Rheum. Dis. 2009; 68: 318-323 Crossref PubMed Scopus (482) Google Scholar ]. Although GCs suppress the clinical symptoms and signs of inflammation when administered in moderate to high doses, a sizable number of patients relapse upon tapering of the GC dose or discontinuation [ [3] Maksimowicz-McKinnon K. Clark T.M. Hoffman G.S. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007; 56: 1000-1009 Crossref PubMed Scopus (372) Google Scholar ]. Recent studies have shown that interleukin-6 (IL-6) blockade with the anti-human IL-6 receptor (IL-6R) humanized monoclonal antibody, tocilizumab (TCZ), might be effective for treating the refractory patients with TAK [ 4 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: 1197-1200 Crossref PubMed Scopus (170) Google Scholar , 5 Salvarani C. Magnani L. Catanoso M. et al. Tocilizumab: a novel therapy for patients with large-vessel vasculitis. Rheumatology. 2012; 51: 151-156 Crossref PubMed Scopus (188) Google Scholar , 6 Seitz M. Reichenbach S. Bonel H.M. Adler S. Wermelinger F. Villiger P.M. Rapid induction of remission in large vessel vasculitis by IL-6 blockade. Swiss Med. Wkly. 2011; 141 PubMed Google Scholar , 7 Unizony S. Arias-Urdaneta L. Miloslavsky E. Arvikar S. Khosroshahi A. Keroack B. Stone J.R. Stone J.H. Tocilizumab for the treatmen of large-vessel vasculitis (giant cell areritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res. (Hoboken). 2012; 64: 1720-1729 Crossref PubMed Scopus (236) Google Scholar , 8 Nakaoka Y. Higuchi K. Arita Y. et al. Tocilizumab for the treatment of patients with refractory Takayasu arteritis. Int. Heart J. 2013; 54: 405-411 Crossref PubMed Scopus (56) Google Scholar ]. Since continuous therapy with TCZ strains medical finances due to its expensive cost, we need to develop safe methods for terminating TCZ therapy after induction of remission. In addition, it is unclear whether discontinuation of TCZ might cause a disease flare-up in a TAK patient in remission. Here, we present a TAK patient who showed a recurrence of TAK after cessation of TCZ with elevation of various inflammatory cytokines, so-called “cytokine storm”. Retreatment with TCZ and a subsequent administration of methotrexate (MTX) along with of the dosage increment in GCs were successful for maintaining remission.