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Abstract

doubleblind, placebocontrolled, randomised PSUMMIT 2 trial. Ann Rheum Dis 2014;73:990– 9. 4. Conway R, O’Neill L, Gallagher P, McCarthy GM, Murphy CC, Veale DJ, et al. Ustekinumab for refractory giant cell arteritis: a prospective 52week trial. Semin Arthritis Rheum 2018;48:523– 8. 5. Conway R, O’Neill L, O’Flynn E, Gallagher P, McCarthy GM, Murphy CC, et al. Ustekinumab for the treatment of refractory giant cell arteritis. Ann Rheum Dis 2016;75:1578– 9. 6. Samson M, Ghesquière T, Berthier S, Bonnotte B. Ustekinumab inhibits Th1 and Th17 polarisation in a patient with giant cell arteritis. Ann Rheum Dis 2018;77:e6. 7. Samson M, CorberaBellalta M, Audia S, PlanasRigol E, Martin L, Cid MC, et al. Recent advances in our understanding of giant cell arteritis pathogenesis. Autoimmun Rev 2017;16:833– 44. 8. Deng J, Younge BR, Olshen RA, Goronzy JJ, Weyand CM. Th17 and Th1 Tcell responses in giant cell arteritis. Circulation 2010;121:906– 15. 9. Samson M, EspígolFrigolé G, TerradesGarcía N, PrietoGonzález S, CorberaBellalta M, AlbaRovira R, et al. Biological treatments in giant cell arteritis & Takayasu arteritis. Eur J Intern Med 2018;50:12– 19. 10. McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, doubleblind, placebocontrolled PSUMMIT 1 trial. Lancet 2013;382:780– 9. 11. Gordon KB, Papp KA, Langley RG, Ho V, Kimball AB, Guzzo C, et al. Longterm safety experience of ustekinumab in patients with moderate to severe psoriasis (Part II of II): results from analyses of infections and malignancy from pooled phase II and III clinical trials. J Am Acad Dermatol 2012;66:742– 51. Although this study suggests that, unlike TCZ (2), UST is ineffective in controlling GCA unless it is associated with glucocorticoids, we have several reasons to believe it is too early to draw conclusions regarding the use of UST as a glucocorticoidsparing drug in GCA. First, this trial was not controlled, and more importantly, the prednisone regimen used in this study was short. Unlike TCZ and other biologics that directly target proinflammatory cytokines, resulting in rapid resolution of inflammation, UST modulates T cell homeostasis by targeting both interleukin-12 (IL-12) and IL23 pathways through a blockade of the p40 subunit, resulting in an onset of action 8 to 12 weeks later (3). In the study by Matza et al (1), patients were receiving 12.5, 10, or 6 mg/day of prednisone at 12 weeks (depending on their starting dose: 60 mg [3 patients], 40 mg [9 patients] or 20 mg [1 patient]). We therefore assume that many patients relapsed because the prednisone dose was too low to control GCA when UST became effective, which may explain why the authors did not observe the effectiveness of UST as in previous reports (4– 6). Recent advances in our understanding of the pathophysiology of GCA have shown the critical implication of Th1 and Th17 cells, which produce interferonγ (IFN γ) and IL17, respectively (7). Unlike Th17 cells, Th1 cells are resistant to glucocorticoids (8); this resistance results in the chronic production of IFN γ in GCA, which plays a major role in triggering vascular remodeling and for which there is currently no effective treatment (9). By blocking IL12 and IL23, the 2 key cytokines involved in Th1 and Th17 polarization, UST provides a great opportunity to disrupt both Th1 and Th17 pathways (6), potentially leading to better control of vascular remodeling and inflammation in GCA. In addition, UST has shown an excellent safety profile in clinical trials (10,11), which is a considerable advantage for patients experiencing relapsing GCA, who are often elderly and frail with a high risk of infection. For all these reasons, we believe that UST remains an interesting treatment that should particularly be evaluated for patients with relapsing GCA, especially if they are not eligible for TCZ. No potential conflicts of interest relevant to this letter were reported.