EXPERIENCE WITH TOCILIZUMAB, AN INTERLEUKIN 6 INHIBITOR, USED FOR THE TREATMENT OF GIANT CELL ARTERITIS WITH SEVERE COMORBIDITY

Abstract

Giant cell arteritis (GCA), formerly known as Horton's disease, is among the most common diseases from a group of systemic vasculitides; its clinical significance is complemented with the potential involvement of the coronary arteries, aorta, and cranial arteries with development of ischemic optic neuropathy if there is no timely treatment that results in rapid and irreversible visual loss. The elderly age of patients is one of the key aspects of GCA. Therefore, the disease is often accompanied by various comorbidities that have considerable impact on the choice of a treatment regimen and limit the use of standard therapy with glucocorticoids (GCs). The complications due to GC treatment can be competitive in severity with GCA, especially in elderly multimorbid patients. Progress in rheumatology due to the introduction of biological agents (BAs) has created the preconditions for the development of a new area of pharmacotherapy for GCA associated with interleukin 6 (IL6) inhibition using tocilizumab (TCZ). According to the results of two randomized placebocontrolled trials (RPCTs), which were published in 2016, the rate of remission with TCZ treatment was significantly higher in patients with GCA than that in the placebo group (p = 0.03–0.0001), as is relapse-free survival after 52 weeks of TCZ treatment (85 and 20%, respectively; p ≤ 0.001), the incidence of serious adverse events (AE) was 14–35%. In 2017, the results of Phase III GiACTA RPCT became the basis for approval of the use of TCZ for the treatment of GCA in the United States and Europe. The authors present their own results of a small prospective study of TCZ in 7 patients with active GCA with severe comorbidity, including multimorbidity, that potentially increases the risk for AE due to GC therapy. The mean age of the patients was 71.3±7.6 years; among them there was one man and 6 women. The administration of TCZ in a monthly dose of 2.3–8.8 mg/kg for 1–10 months with a cumulative dose of 10–58.1 mg/kg could reduce the mean daily dose of prednisolone to 15 (5–32.5) mg, thereby preventing the development or progression of AE, and all the 7 patients could rather rapidly achieve GCA remission. A recurrence after therapy discontinuation was noted in one patient. TCZ treatment was accompanied by serious AE (purulent elbow bursitis); and other two patients had AE a few months after TCZ discontinuation. There were no fatal outcomes. Thus, the presented results suggest that the use of IL6 inhibitors in patients with GCA, including those with severe comorbidity, can be regarded as a potentially effective innovative (off-label) treatment strategy with an acceptable safety profile. The further expansion of an evidence base and the clarification of the medical and economic aspects of TCZ treatment in some groups of GCA will help justify the choice of BAs.