Current advances in the treatment of giant cell arteritis: the role of biologics

Abstract

Giant cell arteritis (GCA) is the most common form of systemic vasculitis. It is a potentially severe disease with 25% of patients suffering vision loss or stroke. Our treatment paradigm is based on glucocorticoids. Glucocorticoids are required in high doses for prolonged periods and subsequently are associated with a significant amount of treatment-related morbidity. Alternative treatment options are urgently needed to minimize these glucocorticoid adverse events. Many other agents, such as methotrexate and tumour necrosis factor alpha inhibitors have been used in GCA, with limited or no evidence of benefit. Our emerging understanding of the pathogenic processes involved in GCA has led to an increased interest in the use of biologic agents to treat the disease. Two randomized controlled trials have recently reported dramatic effects of the use of the interleukin-6 targeted biologic tocilizumab in GCA, with significant increases in remission rates and decreases in glucocorticoid burden. While encouraging, longer-term and additional outcomes are awaited to clarify the exact positioning of tocilizumab in the treatment approach. Emerging data for other biologic agents, particularly abatacept and ustekinumab, are also encouraging but less well advanced. We are at the dawn of a new era in GCA treatment, but uncertainties and opportunities abound.

Biologic Therapies for Giant Cell Arteritis

“…Given the hypothesised role of dual T-lymphocyte pathways, Th-1 and Th-17, in GCA, abatacept offers a plausible mechanism of action for disease treatment. 7 In a RCT, abatacept in conjunction with prednisolone demonstrated an increase in relapse-free survival at 12 months from 31% to 48% when compared to prednisolone monotherapy. 62 The median duration of remission was also greater in the abatacept group at 9.9 months versus 3.9 months in the placebo group.…”

“…Glucocorticoids have been the cornerstone of GCA treatment for the last 70 years. 7 They were first utilised in GCA by Horton in 1949 with formal confirmation of their efficacy by Shick in the 1950s. 24 , 25 While managing to induce clinical remission, high doses of prednisolone at 40–60mg per day, or even higher, are required initially, generally with prolonged use and frequent relapses over the coming 12–24 months.…”

“…Glucocorticoids have been the cornerstone of treatment in GCA for the past 70 years but relapses occur in almost 50% of treated patients. 7 , 12 While glucocorticoids can induce clinical remission, high doses and prolonged courses are required to suppress disease activity in GCA. There is a difficult balance between trying to offset the adverse consequences of long-term glucocorticoid use against the risk of GCA relapse.…”

The diagnosis and management of temporal arteritis

“…Assessment and evaluation of these agents continue in clinical trials. 139,[142][143][144] Currently, the efficacy of upadacitinib, a Janus-activated kinase 1 selective inhibitor, in the management of TA is being assessed in a worldwide trial which includes centres in Australia.…”

A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Sirukumab in the Treatment of Giant Cell Arteritis

“…Unfortunately, disease flare requiring adjustment of glucocorticoid dose occurs in 45–80% of patients [ 11 – 14 ], leading to prolonged glucocorticoid tapers and high glucocorticoid cumulative exposure and toxicity [ 15 – 17 ]. Glucocorticoid-related adverse events (AEs) can cause substantial morbidity [ 4 , 17 , 18 ] and are often serious [ 18 ]; therefore, there is need for remission maintenance with glucocorticoid-sparing medications in GCA [ 16 , 19 , 20 ].…”