Need and value of targeted immunosuppressive therapy in giant cell arteritis

Abstract

Despite the heterogeneity of the giant cell arteritis (GCA) at the level of clinical manifestations and the cellular and molecular players involved in its pathogenesis, GCA is still treated with standardised regimens largely based on glucocorticoids (GC). Long-term use of high dosages of GC as required in GCA are associated with many clinically relevant side effects. In the recent years, the interleukin-6 receptor blocker tocilizumab has become available as the only registered targeted immunosuppressive agent in GCA. However, immunological heterogeneity may require different pathways to be targeted in order to achieve a clinical, immunological and vascular remission in GCA. The advances in the targeted blockade of various molecular pathways involved in other inflammatory and autoimmune diseases have catalyzed the research on targeted therapy in GCA. This article gives an overview of the studies with targeted immunosuppressive treatments in GCA, with a focus on their clinical value, including their effects at the level of vascular inflammation.

Analyses of plasma inflammatory proteins reveal biomarkers predictive of subsequent development of giant cell arteritis: a prospective study

“…It has been shown that Th1 cells may persist during treatment with glucocorticoids [ 28 ]. There is a great variety of potential future target therapies currently in clinical trials; the demonstration of such a Th1 cell signal may have implications for the use of targeted therapy [ 37 ].…”

Pathogenesis of giant cell arteritis with focus on cellular populations

“…Several targeted immunosuppressive drugs have been used as add-on to GCs, with the aim of reducing long term GC use and related toxicity ( 130 ). As expected based on the biology of IL-6, and its role in GCA, IL-6 inhibition by the anti-IL-6 receptor antibody tocilizumab is effective in GCA that has been verified by biopsy or large vessel imaging, and enables rapid GC tapering with reduced risk of relapse ( 13 ).…”

Giant cell arteritis and innovative treatments

“…It is used to treat psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis. it is an ongoing clinical trial, NCT04633447, that aims to evaluate, as its primary purpose, the efficacy of guselkumab compared to placebo, in combination with a 26-week GC taper regimen, in adult participants with new-onset or relapsing GCA [7]…”

“…It is used to treat psoriatic arthritis, generalized pustular psoriasis, and erythrodermic psoriasis. it is an ongoing clinical trial, NCT04633447, that aims to evaluate, as its primary purpose, the efficacy of guselkumab compared to placebo, in combination with a 26-week GC taper regimen, in adult participants with new-onset or relapsing GCA [7] Secukinumab Secukinumab, a fully human mAb that selectively inhibits IL-17A, was studied in phase two randomized controlled trial of 52 patients with new-onset or exacerbation GCA who were biologic-na€ ıve. Patients were randomized into two arms, one treated with secukinumab 300 mg, the other with a placebo administered weekly for 5 doses and then every 4 weeks until week 48, combined with a taper of prednisolone at 26 weeks.…”