Advances in the Treatment of Giant Cell Arteritis

Abstract

Giant cell arteritis (GCA) is the most common vasculitis among elderly people. The clinical spectrum of the disease is heterogeneous, with a classic/cranial phenotype, and another extracranial or large vessel phenotype as the two more characteristic patterns. Permanent visual loss is the main short-term complication. Glucocorticoids (GC) remain the cornerstone of treatment. However, the percentage of relapses with GC alone is high, and the rate of adverse events affects more than 80% of patients, so it is necessary to have alternative therapeutic options, especially in patients with worse prognostic factors or high comorbidity. MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review.

Comment on: Benchmarking tocilizumab use for giant cell arteritis

“…There was a low incidence of GCA relapse on TCZ, and visual symptoms were not seen as part of any flare. Data from other studies also show similar outcomes [ 3 ]. This supports the use of TCZ beyond 12 months; abrupt withdrawal of treatment can precipitate flare-up of GCA, with significant morbidity and mortality from the disease and glucocorticoids [ 3 ].…”

“…Data from other studies also show similar outcomes [ 3 ]. This supports the use of TCZ beyond 12 months; abrupt withdrawal of treatment can precipitate flare-up of GCA, with significant morbidity and mortality from the disease and glucocorticoids [ 3 ]. Biologic therapies for other rheumatic diseases are funded under National Institute for Health and Care Excellence guidance until the patient and clinician decide that it is appropriate to stop.…”

Faster steroid-free remission with Tocilizumab compared to Methotrexate in Giant Cell Arteritis: a real-life experience in two reference centres.

“…adding MTX in patients with high frequency of relapse resulted in a 3-fold reduction in the frequency of relapses per 10 person-years. Therefore, both TCZ and MTX allowed lower relapse rates in GCA patients [21], anyway the estimation of the effect size of treatment and the computation of number of patients needed to treat to prevent one GCA relapse remain a challenge due to differences between clinical practice and trials as well as early and late initiation of DMARDs [6].…”

Pros and cons of TNF inhibitors and tocilizumab in the treatment of large vessel vasculitis

“…Furthermore, there are some data on the association between elevated tissue TNF-α concentrations and disease activity (15). Three RCTs and a few other observational studies have investigated the use of TNFis in GCA, with negative or non-conclusive results (14,17), whereas some case series reported efficacy of TNFis (18,19). The first RCT was designed to evaluate the role of infliximab in maintaining remission in GCA (20).…”