Treatment of Giant Cell Arteritis (GCA)

Abstract

Giant cell arteritis (GCA) is the most frequent primary large-vessel vasculitis in individuals older than 50. Glucocorticoids (GCs) are considered the cornerstone of treatment. GC therapy is usually tapered over months according to clinical symptoms and inflammatory marker levels. Considering the high rate of GC-related adverse events in these older individuals, immunosuppressive treatments and biologic agents have been proposed as add-on therapies. Methotrexate was considered an alternative option, but its clinical impact was limited. Other immunosuppressants failed to demonstrate a significant favourable benefit/risk ratio. The approval of tocilizumab, an anti-interleukin 6 (IL-6) receptor inhibitor brought significant improvement. Indeed, tocilizumab had a noticeable effect on cumulative GCs’ dose and relapse prevention. After the improvement in pathophysiological knowledge, other targeted therapies have been proposed, with anti-IL-12/23, anti-IL-17, anti-IL-1, anti-cytotoxic T-lymphocyte antigen 4, Janus kinase inhibitors or anti-granulocyte/macrophage colony stimulating factor therapies. These therapies are currently under evaluation. Interestingly, mavrilimumab, ustekinumab and, to a lesser extent, abatacept have shown promising results in phase 2 randomised controlled trials. Despite this recent progress, the value, specific condition and optimal application of each treatment remain undecided. In this review, we discuss the scientific rationale for each treatment and the therapeutic strategy.

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

“…European League Against Rheumatism (EULAR) recommendations [4] assert to add GC-sparing therapies for relapsing GCA patients or patients who have an increased risk of developing GC-related comorbidities. However, there is a trade-off to consider: a rapid reduction in GC dosage is linked to higher risk of relapses, while a delayed reduction in GC dose can result in a greater burden of side effects [11]. MTX and TCZ are the most commonly prescribed drugs for steroid-sparing treatment in practice [12], and there have been still no direct studies comparing treatment with MTX and TCZ in GCA.…”

New Insights into the Pathogenesis of Giant Cell Arteritis: Mechanisms Involved in Maintaining Vascular Inflammation

“…The most recent work also showed the involvement of processes leading to the amplification and/or maintenance of inflammation and vascular remodeling, such as regulatory T response defects (regulated by IL-6), GM-CSF and the roles of macrophages and NOTCH, along with probably a major role of arterial wall resident cells. These mechanisms identify targets for the development of new therapeutics such as tocilizumab [ 77 ], and more recently, mavrilimumab [ 162 ], secukinumab [ 167 ], JAK inhibitors [ 168 ], abatacept [ 137 ] and ustekinumab [ 169 , 170 , 171 ] ( Figure 3 ) [ 172 ].…”

Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure–Activity Relationships and Molecular Docking

“…83 Through research, it has been determined that using IL-6 inhibitors, specifically tocilizumab, instead of continuously using corticosteroid is an effective way to keep GCA in remission. 88 3.1.3. COVID-19.…”

“…IL-6 inhibitors are thought to reduce vascular inflammation through a variety of mechanisms, including modification of the upstream differentiation of autoreactive cells, which increases Treg cell production and targets the downstream components of the inflammatory signaling process . Through research, it has been determined that using IL-6 inhibitors, specifically tocilizumab, instead of continuously using corticosteroid is an effective way to keep GCA in remission …”