Giant cell arteritis - Emerging treatments

Secukinumab

Secukinumab is a monoclonal antibody that selectively inhibits interleukin (IL)-17A. It has received approval for the treatment of psoriasis, psoriatic arthritis, non-radiographic axial spondyloarthritis, and ankylosing spondylitis in numerous countries, including the US and Europe. A phase 2 trial evaluated secukinumab in a double-blind, placebo-controlled study of 52 patients with either newly diagnosed or relapsing GCA.[89] Exclusion criteria included patients who had previously been treated with any biological agent including tocilizumab. The corticosteroid dose was tapered down over a 26-week period in both those assigned to secukinumab or placebo. Patients with active GCA had a higher sustained remission rate in the secukinumab group (70%) than in the placebo group (20%) at week 28, in combination with the corticosteroid taper regimen. This proof-of-concept study found that secukinumab was tolerated well with no new safety concerns.

Mavrilimumab

Mavrilimumab is a monoclonal antibody that inhibits human granulocyte-macrophage colony stimulating factor (GM-CSF), a proinflammatory cytokine. This results in functional changes including the reduction of infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex vivo cultured arteries from patients with GCA.[90] A phase 2 trial in 70 patients with biopsy-confirmed or imaging-confirmed GCA found mavrilimumab in combination with a 26-week corticosteroid taper was superior to placebo with a 26-week corticosteroid taper in reducing the the time to GCA flare and maintaining sustained remission.[91] Mavrilimumab was well tolerated, and the overall incidence of adverse events and serious adverse events was similar between groups.[91]

Janus kinase (JAK) inhibitors

JAK proteins mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic, and inflammatory diseases.[92][93] Baricitinib, an oral JAK inhibitor, selectively inhibits JAK1 and JAK2. It has been approved for the treatment of rheumatoid arthritis (as well as other indications). An open-label phase 2 pilot study demonstrated preliminary evidence of safety in patients with relapsing GCA.[94] A large phase 3 randomised, placebo-controlled trial evaluating upadacitinib (a JAK1 selective inhibitor also approved for the treatment of rheumatoid arthritis as well as other indications) in the treatment of GCA is ongoing.[95] JAK inhibitors are associated with potentially serious effects, and the US Food and Drug Administration (FDA) has recently added a warning to all currently approved JAK inhibitors, stating that these medications should be reserved for patients with rheumatoid arthritis who have had an inadequate response or intolerance to one or more tumour necrosis factor (TNF)-alpha inhibitors. This was based on the result of a surveillance study that compared the safety of tofacitinib and TNF-alpha inhibitors for the treatment of rheumatoid arthritis. The warning outlines the increased risk of death, major adverse cardiovascular events, malignancies, and thrombosis with JAK inhibitors compared with TNF-alpha inhibitors.[96] Although the surveillance study only compared tofacitinib with adalimumab, the FDA was concerned about a class effect, and the warning was also extended to baricitinib and upadacitinib.[92]