JAK-inhibition as a therapeutic strategy for refractory primary systemic vasculitides

Editor – I read with interest the vasculitis update by Mooikhin Hng and colleagues who mention tociluzumab (anti-IL-6) as a therapeutic option in refractory giant cell arteritis (GCA), and wish to add that tocilizumab has been used successfully in refractory polyarteritis nodosa (PAN).^1,2 More importantly, patients with GCA who do not respond to biologics have few treatment options other than high doses of systemic corticosteroids.

These patients provide crucial learning experiences and the pressing need to understand pathogenesis of vasculitides in more detail. Inflammatory cytokines from effector T-cell subtypes allows self-sustained signalling in vasculitis and Janus-associated kinase inhibitors (JAKinibs; small molecules that inhibit JAK1, JAK2, JAK3 and Tyk2) have proven quite useful in controlling tissue inflammation in some refractory systemic vasculitis (supplementary material S1).^5–9 Immunophenotyping data in large vessel vasculitides show distinct characteristics between GCA and Takayasu’s arteritis (TAK), but also have similarities such as Th1, Th-17 and Tfh cells involved in both disease relapses and such knowledge may help with personalised therapies.³ The IL6/JAK/STAT3 axis in systemic sclerosis was one of the initial models where the efficacy of tofacitinib as a potential anti-fibrotic agent was recognised, and was then shown to reverse graft-versus-host disease indicating multiple effects in lowering inflammation. Even with JAKinibs, it is clear that deep understanding in redundancy of pathways is necessary before considering a particular inhibitor for a trial/experimental therapy.

Successful clinical trials of small molecules in vasculitides will shed new light into pathogenesis, but biologic use requires careful consideration of added risks (infection or malignancy) while effectiveness also means the duration of treatment may be indefinite. Working with SHARE (Single-Hub Access for Pediatric Rheumatology in Europe) or vasculitis foundations will help physicians understand these difficult diseases and in improving patients’ lives.

Supplementary material

Additional supplementary material may be found in the online version of this article at www.rcpjournals.org/clinmedicine:

S1 – Use of JAKinibs in vasculitides.