Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

Koster, Matthew J.; Crowson, Cynthia S.; Giblon, Rachel; Jaquith, Jane; Duarte‐García, Alí; Matteson, Eric L.; Weyand, Cornelia M.; Warrington, Kenneth J.

doi:10.1136/annrheumdis-2021-221961

Cited by 57 publications

(45 citation statements)

References 46 publications

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“…In a recent phase two, open-label study, 15 patients with relapsing GCA were treated with 4 mg baricitinib daily for 52 weeks in addition to a standardised GC taper 41. The primary endpoint was the safety of treatment.…”

Section: Cytokine-targetingmentioning

confidence: 99%

Need and value of targeted immunosuppressive therapy in giant cell arteritis

2022

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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.

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Section: Cytokine-targetingmentioning

confidence: 99%

Need and value of targeted immunosuppressive therapy in giant cell arteritis

2022

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“…With regard to shingles, it has been reported that VZV is a contributing factor in the development of GCA ( 63 , 64 ) and is considered extremely high-risk in elderly patients with GCA. In the study of baricitinib for GCA described above, it was reported that the live-attenuated zoster vaccine did not prevent the onset of shingles ( 49 ). It has been reported that recombinant adjuvanted zoster vaccine can suppress the onset of herpes zoster at a high rate in RA patients ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

“…In line with these data from basic research, several case reports describing the efficacy of JAK inhibitors on LVV have been published ( 29 , 43 – 48 ). Very recently, baricitinib, an inhibitor of JAK1 and JAK2, was reported to be effective against relapsing GCA in a prospective open-label study ( 49 ). Although the number of enrolled patients was small, the high remission induction and steroid withdrawal rates suggest that this treatment is promising for GCA.…”

Section: Jak Inhibitors For Vasculitismentioning

confidence: 99%

Perspectives of JAK Inhibitors for Large Vessel Vasculitis

Watanabe

Hashimoto

2022

Front. Immunol.

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Vasculitis is an inflammation of the blood vessels caused by autoimmunity and/or autoinflammation, and recent advances in research have led to a better understanding of its pathogenesis. Glucocorticoids and cyclophosphamide have long been the standard of care. However, B-cell depletion therapy with rituximab has become available for treating antineutrophil cytoplasmic antibody-associated vasculitis (AAV). More recently, avacopan, an inhibitor of the complement 5a receptor, was shown to have high efficacy in remission induction against AAV. Thus, treatment options for AAV have been expanded. In contrast, in large vessel vasculitis (LVV), including giant cell arteritis and Takayasu arteritis, tocilizumab, an IL-6 receptor antagonist, was shown to be effective in suppressing relapse and has steroid-sparing effects. However, the relapse rate remains high, and other therapeutic options have long been awaited. In the last decade, Janus kinase (JAK) inhibitors have emerged as therapeutic options for rheumatoid arthritis (RA). Their efficacy has been proven in multiple studies; thus, JAK inhibitors are expected to be promising agents for treating other rheumatic diseases, including LVV. This mini-review briefly introduces the mechanism of action of JAK inhibitors and their efficacy in patients with RA. Then, the pathophysiology of LVV is updated, and a rationale for treating LVV with JAK inhibitors is provided with a brief introduction of our preliminary results using a mouse model. Finally, we discuss the newly raised safety concerns regarding JAK inhibitors and future perspectives for treating LVV.

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“…Fifteen relapsing GCA patients were enrolled in an open-label pilot study and preliminary results demonstrated evidence of both efficacy and safety. Discontinuation of glucocorticoids was allowed in the majority of patients with relapsing GCA but larger trials are needed to confirm these results ( 196 ). Finally, the inhibition of the complement pathway with avacopan (anti-C5a receptor) in AAV showed promising results but its effects on the Th17 pathway have to be characterized ( 197 ).…”

Section: Targeting Il-17 and Th17 Cells In Vascular Inflammationmentioning

confidence: 99%

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

2022

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The involvement of IL-17A in autoimmune and inflammatory diseases has prompted the development of therapeutic strategies to block the Th17 pathway. Promising results came from their use in psoriasis and in ankylosing spondylitis. IL-17A acts on various cell types and has both local and systemic effects. Considering the premature mortality observed during chronic inflammatory diseases, IL-17A action on vascular cells was studied. Both in vitro and in vivo results suggest that this cytokine favors inflammation, coagulation and thrombosis and promotes the occurrence of cardiovascular events. These observations led to study the role of IL-17A in diseases characterized by vascular inflammation, namely allograft rejection and vasculitis. Increased circulating levels of IL-17A and histological staining reveal that the Th17 pathway is involved in the pathogenesis of these diseases. Vasculitis treatment faces challenges while the use of steroids has many side effects. Regarding results obtained in giant cell arteritis with IL-6 inhibitors, a cytokine involved in Th17 differentiation, the use of anti-IL-17 is a promising strategy. However, lessons from rheumatoid arthritis and multiple sclerosis must be learnt before targeting IL-17 in vasculitis, which may be culprit, consort or both of them.

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Baricitinib for relapsing giant cell arteritis: a prospective open-label 52-week pilot study

Cited by 57 publications

References 46 publications

Need and value of targeted immunosuppressive therapy in giant cell arteritis

Need and value of targeted immunosuppressive therapy in giant cell arteritis

Perspectives of JAK Inhibitors for Large Vessel Vasculitis

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

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