Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study

Christ, Lisa; Seitz, Luca; Scholz, Godehard; Sarbu, Adela-Cristina; Amsler, Jennifer; Bütikofer, Lukas; Tappeiner, Christoph; Kollert, Florian; Reichenbach, Stephan; Villiger, Peter M.

doi:10.1016/s2665-9913(21)00152-1

Cited by 42 publications

(26 citation statements)

References 14 publications

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“…It is well recognised that methotrexate impairs humoral responses to both influenza and pneumococcal vaccines, 1,2 and a temporary discontinuation of therapy for 2 weeks enhances influenza vaccine immunogenicity in patients with rheumatoid arthritis. 3 These data were used as a surrogate for COVID-19 vaccination responses, prompting the American College of Rheumatology (ACR) to recommend temporary interruption of methotrexate for 1 week after each vaccine dose. 4 The degree to which this pause will translate to enhanced COVID-19 vaccine responses is unclear, but data are rapidly accumulating.…”

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confidence: 99%

“…First, patients with these diseases often have an elevated inflammatory setpoint and might be more likely to develop secondary hyperinflammatory syndromes. 3 Second, immunomodulatory therapies used in patients with systemic rheumatic diseases might variably affect susceptibility to COVID-19 and its associated hyperinflammatory syndrome. For example, some therapies, such as tumour necrosis factor inhibitors, have been posited to temper complications associated with COVID-19 hyperinflammation.…”

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confidence: 99%

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Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Connolly

Paik

2021

The Lancet Rheumatology

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1 Ribeiro ACM, Guedes LKN, Moraes JCB, et al. Reduced seroprotection after pandemic H1N1 influenza adjuvant-free vaccination in patients with rheumatoid arthritis: implications for clinical practice. Ann Rheum Dis 2011; 70: 2144-47. 2 Kapetanovic MC, Roseman C, Jönsson G, et al. Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum 2011; 63: 3723-32. 3 Park JK, Lee YJ, Shin K, et al. Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.

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Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Connolly

Paik

2021

The Lancet Rheumatology

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“…Whether a GC-free induction of remission was possible with tocilizumab was not yet clear. To address this question, a recent investigator-initiated, single-arm, open-label trial included 18 new-onset GCA patients who received 500 mg methylprednisolone intravenously for three consecutive days, combined with a single infusion of tocilizumab (8 mg/kg), followed by tocilizumab s.c. 1x/week 26. The primary endpoint of an early remission at 4 weeks was not reached.…”

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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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“…Results from several trials in the coming years will hopefully answer some of these questions. The GCA treatment with ultra-short GC and tocilizumab (GUSTO) trial (NCT03745586) showed that a three-day course of high dose glucocorticoids had adequate rates of remission in 13 of 18 patients, comparable to the standard 24-week taper course ( 129 ). Another 30-patient open-label trial showed that 12 months of tocilizumab with initial two months prednisone taper was able to induce remission in 77% of patients by 12 months ( 130 ).…”

Section: Discussionmentioning

confidence: 99%

Current developments in the diagnosis and treatment of giant cell arteritis

Szekeres

Othman

2022

Front. Med.

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Giant cell arteritis is the most common vasculitis in adults above 50 years old. The disease is characterized by granulomatous inflammation of medium and large arteries, particularly the temporal artery, and is associated acutely with headache, claudication, and visual disturbances. Diagnosis of the disease is often complicated by its protean presentation and lack of consistently reliable testing. The utility of color doppler ultrasound at the point-of-care and FDG-PET in longitudinal evaluation remain under continued investigation. Novel techniques for risk assessment with Halo scoring and stratification through axillary vessel ultrasound are becoming commonplace. Moreover, the recent introduction of the biologic tocilizumab marks a paradigm shift toward using glucocorticoid-sparing strategies as the primary treatment modality. Notwithstanding these developments, patients continue to have substantial rates of relapse and biologic agents have their own side effect profile. Trials are underway to answer questions about optimal diagnostic modality, regiment choice, and duration.

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Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study

Cited by 42 publications

References 14 publications

Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Impact of methotrexate on first-dose COVID-19 mRNA vaccination

Need and value of targeted immunosuppressive therapy in giant cell arteritis

Current developments in the diagnosis and treatment of giant cell arteritis

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