Session Title: Vasculitis II
Session Type: Abstract Submissions (ACR)
A sizeable percentage of giant cell arteritis (GCA) patients experience disease relapse upon glucocorticoid (GC) tapering, and a clearly effective GC-sparing alternative has not been identified. Interleukin (IL)-6 contributes to the pathogenesis of GCA and represents a target for therapy.
Retrospective study of 12 relapsing GCA patients treated the IL-6 receptor (IL-6R) antagonist tocilizumab (TCZ). Clinical outcomes evaluated were number of flares, ability to taper GC without disease exacerbation and safety.
Serum levels of the T-helper (TH)1-, TH17- and regulatory T cell-related cytokines IL-17, IFN-γ, IL-12, IL-6, IL-21, IL-22, IL-23, IL-1β, TNF-α and IL-10 were analyzed by Luminex in a group of patients who achieved remission on TCZ with or without low dose GC (n = 5), and compared with those of a group whose disease was controlled with GC monotherapy (n = 5)
Baseline characteristics: The mean follow-up of this cohort since diagnosis was 37 months (range 17-70). The mean duration of the disease at the time of TCZ initiation was 19.5 months (range 4-53). Eight subjects had failed at least one immunosuppressant (i.e., methotrexate), and four had contraindications for the use of GC.
Clinical response and GC-sparing effects: TCZ (4 mg/Kg, n = 3 and 8 mg/Kg, n = 9) was given in monthly infusions for a mean period of 16 months (range 5-26). Before and during IL-6R blockade, the patients experienced an average of 2.7 (95% CI 2-3.5) and 0.6 (95% CI 0-1.2) disease exacerbations per year, respectively (P = 0.0006). The mean daily prednisone dose of the cohort decreased from 24 mg (95% CI 15-33.5) at the time of TCZ initiation to 7 mg (95% CI 0.7-14) by the time of last evaluation (P = 0.01). On TCZ, 7 subjects maintained disease remission for a mean time of 17.5 months (range 8-26), and 5 patients flared after an average of 11 months of therapy (range 2-24). The mean prednisone dose at the time of flare in these 5 patients was 4.5 mg/day. One subject relapsed after TCZ discontinuation. Currently, 6 patients are taking ≤5 mg/day of prednisone and 3 patients are off GC. As expected, inflammatory markers normalized and IL-6 levels significantly increased in all patients receiving TCZ.
Safety: Adverse events attributable in part to TCZ included leucopenia (n = 5), transaminitis (n = 8), and pneumonia (n = 1). Autopsy on one patient who died from an unrelated cause revealed persistent vasculitis.
Cytokine analysis:There was a non-statistically significant difference in the serum cytokine concentrations measured by multiplex bead-based Luminex assays. Patients whose disease was maintained in remission on TCZ with or without low dose GC (mean prednisone dose 5 mg/day) tended to have lower levels of IL-12, IFN-γ, and IL-17, and higher levels of IL-10 than subjects in remission with GC monotherapy (mean prednisone dose 16 mg/day). IL-1β and IL-6 increased during IL-6R blockade. IL-21, IL-22, and IL-23 were not detected in the majority of cases, and the concentration of TNF-α was similar in both groups.
TCZ led to a significant reduction in the flare rate and GC requirement of a group of patients with highly relapsing GCA. A randomized-controlled trial of TCZ for the treatment of GCA is currently ongoing.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/long-term-use-of-tocilizumab-for-the-treatment-of-giant-cell-arteritis/