Tocilizumab for the treatment of large‐vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica

Abstract

Objective. The interleukin-6 pathway is up-regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ). Methods. Patients with GCA (n ‫؍‬ 7), TA (n ‫؍‬ 2), and PMR (n ‫؍‬ 1) received TCZ. Seven subjects had failed at least 1 second-line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross-sectional imaging when indicated clinically. Results. The mean followup time of this cohort since diagnosis was 27 months (range 16 -60 months). The patients were treated with TCZ for a mean period of 7.8 months (range 4 -12 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 7-34.3 mg/day) and 4.1 mg/day (range 0 -10.7 mg/day), respectively (P ‫؍‬ 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 11-68 mm/hour) to 7 mm/hour (range 2.2-11.3 mm/hour; P ‫؍‬ 0.0001). The adverse effects of TCZ included mild neutropenia (n ‫؍‬ 4) and transaminitis (n ‫؍‬ 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and mediumsized arteries. Conclusion. TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies.

Tocilizumab for the Treatment of Patients With Refractory Takayasu Arteritis

“…Adverse events: All patients tolerated the TCZ treatment without infusion reactions. Although TCZ has been reported to be associated with leukopenia and neutropenia, 22) we did not observe any leukopenia or neutropenia in our subjects. No gastrointestinal perforations were observed.…”

“…20) Urizony, et al treated 10 patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) with TCZ for a mean period of 7.8 months (range, 4-12 months). 22) All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range, 7-34.3 mg/day) and 4.1 mg/day (range, 0-10.7 mg/day), respectively.…”

“…Several recent studies have reported that IL-6 receptor (IL-6R) blockade with the IL-6R monoclonal antibody tocilizumab (TCZ) might be effective for the treatment of patients with refractory TA. [19][20][21][22] Since the mean time of TCZ administration in 3 recent pilot studies is a bit short (range, 3 to 12), [20][21][22] the safety and effi cacy of TCZ for patients with refractory TA need to be examined for longer periods. Here, we assessed the clinical, serological, and crosssectional imaging outcomes of 4 patients with refractory TA who were administered TCZ more than 24 times.…”

Targeting Interleukin-6 in Rheumatoid Arthritis

“…There are also case reports in regards to the use of tocilizumab in other auto-immune conditions such as giant cell arteritis [30,31], adult onset Still's disease [32] , systemic lupus erythematosus [33], ANCA-associated vasculitis [34], Behcet's disease [35,36], systemic sclerosis [37] and polymyositis [38]. These reports showed that tocilizumab was the salvage therapy used after disease resistance to various former drugs.…”

Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity

“…An open-label study and a retrospective review, along with some case reports and series, have shown promising results of anti-TNF treatment, but randomized trials are still lacking [126,127]. Some case series have also proposed tocilizumab and rituximab as efficacious agents [128,129].…”