Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Tocilizumab for the Treatment of Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis) and Polymyalgia Rheumatica: A Case Series.

Unizony1,  Sebastian, Arias-Urdaneta1,  Luis, Miloslavsky2,  Eli, Arvikar1,  Sheila L., Khosroshahi1,  Arezou, Stone1,  John H.

Massachusetts General Hospital, Boston, MA
Massachusetts General Hopsital, Boston, MA

Background/Purpose:

Glucocorticoids (GC) are still the mainstay of therapy for giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and Takayasu arteritis (TA). A sizeable percentage of these patients experience disease exacerbations upon GC tapering and require repeated GC courses, resulting in prolonged GC exposure and adverse effects. Interleukin (IL)-6 is an attractive target for therapy in these conditions because patients with GCA, TA, and PMR have increased levels of this cytokine in their peripheral circulation and inflamed tissues, and serum IL-6 concentrations correlate with disease activity. We retrospectively assessed the outcomes of 7 patients with large-vessel vasculitis (GCA and TA) and PMR treated with tocilizumab (TCZ), an anti IL-6 receptor humanized monoclonal antibody.

Methods:

Patients with GCA, TA and PMR refractory to conventional therapy received monthly infusions of TCZ (8 mg/kg). Six subjects had failed at least one disease-modifying anti-rheumatic drug (methotrexate, azathioprine, or cyclophosphamide) or infliximab in addition to prednisone. Clinical improvement was assessed by evaluating symptoms of disease activity, inflammatory markers, ability to taper prednisone, and serial cross-sectional imaging when necessary before and during TCZ therapy. IL-6 level was measured at baseline and before each TCZ infusion.

Results:

Seven patients with GCA (n = 4), TA (n = 2), or PMR (n = 1) received TCZ. The mean duration of disease at the time of anti-IL6R therapy initiation was 18 months (range 11–28), and the mean follow up on TCZ was 5.1 months (range 4–6). Clinical signs of active inflammation disappeared in all patients following the initiation of TCZ. Within eight weeks, all subjects were able to taper their prednisone dose to a mean of less than 5 mg. Before TCZ, the patients had experienced an average of 2 flares per year. Since the initiation of TCZ, all patients have entered and maintained remission. The mean erythrocyte sedimentation rate (ESR) declined from 36.8 mm/h (range 10.6–66) to 7.6 mm/h (range 3.2–14.6) after the start of TCZ (P = 0.001). The mean C-reactive protein (CRP) concentration declined from 22.4 mg/L (range 5.6–32.7) at baseline to 2.8 mg/L (range 0.28–13.4) after anti-IL-6R therapy (P = 0.001). The mean prednisone dose was tapered from 18.3 mg/day (range 7–34.3) to 4.9 mg daily (range 0–6.5) following the initiation of TCZ (P = 0.007). Baseline IL-6 levels were elevated in all except one TA patient [Mean 13.8 pg/ml (range 2.8–18.4)]. In 6 cases, the IL-6 concentration increased after the initiation of TCZ [mean 128.3 pg/ml (range 30.9–308)]. Serial positron emission tomography (PET) studies in one TA patient revealed complete resolution of fluorodeoxyglucose uptake in the great vessels after 4 TCZ infusions. No patient required treatment with other immunosuppressive medications while on TCZ. Adverse effects related to TCZ included mild neutropenia (n=2) and transaminitis (n=3).

Conclusion:

IL-6 is important in the pathogenesis of GCA, TA and PMR. TCZ led to prompt clinical, serological and radiographic improvement in a group of patients with persistent disease who were unable to taper prednisone below acceptable doses despite concomitant second-line immunomodulatory agents.

To cite this abstract, please use the following information:
Unizony, Sebastian, Arias-Urdaneta, Luis, Miloslavsky, Eli, Arvikar, Sheila L., Khosroshahi, Arezou, Stone, John H.; Tocilizumab for the Treatment of Large Vessel Vasculitis (Giant Cell Arteritis, Takayasu Arteritis) and Polymyalgia Rheumatica: A Case Series. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1507
DOI:

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