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

Arthritis Care Res (Hoboken). 2012 Nov;64(11):1720-9. doi: 10.1002/acr.21750.

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 medium-sized 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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Dose-Response Relationship, Drug
  • Follow-Up Studies
  • Giant Cell Arteritis / drug therapy*
  • Glucocorticoids / administration & dosage
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Middle Aged
  • Polymyalgia Rheumatica / drug therapy*
  • Prednisone / administration & dosage
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Retrospective Studies
  • Takayasu Arteritis / drug therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • Immunosuppressive Agents
  • Receptors, Interleukin-6
  • tocilizumab
  • Prednisone