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Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H)
  1. M Walsh1,2,
  2. A Chaudhry2,
  3. D Jayne2
  1. 1
    Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
  2. 2
    Vasculitis and Lupus Clinic, Addenbrooke’s Hospital, Cambridge, UK
  1. M Walsh, Vasculitis Clinic, Box 118, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK; mwwalsh{at}ucalgary.ca

Abstract

Objective: Lymphocytes are a contributor to the pathogenesis of anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis (AASV). Conventional immunosuppressive therapy is associated with high rates of relapse and toxicity. Humanised monoclonal anti-CD52 antibodies (alemtuzumab, CAMPATH-1H) selectively deplete lymphocytes. We present long-term follow-up results of patients with relapsing/refractory AASV treated with CAMPATH-1H.

Patients and methods: Between 1991 and 1999, 71 patients with refractory or relapsing AASV received CAMPATH-1H at Addenbrooke’s Hospital, Cambridge, UK. Other immunosuppressive drugs were discontinued and prednisolone was tapered to 10 mg/day.

Results: The mean follow-up time was 5 years. In all, 79% had previously received cyclophosphamide (median dose 150 g). At the time of treatment, 42% had renal involvement (median creatinine for the cohort 101 μmol/litre excluding six patients who were dialysis dependent) and 18% were critically ill from AASV and required the intensive care unit. A total of 60 patients (85%) obtained a remission after treatment with CAMPATH-1H but 43 relapsed (median 9.2 months); 24 had a remission greater than 1 year, of which 10 had a remission of at least 3 years. A total of 31 patients died (median survival time of 106 months). Age >50 years, dialysis dependency and the development of a severe infection at the time of treatment were associated with an increased risk of death in multivariable analysis. Adverse events were common; 28 patients developed an infection, 3 malignancy and 8 thyroid disease.

Conclusions: CAMPATH-1H induced remission in most patients with difficult to treat AASV. However, relapse and adverse events were common. Further study of CAMPATH-1H as an induction agent in AASV is warranted.

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Footnotes

  • Funding: MW is supported by fellowship grants from the Kidney Research Scientist Core Education Training Program, Alberta Heritage Foundation for Medical Research, and the Royal College of Physicians and Surgeons of Canada.

  • Competing interests: DJ has received research funding from Genzyme.

  • Ethics approval: Ethics approval was obtained.

  • All patients in this study received CAMPATH 1-H under the supervision of Professor C M Lockwood who pioneered this and other immunotherapies in vasculitis.

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