Long-term follow-up of relapsing/refractory anti-neutrophil cytoplasm antibody associated vasculitis treated with the lymphocyte depleting antibody alemtuzumab (CAMPATH-1H).
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.


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 micromol/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.
Walsh
M
M
Vasculitis Clinic, Box 118, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. mwwalsh@ucalgary.ca
Chaudhry
A
A
Jayne
D
D
D000328:Adult; D000074323:Alemtuzumab; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018791:CD4 Lymphocyte Count; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab