title: Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection.
abstract: OBJECTIVE
  To investigate the dose tolerance and potential clinical activity of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H (C1H), in patients with active, refractory rheumatoid arthritis (RA).
  
  
  METHODS
  Thirty adult patients with active, refractory RA were treated in an open-label, 3-center, dose-escalation study of subcutaneously injected C1H. Six patients were assigned to each of 5 dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily injections of C1H over a 12-day period.
  
  
  RESULTS
  Side effects occurred primarily during the first 1-2 days of dosing, and included mild fever, chills, nausea, vomiting, headache, and, in a minority of patients, hypotension. All patients developed some discomfort at the injection site. Self-limited infections occurred in 5 patients during the 6-month study period. Peripheral blood lymphocyte counts fell promptly after initial dosing and recovered slowly, usually over 2-3 months. Serum antibodies to C1H developed in 54% of patients following treatment. Clinical improvement was observed in 56% of patients, based on the composite Paulus criteria, with a median time-to-response of 22 days and a median response duration of 32 days.
  
  
  CONCLUSIONS
  C1H is a lymphocyte-depleting antibody that exhibits biologic potency when administered subcutaneously to patients with refractory RA. Its use is associated with mild to moderate toxicity and short-term amelioration of disease activity.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Matteson
authors.forename: D E
authors.initials: DE
authors.lastname: Yocum
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
authors.forename: A A
authors.initials: AA
authors.lastname: Achkar
authors.forename: M S
authors.initials: MS
authors.lastname: Thakor
authors.forename: M R
authors.initials: MR
authors.lastname: Jacobs
authors.forename: A E
authors.initials: AE
authors.lastname: Hays
authors.forename: C K
authors.initials: CK
authors.lastname: Heitman
authors.forename: J M
authors.initials: JM
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000951:Antigens, Neoplasm; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D000074301:CD52 Antigen; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006023:Glycoproteins; D006801:Humans; D007279:Injections, Subcutaneous; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins