title: Subcutaneously administered efalizumab (anti-CD11a) improves signs and symptoms of moderate to severe plaque psoriasis.
abstract: BACKGROUND
  Phase I and Phase II studies in patients with moderate to severe plaque psoriasis demonstrated that intravenous (IV) efalizumab improved clinical signs and symptoms and was well tolerated.
  
  
  OBJECTIVE
  To determine if subcutaneous (SC) delivery of efalizumab improves chronic plaque psoriasis and demonstrates an acceptable safety profile.
  
  
  METHODS
  This was a Phase I, open-label, single- and multiple-dose, escalating-dose study. Subjects received a single dose of efalizumab (0.3 mg/kg/wk SC) or escalating multiple doses of efalizumab (0.50-2.0 mg/kg/wk SC). Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI), target lesion assessment, and Physician's Global Assessment (PGA). Safety was assessed by evaluating adverse events, clinical laboratory test results, physical examination results, immunologic responses, and vital signs.
  
  
  RESULTS
  PASI score, target lesion assessment, and PGA showed improvement of approximately 40%-60% in signs and symptoms of plaque psoriasis by day 56. Mean PASI scores were still declining at the end of the eight-week dosing period, suggesting that longer duration of treatment would be more effective. By day 91, mean PASI scores were 16.2 vs. 14.6 at day 56 in the 0.5-1.0-mg/kg/wk group and 11.7 vs. 10.1 in the 1.0-2.0-mg/kg/wk group. This demonstrates that, on average, patients maintained their treatment benefit during the 42-day followup period. Overall, there were considerably fewer adverse events than in previous IV studies. These consisted principally of mild to moderate headache, pain, and rhinitis. No allergic reactions were observed. Antibodies to efalizumab were observed in only one subject (2%) and did not have any clinical relevance.
  
  
  CONCLUSIONS
  The SC administration of eight weekly doses of efalizumab improves signs and symptoms of psoriasis. The treatment was safe and very well tolerated. In comparison to previously published results with IV efalizumab, SC administration of efalizumab improves overall safety and tolerability, with the additional advantage of greater convenience.
authors.affiliation: Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903-0019, USA. gottliab@UMDNJ.EDU
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lowe
authors.forename: William
authors.initials: W
authors.lastname: Shapiro
authors.forename: Charles
authors.initials: C
authors.lastname: Hudson
authors.forename: Ross
authors.initials: R
authors.lastname: Bright
authors.forename: Mark
authors.initials: M
authors.lastname: Ling
authors.forename: Anna
authors.initials: A
authors.lastname: Magee
authors.forename: Calvin O
authors.initials: CO
authors.lastname: McCall
authors.forename: Toivo
authors.initials: T
authors.lastname: Rist
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dummer
authors.forename: Patricia
authors.initials: P
authors.lastname: Walicke
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bauer
authors.forename: Mark
authors.initials: M
authors.lastname: White
authors.forename: Marvin
authors.initials: M
authors.lastname: Garovoy
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018845:CD11 Antigens; C472181:efalizumab