title: Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies.
abstract: Several biologics targeting different cytokines and receptors, including T-cell receptors, have been approved for psoriasis treatment. Siplizumab, a humanized anti-CD2 monoclonal antibody, may potentially provide an alternative therapy for psoriasis. Its safety profile and immunogenicity was examined in adults with plaque psoriasis. Two multicenter phase II randomized, double-blind, placebo-controlled studies: one tested two intravenous (I.V.) doses (0.012 and 0.04 mg/kg) of siplizumab every 2 weeks x 8 doses (124 patients); the second study tested three subcutaneous (S.C.) dose regimens of siplizumab (5 mg x 12 weeks, 5 mg x 6 weeks + placebo x 6 weeks, 7 mg x 4 weeks + placebo x 8 weeks), and placebo x 12 weeks (420 patients). Adverse events (AEs) and laboratory values were monitored. Immunogenicity was determined by anti-siplizumab antibodies quantification. In both studies, siplizumab exhibited an acceptable safety profile; most common AEs judged to be siplizumab related were lymphopenia, chills, and headache, reported at a higher frequency in the siplizumab-treated vs. placebo group. Siplizumab-related reductions in absolute lymphocyte count did not result in clinical evidence of immune suppression. Anti-siplizumab antibodies were detected after exposure to siplizumab; however, there was no evidence of an association between antibody development and AEs. Siplizumab exhibited an acceptable safety profile in adult patients with plaque psoriasis when administered as multiple I.V. or S.C. doses. Higher, clinically relevant doses of siplizumab would need to be tested to fully assess its safety.
authors.affiliation: Department of Medicine, Dalhousie University, Halifax, NS.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Langley
authors.forename: Kim
authors.initials: K
authors.lastname: Papp
authors.forename: Robert
authors.initials: R
authors.lastname: Bissonnette
authors.forename: Darryl
authors.initials: D
authors.lastname: Toth
authors.forename: Robert
authors.initials: R
authors.lastname: Matheson
authors.forename: Micki
authors.initials: M
authors.lastname: Hultquist
authors.forename: Barbara
authors.initials: B
authors.lastname: White
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized; D018801:CD2 Antigens / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018801:CD2 Antigens; D010919:Placebos; C544394:siplizumab