A review of malignancies observed during efalizumab (Raptiva) clinical trials for plaque psoriasis.
BACKGROUND
Psoriasis is a chronic, incurable immune-mediated disease. Most therapies used for moderate to severe psoriasis are immunosuppressive. Agents that depress immune function, including traditional psoriasis therapies, have been associated with an increased incidence of malignancies. Efalizumab is a recombinant monoclonal immunoglobulin G1 (IgG1) antibody approved for use in psoriasis patients.


OBJECTIVE
To evaluate the incidence of malignancy in patients receiving efalizumab during clinical trials compared with placebo-treated patients, psoriasis patients from external cohorts and the general US population.


METHODS
Patient data were pooled from multiple phase III placebo-controlled, open-label efalizumab clinical trials, and the incidence rate of reported malignancies was calculated as a function of patient years of observation. The results for the efalizumab-treated patients were compared with the data on psoriasis patients from insurance claims databases and a registry of events in the general population.


RESULTS
The efalizumab- and placebo-treated patients had similar incidence rates of malignancy, including lymphoproliferative disease, solid tumor, malignant melanoma and nonmelanoma skin cancer. The incidence of nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, in patients receiving efalizumab or placebo was elevated relative to the external databases.


CONCLUSIONS
These results suggest that efalizumab treatment does not increase a patient's risk for malignancy. The difference observed with nonmelanoma skin cancer may be due to biases introduced by the clinical trial methodology. Additional patient observation is necessary to ascertain whether a link exists between efalizumab therapy and nonmelanoma skin cancer above that normally observed in psoriasis patients.
Leonardi
Craig L
CL
St. Louis University School of Medicine, St. Louis, Mo. 63117, USA. leonardi@certralderm.com
Toth
Darryl
D
Cather
Jennifer C
JC
Langley
Richard G B
RG
Werther
Winifred
W
Compton
Peter
P
Kwon
Paul
P
Wetherill
Graham
G
Curtin
Francois
F
Menter
Alan
A
D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced*; D011565:Psoriasis / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C472181:efalizumab