Ustekinumab: new drug. Suspicion of carcinogenicity: too great a risk for psoriasis patients.
(1) For adults with plaque psoriasis, after failure of topical symptomatic treatments and PUVA therapy, several systemic immunosuppressive agents are acceptable for severe disease: methotrexate, then ciclosporin, and possible a TNF alpha antagonist (etanercept, etc.); (2) Ustekinumab is an inhibitor of interleukins 12 and 23, which are believed to be implicated in the onset of psoriasis. It is authorized in the European Union for patients who fail to respond to conventional systemic treatments; (3) In one trial with a low level of evidence (single-blind), 2 subcutaneous injections of ustekinumab at an interval of 4 weeks appeared to be statistically more effective than twice-weekly subcutaneous injections of etanercept for 12 weeks. More patients achieved a 75% reduction in the score most widely used to evaluate the extent and intensity of plaque psoriasis lesions (PASI score): about 71% versus 57%. The results beyond this period have not been reported; (4) Two randomised, double-blind, placebo-controlled trials in a total of 1996 patients showed that at least two-thirds of patients treated with ustekinumab achieved at least a 75% reduction in their PASI score versus fewer than 4% with placebo; (5) In animal studies, interleukin 12 and 23 inhibitors cause cancer. There is therefore a high risk of cancer developing during prolonged treatment with ustekinumab; (6) The main adverse effects identified in clinical trials include infections, injection-site reactions, psychological disorders and development of anti-ustekinumab antibodies; (7) There is insufficient follow-up to evaluate the cardiac risks associated with ustekinumab; (8) As maintenance therapy, ustekinumab is administered as one subcutaneous injection every 12 weeks. This practical advantage compared to TNF alpha antagonists must be weighed against the risks inherent in prolonged immunosuppression; (9) In summary, for symptomatic relief of patients whose psoriasis poses major problems despite treatment with methotrexate or ciclosporin, in the absence of a better alternative, it is better to use a TNF alpha antagonist and to avoid exposing patients to the risks associated with ustekinumab, particularly its carcinogenic risk.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D000068800:Etanercept; D005060:Europe; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000139:chemically induced; D011565:Psoriasis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D053759:Interleukin-23; D018124:Receptors, Tumor Necrosis Factor; D018664:Interleukin-12; D000069549:Ustekinumab; D000068800:Etanercept