New drugs: Ustekinumab, tocilizumab, and telavancin hydrochloride.

Agent for psoriasis Psoriasis is an autoimmune disease characterized by inflammatory skin lesions/plaques that are often painful and can be debilitating. Although milder forms of psoriasis can often be effectively treated with topical corticosteroids and other topically applied agents, moderate to severe forms of the disease often require systemic therapy or phototherapy. Advances in the treatment of psoriasis have included the use of medications that have immunosuppressive activity such as methotrexate; cyclosporine; alefacept (Amevive), which interferes with T-cell activation; and the tumor necrosis factor (TNF) antagonists etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade). Interleukin (IL)-12 and -23 are naturally occurring proteins that are involved in the psoriatic inflammatory process by activating natural killer cells and T-cells. Ustekinumab (Stelara—Centocor Ortho Biotech) is a human monoclonal antibody that is the first medication to selectively bind to these cytokines. It binds with high affinity to the p40 protein subunit of IL-12 and -23, thereby preventing them from binding with their respective receptors and resulting in a decreased inflammatory response. The new drug is indicated for the treatment of adult patients with moderate or severe plaque psoriasis who are candidates for phototherapy or systemic therapy. The efficacy of ustekinumab was demonstrated in two placebo-controlled studies in which approximately 70% of the patients treated with the drug experienced at least a 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) after two doses compared with less than 5% of those receiving placebo. In one of these studies, patients were evaluated for a longer period and approximately 90% of the patients having an initial reduction in PASI score of at least 75% maintained this response through 1 year of treatment. In a study in which ustekinumab was compared with etanercept, 68% and 74% of patients treated with 45 and 90 mg ustekinumab dosages, respectively, experienced at least a 75% reduction in PASI score compared with 57% of the patients treated with etanercept. Of the patients who did not have a response to etanercept, almost 50% had at least a 75% reduction in PASI score within 12 weeks following subsequent treatment with ustekinumab. The risks and adverse events associated with the use of ustekinumab are generally similar to those of the TNF antagonists. Of greatest concern is the potential for serious infection, and treatment with ustekinumab should not be initiated in patients with a clinically important active infection. If a serious infection develops during treatment, treatment with ustekinumab should be suspended until the infection is adequately treated or resolves. Patients should be evaluated for the presence of a tuberculosis (TB) infection before initiating treatment with ustekinumab. The drug should not be used in patients with active TB, and if latent TB is identified, antitubercular treatment should be initiated before administering ustekinumab. Individuals who have a genetic deficiency of IL-12 and -23 are at greater risk of disseminated infections caused by mycobacteria, salmonella, and Bacillus CalmetteGuerin (BCG) vaccinations. Whether patients experiencing inhibition of these ILs as a result of ustekinumab treatment will be more vulnerable to these infections is not known. However, it is recommended that BCG vaccines not be administered during treatment with ustekinumab or for 1 year before initiating treatment or 1 year following discontinuation of treatment. Before initiating treatment with ustekinumab, patients should have already received the immunizations recommended by current guidelines, and they should not receive live vaccines during treatment. Like other medications that exhibit an immunosuppressant action, ustekinumab may increase the risk of malignancies. The safety of its use in patients who have a known malignancy or a history of malignancy has not been evaluated. In the clinical studies with ustekinumab, which included more than 3,500 patients, one patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Treatment was discontinued, and the patient fully recovered with appropriate management. If neurologic or other manifestations suggestive of RPLS occur in patients treated with the new drug, therapy should be discontinued. The adverse events experienced most often in the clinical studies with ustekinumab include nasopharyngitis (7%), headache (5%), upper respiratory tract infection (4%), and fatigue (3%). As with all biological therapies, a concern exists regarding immunogenicity. Because ustekinumab has such a long half-life and its presence in the blood interferes with the antibody assay, many of the test results were inconclusive. Of the approximately 2,000 patients screened, less than 5% had positive antibody results, indicating a low risk of immunogenicity. Ustekinumab is classified in Pregnancy Category B and should only be