Newer Biological Agents in the Treatment of Rheumatoid ArthritisNurmohamed, Michael
doi: 10.2165/11318290-000000000-00000pmid: 19791825
Recently, three new biological agents, rituximab, abatacept and tocilizumab, have become available for the treatment of rheumatoid arthritis (RA) in patients with active disease, who have not responded to at least one disease-modifying antirheumatic drug (DMARD). Rituximab is an anti-CD20 monoclonal antibody, abatacept modulates T-cell activation and tocilizumab is an interleukin-6 receptor antagonist. Clinical studies with these agents have demonstrated that they are effective in RA patients with moderate to active disease, who have not responded to treatment with at least one DMARD and/or tumour necrosis factor (TNF) inhibitor. Thus far, there is no convincing evidence to show that one of these three new drugs has a superior efficacy over the others or that they have other benefits compared with the TNF inhibitors. The use of rituximab, instead of another TNF inhibitor, might be an option in patients who have not responded to TNF blockade. Abatacept could also be considered, but this has not yet been formally tested. A practical advantage of tocilizumab is that it may be administered as a first-line biological agent.
African American Kidney Transplantation SurvivalMalat, Gregory; Culkin, Christine; Palya, Aniruddha; Ranganna, Karthik; Kumar, Mysore
doi: 10.2165/11318570-000000000-00000pmid: 19791826
Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation.
SaxagliptinDhillon, Sohita; Weber, Juliane
doi: 10.2165/11201170-000000000-00000pmid: 19791828
▲ Saxagliptin and its active metabolite M2 are dipeptidyl peptidase-4 inhibitors that improve glycaemic control by preventing the inactivation of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. This increases GLP-1 levels, stimulates insulin secretion and reduces postprandial glucagon and glucose levels.
▲ In well designed, 24-week trials in treatmentnaive patients with type 2 diabetes mellitus, monotherapy with oral saxagliptin 2.5 or 5mg once daily significantly improved glycaemic control, as measured by mean glycosylated haemoglobin (HbA1c) levels, relative to placebo.
▲ In large, well designed, 24-week trials, combination therapy with saxagliptin 5 mg once daily plus metformin significantly improved HbA1c levels relative to single-agent saxagliptin or metformin in treatment-naive patients; in treatment-experienced patients with inadequate glycaemic control, the addition of saxagliptin 2.5 or 5 mg once daily to metformin, glyburide or a thiazolidinedione, significantly improved HbA1c levels relative to continued use of existing monotherapy.
▲ Saxagliptin as monotherapy or in combination with other oral antihyperglycaemics was generally well tolerated, with most adverse events being of mild to moderate severity. In clinical trials, the incidence of hypoglycaemic events in patients receiving saxagliptin was generally similar to that in patients receiving placebo or other oral antihyperglycaemic agents.
▲ Saxagliptin therapy was not associated with an increased risk of cardiovascular events according to pooled data from eight clinical trials. Saxagliptin generally had a weight-neutral effect.
EverolimusGarnock-Jones, Karly; Keating, Gillian
doi: 10.2165/11203770-000000000-00000pmid: 19791829
▲ Everolimus is an orally administered, targeted therapy indicated for the treatment of advanced renal cell carcinoma. It inhibits the mammalian target of rapamycin, an integral component of multiple pathways involved in cell growth and proliferation.
▲ Median progression-free survival was significantly longer with everolimus 10 mg once daily than with placebo in both second interim (4.0 vs 1.9 months) and updated (4.9 vs 1.9 months) analyses of a randomized, double-blind, placebo-controlled, multicentre, phase III trial in patients with metastatic renal cell carcinoma that had progressed while receiving sunitinib and/or sorafenib treatment.
▲ At the second interim analysis, median overall survival was 8.8 months for placebo recipients; at this analysis, overall survival had not yet been reached for everolimus recipients.
▲ With regard to objective response at the second interim analysis, 64% of everolimus and 32% of placebo recipients had either a partial response (1% and 0%) or stable disease (63% and 32%).
▲ The tolerability profile of everolimus was largely manageable in the phase III trial, with most treatment-related adverse events being of grade 1 or 2 severity.