Onercept

During developmental age, differences in pharmacodynamic reactions to several drugs may reflect polymorphisms of genes encoding drug-transporting proteins, receptors, drug targets, and gene products, whose disturbed activity sometimes plays an important role in certain diseases. Administration of drugs with a narrow therapeutic index may quite easily be associated with changes in pharmacokinetics and development of adverse drug reactions, which occasionally may cause fatalities. In such cases, polypragmasy and resulting drug interactions may enhance effects of changes in drug-metabolizing enzymes' activities. Phenotyping and genotyping of patients slowly are finding their place in some therapeutic regimens used in clinical gastroenterology and hepatology. At present, some assays to measure, for example, thiopurine S-methyltransferase activity are already commercially available. Polymorphisms of CYP450 enzymes, interleukins, and altered gene expression play an important role in some patients' various gastrointestinal tract and liver diseases. Herbal drugs also affect proinflammatory and antiinflammatory cytokine and nitric oxide balance in the body. Therapeutic use of recombined proteins, such as infliximab, natalizumab, onercept, humanized antibody to integrin α-4 β-7, or IFN-β in some large-bowel diseases increased therapeutic efficacy. IFN-α used in the patients with chronic hepatitis C improved cellular immunity in these subjects and exerted antiviral activity. Practical application of progress in pharmacogenetics, pharmacokinetics, pharmacodynamics, and use of bioproducts in novel therapeutic regimens has opened therapeutic frontiers and increased clinical safety.

Adiponectin is an anti-inflammatory and potentially antiatherogenic molecule. Some recent reports suggest that tumour necrosis factor alpha (TNFalpha) blockade therapy increases circulating adiponectin levels, but data are sparse and inconsistent.

Data from a double-blind placebo controlled study of onercept in 126 patients with psoriatic arthritis (PsA) and from pre- and post-adalimumab treatment in 171 patients with rheumatoid arthritis (RA) were used to examine the effect of TNFalpha blockade therapy on adiponectin.

Despite expected associations of adiponectin with gender and baseline high-density lipoprotein cholesterol and triglyceride, adiponectin levels did not change over time with TNFalpha blockade therapy in either group. The mean+/-SD absolute change in adiponectin levels was -0.23+/-4.6 microg/ml in patients with PsA treated with combined onercept 50 mg and onercept 100 mg (vs placebo, p=0.60) and 0.28+/-3.23 microg/ml in patients with RA treated with adalimumab (vs baseline, p=0.66).

These results do not support a significant effect of TNFalpha blockade therapy on circulating adiponectin levels in patients with autoimmune disease.