How To Deal With Elevated Cholesterol - A Side Effect of New Rheumatoid Arthritis Treatments

Twenty years ago, rheumatoid arthritis was a condition that was generally progressive leading to increased disability and even early death.

With the advent of newer biologic therapies approximately seventeen years ago, most patients with rheumatoid arthritis will eventually achieve remission.

However, with that success comes a price. Because of the unique mechanism of action of biologic therapies- targeting specific points in the immune system- one of the logical problems has been side effects related to immune dysfunction.

Among these are an increased susceptibility to infection, increased chance of reactivation of tuberculosis, neurologic syndromes, increased insulin sensitivity in diabetics, elevation of blood lipids, and others.

One of the newer class of compounds that will be arriving on the biologic scene are the protein kinase inhibitor drugs. An example is the JAK - 3 group. These drugs block the signaling that occurs between the surface of immune cells and the nucleus of those cells. The end result is a "crippling" of the ability of the immune cell to over react.

What has been encouraging about these drugs are the following:

• They are oral
• They have an entirely different mode of action compared with the other biologics
• They also appear to work in patients that have failed tumor necrosis factor inhibitors

Probably, the JAK-3 drug that appears to be furthest along towards the FDA approval process is Pfizer's tofacitinib.

There are drawbacks, as expected. Tofacitinib has been associated with changes in liver and kidney function, elevated blood pressure, reduction in white blood cell counts, and elevation of blood lipids. The latter is not surprising since inflammation and lipid metabolism are intimately associated with each other.

The issue has been... "What do you do about it?"

The answer comes from a study done at the University of Glasgow. Professor Iain McInnes, professor of experimental medicine and rheumatology presented a study in which 111 patients with rheumatoid arthritis enrolled in a tofacitinib study were followed. During the open label part of the trial, patients taking tofacitinib received a cholesterol lowering statin drug. The group who received the stain drug had a 35 per cent lowering of blood lipids versus a 5.8 per cent increase in the placebo group.

The findings of the study were underscored by Dr. McInnes assertion that the elevation of lipids seen with tofacitinib could be reversed by adding the statin.

This is similar to the situation where it is sometimes necessary to add a statin to patients taking another rheumatoid arthritis drug, tocilizumab (Actemra), which also elevates lipids.