Biologic Bullets the New Model for Treating Rheumatoid Arthritis

Prior to the development of newer biologic medications, rheumatologists were relegated to using disease modifying anti-rheumatic drugs (DMARDS) to treat rheumatoid arthritis (RA) These DMARDS (drugs such as methotrexate, hydroxychloroquine [Plaquenil], sulfasalazine [Azulfidine]), were and continue to be helpful in reducing signs and symptoms of disease but do not have the ability to place the disease into remission

Prior to the development of newer biologic medications, rheumatologists were relegated to using disease modifying anti-rheumatic drugs (DMARDS) to treat rheumatoid arthritis (RA).

These DMARDS (drugs such as methotrexate, hydroxychloroquine [Plaquenil], sulfasalazine [Azulfidine]), were and continue to be helpful in reducing signs and symptoms of disease but do not have the ability to place the disease into remission.

Approximately 15 years ago, though, the landscape shifted with the advent of biologic therapy, targeted therapies that act on specific targets in the immune cascade.

The measurement of disease activity as well as treatment effectiveness has shifted from purely measuring inflammation to also using devices such as health related quality of life questionnaires.

The use of these questionnaires provides a glimpse into a patient?s physical function, subjective sensation of pain, emotional health, social function, and fatigue.

While these questionnaires are subjective, objective measures of disease are also being tallied. In addition to blood markers such as C-reactive protein and erythrocyte sedimentation rate (ESR), which have been old-time stand-bys, clinical measurements such as disease activity score (DAS) which incorporate a combination of objective joint measures of inflammation plus blood markers, have allowed more precise evaluations of a patient?s status.

Also, the use of diagnostic ultrasound and magnetic resonance imaging has allowed rheumatologists to make treatment decisions that are based on objective data rather than ?gestalt.?

Analysis of epidemiologic information in the past has demonstrated that RA increases the likelihood of a patient having a myocardial infarction (heart attack).

It appears from recent preliminary data that the use of biologic drugs in combination with methotrexate has reduced the chance of this occurrence much more so than the use of conventional DMARD treatment by itself.

In addition, there have been significant reductions in the rate of hospitalization for pneumonia, and reduction in the incidence of flares of inflammatory eye disease due to RA.

Current biologic therapies are highly effective in treating RA, but alternatives are still needed for patients who have either primary non-response (not responding to the drug right out of the chute) or secondary non-response (losing effectiveness over time).

In addition to the first wave of biologic therapies which consist of drugs that block tumor necrosis factor (TNF), more recent biologic therapies such as rituximab (Rituxan) and abatacept (Orencia) may provide further benefits due to differences in mechanism of action.

These drugs are generally reserved for patients who have failed anti-TNF therapy.

A major hurdle that biologic drugs in general need to circumvent is the increased propensity towards infection, particularly tuberculosis with the anti-TNF drugs. In addition, an increased incidence of other fungal infections such as histoplasmosis and coccidiodomycosis has also been noted.

In addition, newer drugs in the anti-TNF class such as certoluzimab (Cimzia) and golimumab may also be welcome additions to the rheumatologists arsenal of weapons.

Cimzia appears to have a couple of attractive properties since it seems to have a rapid onset of action and also cause less pain at the site of injection.

Another biologic, tociluzumab- a humanized antibody- that blocks interlekin-6, also has demonstrated effectiveness in patients who have failed to respond to anti-TNF therapy.

Denosumab, which is a drug that blocks a substance called RANK ligand inhibits bone destruction in patients with rheumatoid arthritis and may also be effective for treating osteoporosis.

Finally, a class of drugs, called ?small molecules?- oral agents that block protein kinases, have far-reaching effects on the immune system and have shown impressive effects in rheumatoid arthritis. They have the added advantage of being oral. Unfortunately, they may, because of their mode of action, also have undesirable side effects... so further investigation is ongoing.

Nathan Wei, MD FACP FACR is a nationally known board-certified rheumatologist. For more info: Arthritis Treatment and Tendonitis Treatment Tips