TNF-inhibitors have been the gold standard for inducing remission in patients with rheumatoid arthritis. But what if they don抰 work? This article provides information on alternatives.

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease that causes both destructive joint changes as well as damage to internal organs.

The advent of drugs that block tumor necrosis factor such as Enbrel, Humira, and Remicade, has revolutionized our approach to the disease. However, what happens if these drugs don抰 work?

A review by M Asif A Siddiqui in the May 15, 2007 issue of Current Opinion in Rheumatology had some useful information. I will summarize and explain the implications in this article.

In long-standing RA, rituximab (Rituxan)- a drug that depletes B lymphocytes-and abatacept (Orencia)- a drug that inhibits T- cell functioning- in combination with methotrexate provide effective alternative options to anti-TNF drugs in the treatment of signs and symptoms in patients with methotrexate-resistant disease.

Another new drug, tocilizumab (Actemra)- a drug that blocks interleukin-6- also appears to be effective in these patients.

Rituximab and abatacept, in combination with methotrexate, were also effective when therapy with anti-TNF agents had not produced an adequate response.

In addition, abatacept plus methotrexate has been shown to slow the x-ray progression of methotrexate-resistant disease. Rituximab plus methotrexate may also improve x-ray progression of long-standing RA that does not respond adequately to anti-TNF therapy.

However, there is no advantage in adding abatacept to ongoing anti-TNF therapy. In fact, there is an increase in infectious complications with the combination. Other combinations of biologics involving different mechanisms of action have not been explored.

In early, aggressive RA, only tocilizumab monotherapy (single drug) has been evaluated, and has shown effectiveness in reducing x-ray progression of RA in one study, but this needs to be confirmed in well designed trials.

The newer biologics appear to be well tolerated, with an acceptable tolerability profile. More studies with longer follow-up times are needed.

Based on the evidence, the safe and effective dosages of abatacept, rituximab, and tocilizumab appear to be 10 mg/kg, 500 and 1000mg, and 8 mg/kg, respectively. Rituximab may have an advantage in terms of its schedule, since a single course consisting of two infusions 2 weeks apart produces a beneficial effect that can be sustained for up to 1 year, and sometimes longer. However, the safety of repeat courses of rituximab needs to be assessed.

The newer biologics are a useful and very welcome addition to the therapeutic arsenal employed against RA.