Chalking up a double-whammy

New research published in The Lancet shows that two is better than one when it comes to treating RA

By Owen Dyer

Agnes Brookes is 53 and suffers from rheumatoid arthritis (RA). She was diagnosed six years ago. When she feels that stiffness in her knees and hands, she usually reaches for the aspirin bottle, even though the drugs aren't working as well as they used to. New research now points to a drug-combo that could help ease Agnes's pain.

Etanercept, a genetically engineered protein that inhibits tumour necrosis factor, is a recent addition to the armoury of RA drugs, whereas rheumatologists have prescribed methotrexate for decades � its popularity rising and falling according to the promise of new alternative drugs. Measured head to head, the two drugs have proved about equally successful in controlling symptoms of the disease. Now, a new international study that looked at combining these two widely used RA drugs has provided the first evidence that bone damage caused by the disease could potentially be reversible.

The results of the study, published in the February 28 issue of The Lancet, enrolled patients from the US and several European countries in a double-blind, randomized study. Six hundred and eighty-six patients with active RA were randomly allocated to treatment with etanercept, oral methotrexate, or the combination.

The patients were measured by American College of Rheumatology (ACR) functional criteria and by Sharp score, a system for comparing radiographic results. Etanercept (25mg) was given subcutaneously twice a week, while oral methotrexate doses were up to 20mg every week.

ACR scores were better for symptom relief after six months for patients given combination treatment than for those receiving individual drug therapy. Remission after one year occurred in 35% of patients given combination treatment compared with 16% of patients given etanercept monotherapy and 13% given methotrexate monotherapy. Combination therapy was also more effective in slowing joint destruction measured by radiography, resulting in a statistically significant improvement on a score for joint erosion.

Among the monotherapy groups, patients on etanercept did better than those on methotrexate. The number of adverse events was roughly equal in all groups, including infections, which have been associated with etanercept in the past.

Lead author Dr Lars Klareskog from the Karolinska Institute, Sweden, said, "this is the first demonstration that erosions in established rheumatoid arthritis can improve over time in a group of patients within a controlled clinical trial, thus providing evidence that repair of joints destroyed by the disease may be a biological and clinical possibility."

As with most clinical research in rheumatology, this study made no attempt to recruit patients in the earliest stages of disease. Yet the majority of specialists are convinced that the greatest benefit from the newer drugs, and from methotrexate itself, will be seen in patients in the first few months of the disease.

In a commentary accompanying The Lancet article, Dr Armin Schnabel from Sana Rheumazen-trum Baden-Wrttemberg, Germany, argues that there's a window of opportunity, during which "inflammation seems to be particularly susceptible to treatment and long-term preservation of structure and function probably relies heavily on the initiation of effective immunosuppression during this particular time span."