The sustained benefits of very early treatment of rheumatoid arthritis with anti-TNF-alpha therapy

[Guest guest]

The sustained benefits of very early treatment of rheumatoid arthritis with

anti-TNF-alpha therapy

Promising new evidence for the optimal use of biologic therapies

A major cause of pain and disability, rheumatoid arthritis (RA) is also

potentially the most treatable form of chronic arthritis. Researchers,

doctors, and patients agree that a group of drugs called disease-modifying

antirheumatic drugs (DMARDs) can effectively reduce joint pain and

stiffness. Yet, even when prescribed early and aggressively, DMARDs alone do

not guarantee the desired outcome: the rapid and prolonged suppression of

inflammation needed to induce remission.

Fortunately, there is new hope for treating RA early and experiencing

long-lasting gains. Biologic agents that target tumor necrosis factor

(TNF)-alpha ­ a protein known for provoking inflammation ­ have been

successfully used to curtail the activity of rheumatoid arthritis among

other chronic inflammatory conditions. Recently, a team of researchers in

the United Kingdom set out to test the effectiveness of anti-TNF-alpha

therapy on a small sample of patients with very early, poor-prognosis,

previously untreated RA. The promising results and practical treatment

implications of their pilot study are featured in the January 2005 issue of

Arthritis & Rheumatism

(http://www.interscience.wiley.com/journal/arthritis).

Based at Leeds General Infirmary, the research team recruited twenty

patients with a diagnosis of RA meeting the American College of

Rheumatology's criteria. On average, the patients had complained of disease

symptoms for six months. None had ever been prescribed DMARDs or steroids.

At the study's onset, the patients were randomly divided into two treatment

groups. One group received a standard dosage of a TNF-alpha inhibitor,

infliximab (also known by the commercial name Remicade), while the other

group received the a placebo. Patients in both groups also began a course of

escalating DMARD therapy with methotrexate. DMARDs are drugs that improve

the signs and symptoms of RA and reduce damage as shown by joint X-rays

All twenty RA patients adhered to their assigned treatment for a full year.

To closely monitor the impact of anti-TFN-alpha therapy on synovitis, the

inflammation of the membrane lining the joints, as well as bone erosions,

every patient underwent magnetic resonance imaging (MRI) scans of the hand

at baseline, at four weeks, and then at eight-week intervals until 54 weeks.

The MRI scans were repeated a final time at 104 weeks ­ one year after the

patients stopped taking infliximab.

At its one-year culmination, the study achieved its primary goal for RA

patients given the advantage of early anti-TNF-alpha therapy: disease

remission to avert joint damage. At 14 weeks, according to the MRI findings,

patients taking infliximab combined with methotrexate showed a significant

reduction in levels of synovitis compared to their baseline scores and to

their counterparts. At 24 weeks, the infliximab group had significantly

fewer new telltale signs of joint erosions than the placebo group.

Throughout the course of the study, up to week 104, remission rates were

greater among those patients prescribed infliximab plus methotrexate. 7 out

of 10 of the patients had met the ACR response criteria for remission,

compared with 2 out of 10 patients in the placebo plus methotrexate group.

One year after withdrawing from anti-TNF-alpha therapy, the patients in this

group continued to experience therapeutic benefits. These patients scored

significantly higher on measures of function and quality of life than the

patients who had been treated with conventional DMARDs alone. " This appears

to emphasize the importance of not only adequate disease suppression over

time, but also of rapid disease suppression for optimal improvement in these

outcomes, " notes the study's author, Mark A. Quinn. " Rapid control of

disease activity may prevent patients from entering the 'sick role' and may

avoid the socioeconomic disadvantages associated with chronic illness, which

extend beyond the anti-inflammatory nature of the therapy. "

Despite the small sample of patients, this study has important implications

for the most effective, affordable, short-term use of anti-TNF-alpha

therapy, at the very early stages of RA. " Large-scale studies are under way

to confirm these findings, " Quinn reports.