When it Comes to Treatment, Early is Best
by Denise Mann and Donna Rae Siegfried
Arthritis Today, June 2005

Receiving RA treatment sooner rather than later may be your key to remission.

A hot topic among rheumatologists lately is whether when you treat rheumatoid arthritis (RA) matters as much as how you treat it. Some believe strongly in the benefits of early treatment, prescribing an aggressive regimen of RA drugs during what is called "the window of opportunity." Doing so, they maintain, just may stop the disease in its tracks.

"I am a strong believer in the window of opportunity, which probably spans two years after symptom onset," says Salahuddin Kazi, MD, associate professor of internal medicine and chief of rheumatology at the Dallas VA Medical Center. "If RA goes untreated for two years, the majority of people with RA will develop joint erosion, indicating disease progression."

"The debate over whether a window of opportunity exists is semantics to some extent," says Arthur Kavanaugh, MD, rheumatologist and director of the Center for Innovative Therapy at the University of California, San Diego. "Some people don't like the term because people with active disease can -- and should -- always be treated, even beyond the two-year mark."

Treating RA as early as possible is not a new concept. In 1989, a study published in The Lancet emphasized the importance of starting a regimen of antirheumatic drugs early. The drugs commonly used then were hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine); methotrexate wasn't yet an option, and biologics were not yet developed. The main difference between discussions of early treatment 15 to 20 years ago and today are the drugs available for aggressive treatment, says Dr. Kavanaugh.

Early, aggressive treatment is particularly important for those who will develop a more serious disease. Figuring out who those patients are is quite a challenge, but there are some guiding principles. "I think it's pretty clear right now that if a patient has antibodies to rheumatoid factor (RF) or cyclic citrullinated proteins (anti-CCP) at any time during the course of disease -- from day one to 12 weeks or 12 years -- then he has a greater risk for persistent disease that is worse and more destructive," says Stephen Paget, MD, rheumatologist and physician-in-chief of the Hospital for Special Surgery in New York City. "Those patients need aggressive therapy that's constantly monitored."

A recent study of adalimumab (Humira) plus methotrexate showed one in two people with early RA -- diagnosed less than three years earlier -- achieved a clinical remission at two years. More than 60 percent of the patients showed at least a 50-percent improvement in symptoms. The effect with combination therapy was observed as early as two weeks, and these differences were sustained throughout the two-year study.

Another study, the Definitive Intervention in New-Onset Rheumatoid Arthritis (DINORA) trial, is reviewing the use of infliximab (Remicade) in people with very early inflammatory RA (those who had it fewer than 14 weeks) to see if it can prevent the development of destructive disease.

While it's ideal to initiate treatment as early as possible, aggressive treatment throughout the course of the disease is essential, say the experts.

"If you're past that two-year mark with no treatment or treatment that wasn't aggressive enough, all is not lost," says Dr. Kavanaugh.