To be eligible for the Früharthritis-Ambulanzen, patient symptoms should not exceed three months, “since this time frame appears to constitute a window of opportunity,” he says. “Obviously we also see patients with longer-term early arthritis, but these go the more regular path.”
Another challenge, adds Dr. Smolen, “is the lack of diagnostic or classification criteria” for early RA, a topic he and coauthors addressed in an Arthritis & Rheumatism article, in which they discussed the need for and controversy surrounding criteria for early RA.5
At the 2006 ACR Annual Scientific Meeting, the Leiden EAC group presented their suggested criteria, which they prefer to call “a prediction rule.” Based on their study of 1,700 RA patients with recent-onset disease, they say the prediction rule for persistent RA should include nine clinical variables: gender, age, localization of symptoms, morning stiffness, tender and swollen joint count, C-reactive protein, rheumatoid factor, and anti-CCP antibodies.
Future Options
During the past 10 years, the Austrian group has learned that about 10% of patients with less than three months’ symptom duration already have erosions, “indicating that there may be a period of asymptomatic but already aggressive pre-arthritis,” says Dr. Smolen. Studies by his group have shown significant differences in all aspects of improvement with earlier treatment, but early DMARD therapy alone “is not sufficient in most patients to halt progression of the disease,” he says.
Among the newest medications in the RA treatment armamentarium, the biologic response modifiers can reduce inflammation and structural damage. Three of these drugs work by blocking the activity of tumor necrosis factor (TNF)–alpha molecules, while another works by blocking interleukin-1. However, since more than 40% of RA patients fare well on traditional DMARDs, in Europe biologics are not used until there has been an inadequate response to at least two conventional DMARDs.
On the other hand, the Behandel Strategieë (BeSt study)—including 508 Dutch patients with early RA and led by investigators from Leiden University—demonstrated that individuals treated very early with the DMARD metrotrexate plus the biologic infliximab experienced disease remission.6 Results of this study have also been published in Arthritis & Rheumatism7 and Annals of Internal Medicine.8
“It is likely that there will be a subgroup of patients with very early RA who will turn out to benefit from the very rapid introduction of anti-TNF therapy,” says Dr. Raza.
Dr. Smolen notes that, “if patients are still active after three months of traditional DMARD therapy plus steroids, we should consider adding a biological agent.”
