Early rheumatoid arthritis
16.04.2010 16:30
Prediction models for optimized diagnosis and therapy
Although it has been shown in various clinical studies that a rapid start of therapy can have a positive effect on the course of rheumatoid arthritis (RA) and improve the patient's chances of remission, treatment is usually carried out too late and the window of opportunity is therefore unused calmly.
This was the conclusion drawn by experts at a press conference supported by Wyeth Pharma – a Pfizer Group company – at the German Rheumatism Research Center (DRFZ) in Berlin. Especially at the beginning of the disease, a diagnosis based on common classification criteria is usually not possible because the clinical picture of RA only develops over time.
Therapeutic interventions must therefore be largely tailored to the expected course. As part of the CAPEA (Course And Prognosis of Early Arthritis) observational study currently started by the DRFZ, the prognostic significance of early signs of the disease for the long-term course is to be examined in order to gain insights into how arthritis patients should be optimally treated in the future at an early stage of the disease .
“For patients with early arthritis, a rapid start to therapy is crucial for the long-term progression of the disease,” explained Professor Dr. Matthias Schneider, Association of Regional Cooperative Rheumatism Centers (AGRZ), Berlin. Results of various randomized clinical trials with standardized therapy regimens have shown that patients with an early start to treatment and aggressive initial therapy, for example combination therapy, have a greater chance of achieving remission than patients with a later start to therapy or with initial monotherapy.
“Patients with rheumatoid arthritis who were treated with basic therapeutic drugs (DMARDs) quickly after the onset of symptoms had a significantly better outcome after two years than patients for whom therapy was only started about three months later,” explains Dipl.-Psych. Gisela Westhoff, German Rheumatism Research Center Berlin.
A current 2-year evaluation of the COMET study (Combination of Methotrexate and Etanercept in active early Rheumatoid Arthritis) showed that patients with rheumatoid arthritis benefit from early therapy with the TNF receptor etanercept (Enbrel) with simultaneous administration of methotrexate ( MTX) benefit. The aim of the COMET study was to compare the efficacy and tolerability of a combination of etanercept plus methotrexate with methotrexate monotherapy in patients with active early rheumatoid arthritis.
The results show that early continuous administration of combination therapy led to clinical remission, reduction of radiological progression and improvement of functionality significantly more often than monotherapy with methotrexate alone.
Window of opportunity often remains unused
“Nevertheless, many arthritis patients are only treated when the best chances of remission have already passed, i.e. the therapeutic window of opportunity has already closed,” says Schneider. Possible reasons are that inflammatory rheumatic diseases often present themselves with little clarity in the initial stages and the diagnostic criteria set by the American College of Rheumatology (ACR) are often not yet met at an early symptom stage.
“In view of this diagnostic challenge, it is recommended that the treatment of early arthritis be based primarily on the expected individual prognosis. However, there is currently a lack of suitable prediction models for this,” explained PD Dr. Marina Backhaus, Charité Berlin.
CAPEA - Course and prognosis of early arthritis
“It is still largely unclear how many patients with early arthritis can achieve remission under standard care conditions,” explained Westhoff. Findings on this are expected from the CAPEA study (Course And Prognosis of Early Arthritis) by the German Rheumatism Research Center in Berlin (DRFZ), which will start in April 2010.
The primary study aim of the two-year prospective observational study is to find out how many patients with early arthritis (= 6 months) achieve remission under the conditions of standard rheumatological care. Possible predictors of remission or chronicity of the disease are also evaluated. In addition to the established diagnostic measures, new procedures are also recorded and evaluated.
“This will create the largest early arthritis cohort ever recruited in Germany, which will include all currently available prognostic parameters,” says Westhoff. In two associated projects there is the possibility of examining biomarkers and carrying out power Doppler sonography in order to gain new prognostic insights.
More early rheumatology consultations needed
As part of a study previously carried out by the German Rheumatism Research Center (“referral project”), it was evaluated how long it takes from the onset of symptoms to the initial presentation to the rheumatologist and how many and which patients with rheumatoid arthritis reach the rheumatologist in the “window of opportunity”. Within three months, 17,908 patients admitted for the first time (average age 54 years, 72 percent women) were documented at 198 internal rheumatology facilities.
The probability of reaching the rheumatologist within three months of symptom onset depended solely on whether the facilities had appointments for patients with early arthritis within two weeks.
In facilities with a “fast track” for arthritis patients, 40 percent of patients were able to use the “window of opportunity”; For patients who had to wait longer than three months for their appointment, the figure was only 20 percent. “Early consultations with rheumatologists could probably shorten the time until the start of treatment more effectively than increased training for the referring physicians,” concludes Westhoff.
The previously common scheme of slowly escalating therapy for rheumatoid arthritis has been increasingly questioned in recent years. Clinical trial data indicate that starting treatment early improves the chances of remission. “With the help of the findings from the early arthritis cohort, we will be able to make an even more precise prediction of the course of the disease under standard care conditions in the future and thus support the initiation of rapid therapy tailored to the patient's individual prognosis,” concludes Professor Schneider.