Medical Research: What is the background for this study? What are the main findings?
Response: Rheumatoid Arthritis (RA) is a chronic systemic auto immune disease characterized by pain and swelling in the joints, mostly in arms and legs. Around 1% of the world population is affected by this hazardous disease. Left untreated this can lead in the short term to loss of quality of life and in the long term to major bone damage and immobility. Rheumatoid Arthritis can not be cured, but the disease can be suppressed.
International guidelines recommend to treat a patient with Rheumatoid Arthritis early, intensive and to target low disease activity, but leave much freedom in choice of medication and strategy. Our CareRA ( Care in early RA) research group, under the leadership of Prof Dr Verschueren and Prof Dr Westhovens tried to untangle long standing questions regarding the management of Rheumatoid Arthritis.
In this RCT, we want to question the benefit of a combination of disease modifying anti rheumatic drugs compared to monotherapy and the benefit of a high starting dose of glucocorticoids versus moderate dose. We choose glucocorticoid therapy over biological therapy because of its widespread use in RA and cost-effectiveness compared to the expensive biological therapy.
Therefore, 290 patients with the presence of poor prognostic markers (disease activity, erosions and serum markers RF/ACPA) were randomzied into 1 of 3 medication schemes:
1. Cobra Classic: methotrexate + sulphasalazine + 60mg glucocorticoid starting dose
2. Cobra Slim: methotrexate + 30mg glucocorticoid starting dose
3. Cobra Avant-Garde: methotrexate + leflunomide + 30 mg glucocorticoid starting dose
The glucocorticoid doses were tapered every week. After 6 or 7 weeks, they were on maintenance dosage and discontinued after 28 weeks.
All patients are followed in a tight control schedule ( a close follow-up scheme), aiming for low disease acitvity.
After 16 weeks, 7 out of 10 patients were in remission, a state where the disease is clinically suppressed. No differences in efficacy outcomes were observed between the three groups. However, the safety profile of the Cobra Slim group is much more favourable because only half of the number of adverse events were observed in this group compared to Classic and Avant-Garde.
Medical Research: What should clinicians and patients take away from your report?
Response: First of all, remission rates are internationally the highest reported after 16 weeks of Rheumatoid Arthritis treatment. Thus, our three intensive treatment schedules are all valuable in daily clinical practice to treat patients.
Secondly, the treatment schedules are much cheaper compared to biological therapy and have at least a comparable safety profile again compared to biological therapy. Thus, healthcare systems can save a lot while not sacrifycing any clinical efficacy.
Thirdly, our study shows that Methotrexate alone is comparable to combination therapy when combined with a bridging scheme of glucocorticoids. Hence, this results is good for patients struggling with the more and more emerging problem of polypharmacy.
Lastly, our results indicate that a moderate or high starting dose of glucocorticoids does not matter.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Our results should of course be confirmed after 1 and 2 year follow-up. Future research should focus on the period after initial intensive treatment. How can we help the 30% of patients who fail this therapy? Can we perhaps identify these patients and adapt therapy? These studies could perhaps show the way to individualized RA treatment. Our CareRA research group will continue to study these problems and we hope to deliver answers to these questions!
Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial.
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