Early and Aggressive Combination Treatment May Result in Prolonged Remission of Rheumatoid Arthritis

Early and aggressive treatment with a combination of an anti-TNF therapy and a disease modifying antirheumatic drug could put rheumatoid arthritis into remission, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Some studies have shown that the early use of methotrexate and etanercept (Enbrel®) in combination can achieve clinical remission in people with RA, but it is unknown if this can be maintained after the patient stops taking etanercept.

Researchers followed 40 patients—whose average age was 50 and who had suffered from RA for an average of 6 months—to determine if the early and aggressive combination of both medications could place them into remission. Patients were randomly placed into two groups. The first group just received 20 mgs of methotrexate each week, while the second group received that in combination with 50 mgs of etanercept weekly, and both groups continued this treatment for 24 weeks. At 24 weeks, if a patient’s RA had gone into remission, he or she was then taken off etanercept.

To assess the success of the treatment, patients underwent full clinical examination, laboratory tests, X-rays, and functional evaluations at the beginning of the study and at weeks four, 12, 24, 28, 36 and 48. Researchers found that 85 percent of the patients taking the combination of both medications went into clinical remission at 24 weeks, while only 35 percent of those patients taking methotrexate alone achieved remission, and a greater percentage in the combination group achieved ACR 50 and 70 percent improvement (an established method of tracking improvement in RA patients) at 24 and 48 weeks. In addition, 60 percent of those initially taking the combination of both medications, who were treated with etanercept for 24 weeks, remained in remission up to week 48 – even after being taken off etanercept.

“In this small study, being treated at diagnosis with etanercept and methotrexate resulted in a greater number of patients going into remission than if treated with methotrexate alone,” explains Claire Sheehy, MB, MRCPI; Connolly Hospital, Blanchardstown, Dublin 15, Ireland.“There was also a greater number still in remission on methotrexate at one year if they had been treated for the first six months with combination therapy. This small scale study provides further evidence that priority should be given to trials of remission induction at diagnosis with biologic therapy with subsequent biologic withdrawal.”

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.

Editor’s Notes: Dr. Sheehy will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 9:30 – 9:45 AM on Wednesday, October 29, in Room 102.
Presentation Number: 2042

Remission Induction With Etanercept and Methotrexate In Very Early Rheumatoid Arthritis with Sustained Remission after Etanercept Withdrawal

Claire Sheehy, Eithne Murphy, Trevor Duffy, Maurice Barry. Connolly Hospital, Dublin, Ireland

Purpose: Aggressive treatment of early rheumatoid arthritis (RA) is based on the concept of a limited “window of opportunity”, early in the disease process, whereby higher remission rates and longer remission maintenance may be achieved. Studies have shown that early use of methotrexate (MTX) and etanercept (ETN) in combination can induce clinical remission but it is unknown if this can be maintained after withdrawal of ETN. This study was undertaken to compare rates of remission at 6 months in patients with very early RA treated with either MTX alone or with combination of MTX and ETN and to see if remission is then sustainable off etanercept.

Methods: Ethical approval was obtained. Treatment naïve patients with confirmed RA according to the American College of Rheumatology (ACR) criteria of between 6 weeks and 1 year duration were randomised to one of the 2 treatment groups. Group 1 received MTX only; group 2 was treated with MTX and ETN for 24 weeks and ETN was then withdrawn if the patient was in remission (defined as Disease Activity Score in 28 joints (DAS28)

<2.6 ). MTX was prescribed at a dose of 20mg weekly and ETN at the standard dose of 50mg weekly. Assessments including full metrologic evaluation, laboratory tests, radiographs, and functional evaluation using Health Assessment Questionnaire (HAQ) were performed at 0, 4, 12, 24, 28, 36 and 48 weeks.

Results: 20 patients were randomised to each group. There were no significant differences in baseline demographics between the 2 groups, with a mean age of 50, mean symptom duration of 6.3 months, mean HAQ 1.25 and mean DAS28 of 6.2. 60% had sero-positive RA. Results were analyzed using intention to treat statistics. 17 patients (85%) were in clinical remission in the combination group at 24 weeks while only 35% were in remission in the monotherapy group. A greater percentage of the combination group fulfilled ACR 50% and 70% improvement criteria at 24 and 48 weeks (see graph). 60% of those who had received ETN for 24 weeks remained in remission at 48 weeks on MTX alone; the corresponding figure for the MTX group was 30%.

Conclusions: Very early aggressive treatment with the combination of the anti TNF α agent etanercept and methotrexate results in significantly higher rates of clinical remission in early RA after six months (85% versus 35%). 60% of the original combination group and 70% of those who actually achieved remission after 6 months of combination therapy successfully remained in clinical remission on MTX alone, indicating that this strategy may be effective in very early disease.

Disclosure Block: C. Sheehy, Wyeth Pharmaceuticals, 2; E. Murphy, None; T. Duffy, None; M. Barry, None.

Source: American College of Rheumatology (ACR)