Rheumatoid Arthritis Remission

Got RA? Remission may be reachable.

Posted 5/8/07

Putting RA into remission may not actually be as daunting as the death-defying tasks that brought super-spy Ethan Hunt out of retirement in Mission Impossible III. In fact, it may be well within the grasp of nearly half of the 2.1 million Americans with RA.

“If you have fewer than 15 minutes of morning stiffness and no tender or swollen joints for at least three months, that’s definitely remission,” says Salahuddin Kazi, the chief of rheumatology at the Dallas VA Medical Center in Texas. “From a functional perspective, you can do all that you want to do. You have no limitations and no pain.”

Sound too good to be true? It’s not, says Désirée van der Heijde, MD, a professor of rheumatology at the University Hospital Maastricht in the Netherlands. She says with today’s newer treatments, as well as with more aggressive use of older treatments, like methotrexate, nearly half of people with RA can – and should – achieve remission. In the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO), a two-year study of 682 people with RA from 92 treatment centers in Europe and Australia, more than three quarters of people treated with the biologic drug etanercept (Enbrel) plus the disease-modifying antirheumatic drug (DMARD) methotrexate experienced no progression of joint damage at three years. More than 40 percent achieved clinical remission.

Study Highlights

• Included were adults 18 years or older from 22 countries with adult-onset rheumatoid arthritis of at least 3 months but no longer than 2 years, DAS28 score of 3.2 or higher, and either a Westergren erythrocyte sedimentation rate of 28 mm/hour or higher or C-reactive protein of 20 mg/L or higher.
• 542 patients were randomized to receive either etanercept-methotrexate (n = 274) or methotrexate alone (n = 268).
• Etanercept was given as a subcutaneous injection at 50 mg (25 mg twice daily) per day for 52 weeks.
• Methotrexate was given orally starting at 7.5 mg once a week and increasing to 20 mg per week for 8 weeks in both groups.
• Folic acid supplementation at 5 mg twice weekly was given to reduce adverse effects of methotrexate.
• Stable doses of corticosteroids (≤ 10 mg per day of prednisone or equivalent) or a single nonsteroidal anti-inflammatory drug was permitted if started at least 4 weeks before baseline and was given at a constant dose in the first 24 weeks of the study.
• Radiographs of the hands, wrists, and feet were taken at baseline and at week 52.
• 221 (80.7%) in the combined and 189 (70.5%) in the methotrexate-only group completed the study.
• Primary endpoints were proportion achieving clinical remission defined as DAS28 score of less than 2.8 and change in modified total Sharp score for radiographic progression from baseline to 52 weeks.
• Modified total Sharp score measured joint erosion and joint space narrowing.
• Radiographs were reviewed by 2 physicians blinded to allocation.
• Other endpoints were change in functional status measured by the health assessment questionnaire disability index and an employment questionnaire asking if participants had stopped working since the last visit.
• Mean age was 50.5 to 52.3 years, three quarters were women, 88% were white, one fifth had used disease-modifying antirheumatic drugs, and half had used corticosteroids in the past.
• 87% were from Europe and Australia, and the remainder were from Latin America and Asia.
• 92% had a DAS28 score of more than 5.1, indicating severe disease.
• At 52 weeks, the proportion who achieved DAS28 remission (defined as a score < 2.6) was significantly greater in the combined (50%) vs the methotrexate group (28%) with an effect difference of 22.05% (P < .0001).
• This difference was seen as early as week 2 with significant reduction in swollen joints (85% improvement in the combined vs 65% improvement in the methotrexate group by 52 weeks).
• Normal health assessment questionnaire disability index was defined as 0.5 or less; 55% of the combined vs 39% of the methotrexate group achieved this endpoint, with an effect difference of 16.10% (P = .0004).
• Radiographic nonprogression was defined as a modified total Sharp score of 0.5 or less; 80% of those in the combined vs 59% in the methotrexate group (P < .0001) achieved this endpoint.
• Most of the radiographic benefits were achieved by a reduction in joint erosion rather than joint space narrowing in the combined group.
• The proportion achieving DAS44 remission was also greater in the combined vs the methotrexate group (effect difference, 9.07%) at all time points and at 52 weeks.
• 91.8% in the methotrexate and 90.2% in the combined group reported adverse effects, and serious adverse effects were similar in the 2 groups (12.7% in the methotrexate vs 12.0% in the combined group).
• The authors concluded that use of combined vs methotrexate therapy was associated with better clinical remission and arrest of radiographic progression in patients with early, active, moderate to severe rheumatoid arthritis.