DMARDs Combo Cuts Time to First Remission in RA Save

A three-therapy protocol did not prove superior for achieving remission in rheumatoid arthritis (RA) patients after 1 year, but the regimen did lead to a shorter time until first remission versus a step-up approach, according to an analysis of the DREAM registry.

The treat-to-target (T2T) combination of disease-modifying antirheumatic drugs (DMARDs) consisted of high-dose methotrexate, hydroxychloroquine, and an optional intramuscular triamcinolone acetonide injection at the discretion of the rheumatologist. Remission was defined by a disease activity score28<2.6 (DAS28).

After 12 months of follow-up, remission was achieved at least once in 77.3% of patients in the treat-to-target combination group compared with 71.9% for those in the methotrexate monotherapy group (P=0.31), reported Laura Steunebrink, a PhD candidate at University of Twente in Enschede, the Netherlands, and colleagues.

However, the median time until patients achieved their first remission was 17 weeks (95% CI 13.2-20.8) in the combination group compared to 27 weeks (95% CI 20.7-33.3) in the methotrexate monotherapy group (P=0.04), they reported in Arthritis Research & Therapy.

At 6 months, more patients in the same combination group had also achieved remission at 61.7% compared with 45.9% for those in the monotherapy group (P=0.01) although this difference was no longer significant at month 12, the authors noted.

"Previous studies have shown that a shorter time until remission is related to the sustainability of remission, supporting the importance of early intervention with effective therapy to achieve early remission," they observed. "T2T using initial combination therapy may not be superior in the number of patients achieving remission in the longer term, but the strategy does lead to a significantly shorter time until first remission is achieved."

Treat-to-target, in which methotrexate (MTX) was initiated as monotherapy (15 mg/week), was implemented in the first Dutch Rheumatoid Arthritis Monitoring (DREAM) registry remission induction cohort in 2006. In the event of insufficient response, the methotrexate dosage was increased to 25 mg/week after 2 months. After 3 months, sulfasalazine (2,000 mg/day) was added. After 20 weeks, the sulfasalazine dose was increased (3,000 mg/day).

However, "a relevant proportion of patients still did not reach clinical remission within 12 months of treatment," the authors explained.

This led to the inception of a second cohort in 2012, whose patients received a the combination of DMARDs therapy -- an initial 20-mg/week dose of methotrexate and hydroxychloroquine at 200 mg twice daily. After 1 month, the methotrexate dose was increased to 25 mg/week, independent of disease activity. Only about half of the combination group at 53.3% received an intramuscular injection with triamcinolone at baseline.

In both cohorts, the patient populations consisted of adults with a clinical diagnosis of RA, and a disease duration (time from the diagnosis to the start of therapy) of less than 1 year. They were were enrolled consecutively immediately after a clinical diagnosis of RA.

The protocols assigned to each group were complex and based on DAS28 response at specific time points but as investigators underscored, "the vast majority" of both groups of patients were receiving only conventional synthetic DMARDs at 12 months.

Data were available on 121 patients in each group at study endpoint.

"Receiving an injection with triamcinolone ...was associated with a higher odds ratio (OR 2.14, 95% CI 1.03-4.46; P=0.04) of achieving first remission within 6 months but no longer with achieving remission within 12 months," Steunebrink's group noted.

The mean DAS28 in the combination cohort was also below the cutpoint for remission at 6 months compared with the mean DAS28 score for the monotherapy group, which remained above the remission cutpoint at month 6.

At 12 months, the mean DAS28 was <2.6 in both groups.

"Differences in disease activity and in time until remission are clinically important and are likely to also have significant social and economic impact," the authors observed, adding that patients who continue to have active RA are more prone to discontinue treatment than those whose disease is better controlled.

"The present study shows that both DREAM registry remission induction cohorts ... resulted in comparably high proportions of patients achieving remission within 12 months," they stated. "Optimal use of MTX in combination with other DMARDs early in the course of the disease leads to considerable improvement in disease activity."

Study limitations included the fact that it was "a quasiexperimental study" of two cohorts separated over time, the authors pointed out.

They also noted that because they used real-life observational data, "the results are generalizable to daily clinical practice," but they cautioned that longer follow-up was necessarily to evaluate the sustainability of remission in the second cohort.

Steunebrink and co-authors disclosed no relevant relationships with industry. 

This article is brought to RheumNow by our friends at MedPage Today. It was originally published March 21, 2016.