TAMPERE, Finland—Eleven-year follow-up data show that starting treatment of early rheumatoid arthritis (RA) with a combination of 3 DMARDs produces better long-term results than starting with a single DMARD, even if patients in the monotherapy group switch to combination DMARDs after year 2 of treatment. According to Vappu Rantalaiho, MD, and colleagues from the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) Trial, the key is to have remission as the goal and to adjust therapy to maintain tight clinical controls, including use of intraarticular glucocorticoid injections. The data are reported in Arthritis & Rheumatism.1

3 conventional DMARDS seen as effective—and cheap

"We emphasize that after 11 years of RA, half of our patients had no disability according to the HAQ score, a finding that is in notable contrast with previously described cohorts."—Vappu Rantalaiho, MD
”[I]t is difficult to see why rheumatologists and RA patients should settle for single-DMARD therapy, when by starting with a combination of DMARDs, superior results are achieved without an increase in the number of adverse events. The combination of methotrexate, sulfasalazine, and hydroxychloroquine along with low-dose prednisolone, however, is not the ultimate, perfect treatment of early RA, since it does not cure the disease or produce sustained remission in all patients. Still, in real life, this combination is satisfactory for most patients and, even more importantly, is economically available for a large number of patients worldwide,” Dr. Rantalaiho said.

The researchers' economic considerations reflect widespread concern over the cost of and restriction of access to more expensive biologicals such as the TNF-α inhibitors in some countries with national health plans.

RA remission is the goal

The FIN-RACo study is the first published controlled trial using RA remission as the primary outcome target. The researchers randomized a cohort of 199 patients with early active RA to treatment with a combination of methotrexate, sulfasalazine, and hydroxychloroquine with prednisolone, or to treatment with a single DMARD with or without prednisolone. The researchers began with sulfasalazine for the single-DMARD arm, but switched to methotrexate as that drug came into wider use. After two years of treatment according to initial assignment, the treatment strategy became unrestricted, with remission remaining as the treatment goal.

Table 1. ACR Remission Rates After Combination vs. Single-DMARD Initial Treatment in Early RA*
Years after beginning treatment Combination DMARDS - ACR remission rates Single DMARD - ACR remission rates P
11 years 37.00% 19.00% 0.017
2, 5, and 11 years 13.00% 3.00% 0.006
1-2 of these time points 54.00% 37.00% 0.006
no time points 32.00% 60.00% 0.006
*Treatment regimen could be changed at physician's option after year 2.
Source: Adapted from Rantalaiho et al.1

The 11-year analysis included 68 patients in the combination-DMARD group and 70 in the single-DMARD group.

Mean HAQ scores improved significantly in both groups, probably reflecting the tight control, the researchers said.

“Targeting remission with tight clinical controls results in good functional and clinical outcomes in most RA patients,” the investigators concluded.

Almost two-thirds of patients in the combination-DMARD group achieved modified minimal Disease Activity (MDA), vs. 43% in the single-DMARD group.

ACR remission rates at 11 years were 37% in the combination-DMARD group and 19% in the single-DMARD group. [Table 1]

The investigators reported that in patients with clinically active early RA, initial treatment with a combination of traditional DMARDs produced better long-term clinical disease activity and remission than initial therapy with a single DMARD.

“Furthermore,” Dr. Rantalaiho wrote, “tight clinical control with adjustments in the active DMARDs and injections of intraarticular corticosteroids preserves function in most of these patients irrespective of the initial DMARD strategy....We emphasize that after 11 years of RA, half of our patients had no disability according to the HAQ score, a finding that is in notable contrast with previously described cohorts.”

Reference
1. Rantalaiho V, Korpela M, Hannonen P, et al. The good initial response to therapy with a combination of traditional disease-modifying antirheumatic drugs is sustained over time. The eleven-year results of the Finnish Rheumatoid Arthritis combination Therapy Trial. Arthritis Rheum. 2009;60:1222-1231.