RA Treatment Strategies
Abstract 1309: Does Addition of Infliximab to Triple DMARD Plus Prednisolone Therapy Increase Rate of Remissions in Patients with Early Active Rheumatoid Arthritis? A Randomized Double-Blind Placebo-Controlled Study
The Fin-RACo trial, originally published in 1999, established that a regimen of “triple therapy” (methotrexate, sulfasalazine, and hydroxychloroquine) with or without low dose corticosteroid was superior to sulfasalazine monotherapy with or without low dose corticosteroid in achieving remission, slowing radiographic progression, and preventing work disability in RA patients with early disease (RA duration less than 2 years). The trial was conducted before the era of TNF inhibitors. Here, the Fin-RACo investigators present data from the “Neo-RACo” trial, exploring RA remission rates in subjects receiving combination therapy with triple therapy, infliximab, and low dose corticosteroids compared to those receiving triple therapy and low dose corticosteroids alone.
Methods This was a multicenter, randomized, double-blind, placebo controlled trial conducted at 15 centers in Finland. Subjects with active, DMARD-naïve RA of up to 12 months duration were randomized to receive infliximab 3 mg/kg or placebo infusion. All subjects received triple therapy (escalated to maximum tolerated doses of the components), prednisone 7.5 mg per day (tapered to off after 2 years), and intra-articular corticosteroid injection of affected joints. The proportion of subjects in remission at 6 and 12 months was compared between the groups, with ARA 1982 remission criteria utilized (no swollen or tender joints).
Results 99 subjects were randomized. Two-thirds of subjects were female with a mean age of 46 years. RA duration was 4 months from initiation of symptoms. Rheumatoid factor was present in 68% of subjects. Baseline disease activity was moderate to high, with an average of 20 tender and 16 swollen joints at entry.
Remission outcomes at 6 and 12 months
|
Triple therapy + Infliximab + Prednisone |
Triple therapy + Placebo infusion + Prednisone |
p | |
| Proportion in remission at 6 months | 58% | 47% | ns |
| Proportion in remission at 12 months | 58% | 45% | ns |
| Sustained remission (remission at both 6 and 12 mo) | 44% | 35% | ns |
| Mean ACR-N at 6 months | 96 | 91 | ns |
| Mean ACR-N at 12 months | 97 | 92 | ns |
Conclusions The addition of infliximab to an aggressively titrated regimen of triple therapy and low dose corticosteroid was not superior to the non-biologic combination regimen alone in achieving early sustained remission in DMARD naïve patients with early active RA.
Editorial Comment With the advent of multiple highly effective RA pharmacotherapies with established efficacy in early disease, combined with studies that have definitively shown the benefit of early combination DMARDs, a question that requires answering is “how much is too much?”. This study is novel in that it is the first to investigate an initial combination regimen of biologic DMARD + triple therapy.
These are preliminary results, in that the predefined outcomes were set at 2 and 5 years. Regardless, the results indicate that the addition of infliximab provides little additional benefit in the type of patients studied. However, it could be argued that the study is underpowered to show differences that may be clinically significant, as a 9% difference in the two groups in sustained remission is a difference that seems meaningful. Final conclusions on the propriety of triple therapy + biologic DMARD combination induction regimens must await the data for the primary outcome intervals, as well as data on radiographic outcomes, cost, disability, and safety as they emerge over the next years. It should be noted that the definition of remission utilized, no swollen or tender joints, is more stringent than the EULAR remission criteria often used in clinical trials, and more appropriate for the way that most practicing rheumatologists view remission status in their patients.
