Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): A randomized, controlled trial

Abstract

Objective. Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients.Methods. In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of <2.4).Results. Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P ‫؍‬ 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups.Conclusion. In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.Over the last 2 decades, the treatment of patients with rheumatoid arthritis (RA) has changed considerably. Currently, the goal of therapy is not only symptom

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

“…Our analysis showed that the effect of a TNF inhibitor plus methotrexate was significantly superior to combination DMARD treatment during the first 6 months, but this difference almost disappeared after 12 months, and especially after 18/24 months (no outcomes differed). Furthermore, in 3 studies using an initial course of steroids (3,4,14,15), there was no difference between the 2 treatment principles at any time (Figures 2-5 and Supplementary Figures 1-3, available in the online version of this article at http://onlinelibrary.wiley. com/doi/10.1002/acr.22618/abstract).…”

“…A recent indirect comparison network meta-analysis indicated that the effects of combination treatments with and without biologic agents might have similar properties to reduce radiographic joint destruction (2). Until recently, only 1 randomized controlled trial (RCT) directly supported this hypothesis (3,4). The 4 most sold drugs in the world with regard to sales (but not defined daily doses) are biologic agents primarily indicated for RA (adalimumab, infliximab, rituximab, and etanercept).…”

“…All analyses showed heterogeneity at 6 months, but few at 12 and 24 months. At 6 months, heterogeneity disappeared after the elimination of studies or treatment arms not using GC (3,11,12,16), which resulted in nonsignificant differences between a TNF inhibitor plus methotrexate and combination DMARD treatment (Figures 4 and 5, and Supplementary Figures 1 and 2), with the exception of radiographic progression ( Figure 3) and ACR70 response, (Supplementary Figure 3).…”

Continued Participation in a Ten‐Year Tight Control Treat‐to‐Target Study in Rheumatoid Arthritis: Why Keep Patients Doing their Best?

“…The BeSt Study was a multicenter, randomized, single-blind clinical trial (Dutch trial registry; trial numbers NTR262 and NTR265) set up to evaluate 4 dynamic treatment strategies in 508 patients with recentonset active RA (1987 American College of Rheumatology classification criteria) (9). Details of the study have been previously described (10). All patients gave written informed consent for the original study, and after separate approval from the medical ethics committees of the participating centers, also gave written informed consent for the additional questionnaire concerning the present topic.…”

My Treatment Approach to Rheumatoid Arthritis

“…57 This conclusion is supported by a 2010 Cochrane systematic review that emphasized lack of evidence of a statistically significant advantage for initial combination therapy using MTX and other conventional DMARDs over monotherapy with MTX. 58 A [59][60][61][62][63][64] The results of these studies suggest that the combination of MTX with a TNF inhibitor or CTLA-4:Ig (abatacept) has greater efficacy than MTX monotherapy insofar as both clinical and radiographic outcomes are concerned.…”