Are Docs Adhering to Targeted Treatment in RA?

Bret Stetka, MD; Iris J.M. Markusse, MD


July 18, 2014

Editor's Note: While on site at the 2014 European League Against Rheumatism annual congress, held in Paris, France, June 11-14, 2014, Medscape spoke with Iris J.M. Markusse, MD, about her study looking at whether or not physicians are complying with the treat-to-target strategy used in the BeSt trial.[1]

Medscape: Can you give our readers some background on the BeSt study[2] as a basis for your work?

Dr. Markusse: The BeSt study (acronym for "behandel strategieën," the Dutch for "treatment strategies") is a randomized, multicentre, single-blinded clinical trial, which enrolled 508 patients with early, active rheumatoid arthritis (RA) between 2000 and 2002. Initially intended to last 2 years, the study was revised and extended to a follow-up period of 10 years. The main question was how the then-available medication could best be used, with primary endpoints of functional ability and radiographic damage progression.

Patients were randomly assigned to receive 1 of 4 dynamic treatment strategies: sequential monotherapy; step-up therapy (both starting with methotrexate monotherapy); initial combination therapy with methotrexate, sulfasalazine, and prednisone; or initial combination therapy with methotrexate and infliximab. If insufficient benefit was achieved, each treatment arm dictated subsequent treatment adjustments, increasing the dose or number of drugs, or switching to other medication, depending on the treatment arm and time in the study.

The treatment adjustments were based on the 3-monthly Disease Activity Score (DAS, based on a 44/53 joint count) measurements, aiming for a DAS ≤ 2.4. The study protocol dictated the following: When the DAS was > 2.4, the next treatment step was taken. If the DAS was ≤ 2.4 for at least 6 months, medication was tapered to a maintenance dose. Then, if the DAS was < 1.6 for another 6 months, medication was discontinued.

The BeSt study has previously shown that at group level, patients benefit most from initial combination therapy, which results in earlier clinical improvement, and less radiographic damage progression compared with initial monotherapy. However, after treatment adjustments each time clinical response was insufficient, the initial monotherapy arms catch up in clinical response at the end of year 1. In the following years, clinical response and functional ability remain stable over time, probably as a result of continued DAS targeted treatment.

Medscape: Building on the BeSt study, what were the objectives of the work you presented at EULAR?

Dr. Markusse: Initially -- mainly to let the participating rheumatologist express their opinion while still having the treatment protocol with which they may not always agree -- we included in the study a short questionnaire to be filled in by the treating physician at each 3-monthly visit. We used the answers to assess whether and why (or why not) the rheumatologists complied with the treat-to-target strategy in the BeSt trial. This is relevant, because various reports show that implementation of treating-to-target in daily practice is still a challenge.

Thus, the aim of our study was to determine whether the rheumatologists at 20 participating centers indeed followed this targeted treatment protocol, and to identify possible reasons for deviating from this protocol.

Every 3 months, the rheumatologists were asked to answer a few-multiple choice questions:

  • Do you agree with treatment according to the study protocol? (yes/no);

  • Do you agree with the DAS as a representative of actual disease activity? (yes/no, it underestimates actual disease activity/no, it overestimates disease activity); and

  • Are you satisfied with the level of disease suppression? (yes/no).


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.