Arthritis Care & Research Vol. 68, No. 4, April 2016, pp 446–453 DOI 10.1002/acr.22681 V C 2016, American College of Rheumatology ORIGINAL ARTICLE Evaluating Adherence to a Treat-to-Target Protocol in Recent-Onset Rheumatoid Arthritis: Reasons for Compliance and Hesitation I. M. MARKUSSE, 1 L. DIRVEN, 1 K. H. HAN, 2 H. K. RONDAY, 3 P. B. J. DE SONNAVILLE, 4 P. J. S. M. KERSTENS, 5 W. F. LEMS, 6 T. W. J. HUIZINGA, 1 AND C. F. ALLAART 1 Objective. To evaluate rheumatologists’ adherence to a low Disease Activity Score (DAS)–steered treat-to-target (T2T) strategy in treatment of patients with rheumatoid arthritis (RA) and to assess associated conditions. Methods. Data of the BeSt study were used, a multicenter T2T strategy trial with 10-year followup. During 3 monthly vis- its, the physician answered questions about satisfaction with level of RA suppression, agreement with the study protocol, and agreement with the DAS. Associations between the answers and nonadherence were evaluated. Results. Protocol adherence decreased over time from 100% to 60% per visit, with an average over time of 79%. Rheumatolo- gists mostly agreed with the DAS (80–90% of visits over time) and were satisfied with the treatment steps (75–90%) and with the level of RA suppression (85–90%). The odds for protocol violation were higher when the rheumatologist disagreed with the DAS (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 2.0–2.7 when they thought the DAS overestimated actual disease activity; OR 2.5, 95% CI 2.0–3.1 when they thought the DAS underestimated actual disease activity) or with the next required treatment step (OR 3.0, 95% CI 2.5–3.5), and when the physician was dissatisfied with disease suppression (OR 1.3, 95% CI 1.1–1.6). Conclusion. Rheumatologists generally agreed with and followed a 10-year followup DAS-steered T2T strategy. Dis- agreement with the DAS or the required treatment and dissatisfaction with the level of disease suppression were risk factors for nonadherence. These results indicate the feasibility of continued protocol-driven T2T therapy. For daily practice, adherence to T2T therapy might be improved by adopting the structure components of a clinical trial. INTRODUCTION Targeted treatment has proved to effectively suppress dis- ease activity in patients with early rheumatoid arthritis (RA) (1–4). These days, treat-to-target therapy is a well-known concept in trials (1,3–6), and is also recommended in daily practice (7–9). Questionnaire-based research showed that the majority of rheumatologists agreed with this recommen- dation (10). Other studies suggest that actual implementa- tion of a treat-to-target approach in daily practice remains challenging (11–14). One of the reasons may be that rheuma- tologists are reluctant to base treatment decisions on a com- posite score such as the Disease Activity Score (DAS) (15), arguing that it is too sensitive for noninflammatory pain (16) or may be falsely elevated when erythrocyte sedimentation rate (ESR) or C-reactive protein level is elevated due to non- rheumatic inflammation (17). In the BeSt study, treat-to-target therapy is a central theme of the initial study design, which is embedded in the daily practice of rheumatologists in 20 participating hospi- tals, and maintained over 10-year followup. In the current post hoc analysis, we set out to determine to what extent the rheumatologists adhered to the treat-to-target protocol and to identify factors influencing this adherence, such as satisfaction with the level of disease activity, agreement with the DAS, agreement with the next treatment step, and apparently contradictory DAS components. PATIENTS AND METHODS In the BeSt study (Dutch acronym for treatment strategies), a clinical trial with 2 academic and 18 peripheral participating Supported by Schering-Plough and Janssen, and by a grant from the Dutch Insurance Companies. 1 I. M. Markusse, MD, L. Dirven, MSc, PhD, T. W. J. Huizinga, MD, PhD, C. F. Allaart, MD, PhD: Leiden University Medical Center, Leiden, The Netherlands; 2 K. H. Han, MD: Maasstad Hospital, Rotterdam, The Netherlands; 3 H. K. Ronday, MD, PhD: Haga Hospital, The Hague, The Netherlands; 4 P. B. J. de Sonnaville, MD: Admiraal de Ruyter Hospital, Goes, The Netherlands; 5 P. J. S. M. Kerstens, MD, PhD: Reade Hospital, Amsterdam, The Netherlands; 6 W. F. Lems, MD, PhD: Reade Hospital and VU Medical Center, Amsterdam, The Netherlands. Dr. Lems has received speaking fees (less than $10,000) from Janssen. Dr. Huizinga has received speaking fees (less than $10,000) from Janssen. Dr. Allaart has received speak- ing fees (less than $10,000) from Janssen. Address correspondence to I. M. Markusse, MD, Leiden University Medical Center, Department of Rheumatology, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail: i.m. markusse@lumc.nl. Submitted for publication February 17, 2015; accepted in revised form July 21, 2015. 446