Over the past 10–15 years, several randomized controlled clinical trials have demonstrated that a TTT strategy can achieve superior clinical outcomes compared with usual care. Studies included to support evidence for TTT can be divided into randomized strategy trials, assessing the efficacy of treating to a specific target versus routine care in the comparator arm; and treatment target trials in which all treatment arms have a defined target, but different treatment strategies to reach the target are compared. All TTT trials have included relatively frequent assessment with recommendations for intensifying treatment when patients have not reached target. These trials (reviewed in Table 1) have been primarily conducted in Western Europe.(1–7, 10) The number of subjects included in TTT trials ranges from 96–508. Some of the trials required subjects in the TTT arm to be treated according to specific treatment algorithms and others allowed treating physicians to decide on treatments but required a specific disease activity goal. Almost all randomized at the subject level. Treating providers were not blinded to assignment group in most studies, but many of the trials employed blinded assessors. Duration of follow-up ranged from 6–36 months and few trials accounted for the clustering of subjects within practices.
The treatment targets varied across trials, and the rates of attaining the targets in the intervention arms ranged from 31–82%. The intervention arms’ rates of reaching target were enhanced compared to the control arms’ in all but one study. The safety of TTT was comparable to the non-TTT arms with no greater rate of withdrawal due to adverse events. Several noted reduced progression in radiographic measures, but not all. Almost no information is available regarding the cost of a TTT strategy.(11)
Data on the prognostic importance of consistent control of disease activity gave birth to the TTT strategy. Achieving optimal outcomes and aiming for targets using treatment strategies with maximum benefit and minimal harms was the biggest motivation for developing recommendations for treatment of RA.(12) A recent international task force issued recommendations about TTT. While these recommendations are not uniformly accepted, several aspects of these TTT recommendations and principles are important to highlight (see Table 2). Remission is specified as the primary target, but the recommendations note that low disease activity may be an appropriate alternative target. The ACR RA treatment guidelines also point out the importance of these treatment goals.(13) It is further noted that the choice of the disease activity measure and target may be influenced by comorbidities and drug toxicities, and that patients must be appropriately informed about the treatment target. Furthermore, the TTT recommendations embed several important principles, including that RA treatment should be based on a model of shared decision making. They also appropriately note that many aspects of TTT are based on limited evidence.