Efficacy and safety of treat-to-target strategy studies in rheumatic diseases: a systematic review and meta-analysis

The concept of treat-to-target (T2T), a treatment strategy in which treatment is directed to reach and maintain a defined goal such as remission or low disease activity (LDA), has been explored for several diseases including rheumatic diseases such as rheumatoid arthritis (RA). However, a comprehensive review of T2T in all rheumatic diseases has not recently been undertaken. To perform a systematic review and meta-analysis of the efficacy and safety of a T2T strategy in the management of adult patients with inflammatory rheumatic diseases. PUBMED, EMBASE and CINAHL were searched from January 1990 to December 2023 using key words related to a T2T strategy and rheumatic diseases; T2T strategy clinical trials or observational studies were included. Clinical, physical function and radiologic outcomes, cost-effectiveness, and adverse events (AEs) of the T2T strategies were investigated and a random-effect meta-analysis was conducted for the most commonly used outcomes in RA studies. The search identified 7896 studies, of which 66 fit inclusion criteria, including 50 in RA, 3 in psoriatic arthritis (PsA), 1 in spondyloarthritis (SpA) and 12 in gout. For the studies comparing a T2T strategy with usual care (UC) in RA, 83.3% (20/24) showed a T2T strategy could achieve significantly better clinical outcomes, and the meta-analysis showed that patients treated with a T2T strategy were more likely to be in remission (pooled RR: 1.68 (1.47-1.92), p<0.001] and achieve DAS-28 response (pooled standardised mean difference (SMD): 0.47 (0.26-0.69), P<0.001] at 1 year than patients treated with UC. Sensitivity analyses showed that a T2T strategy with a predefined treatment protocol had better clinical efficacy than that without protocol. In terms of improving physical function and health-related quality of life (HRQoL), 11/19 (57.9%) studies found a T2T strategy was significantly more likely to achieve these than UC, with the meta-analysis for the mean change of HAQ score supporting this conclusion (pooled SMD: 1.48 (0.46-2.51), p=0.004). Five out of 9 studies (55.6%) demonstrated greater benefit regarding radiographic progression from a T2T strategy. In terms of cost-effectiveness and AEs, 2/2 studies found a T2T strategy was more cost-effective than UC and 8/8 studies showed no tendency for AEs to occur more often with a T2T strategy. For the studies in PsA and SpA, a T2T strategy was also demonstrated to be more effective than UC in clinical and functional benefits, but not in radiologic outcomes. All gout studies showed that sUA level could be controlled more effectively with a T2T strategy, and 2 studies revealed that the T2T strategy could inhibit erosion development or crystal deposition. For patients with active RA, a T2T strategy has been shown in mulitple studies to increase the likelihood of achieving clinical response and improving HRQoL without increasing economic costs and AEs. Limited studies have shown clinical and functional benefits from T2T strategies in active PsA and SpA. A T2T strategy has also been found to improve clinical and radiologic outcomes in gout. T2T trials in other rheumatic diseases are lacking.