Treat-to-Target Strategies in Rheumatoid Arthritis: a Systematic Review and Cost-Effectiveness Analysis

Abstract

To systematically review clinical and health economic impacts of treat-to-target (TTT) strategies in patients with rheumatoid arthritis (RA) managed in specialist units, compared with routine care. Sixteen and seven electronic databases were searched for clinical RCTs and cost-effectiveness respectively. Study selection, data extraction and quality assessment (Cochrane Collaboration risk of bias criteria) were performed. Evidence was reported by (1) TTT vs. usual care; (2) comparison of different treatment protocols against each other; (3) comparison of different targets against each other. Narrative synthesis was undertaken and conclusions drawn on a trial by trial basis, due to study heterogeneity. Twenty-two RCTs were included. Sixteen were at high risk of bias, five unclear and one low risk. Three trials showed TTT to be more effective than usual care in terms of remissions, in some or all comparisons, whereas one other trial reported no significant difference. Two trials showed TTT to be more effective than usual care in terms of low disease activity (LDA), in some or all comparisons, whereas two trials reported little difference. Some evidence suggests that TTT strategies involving combination therapy can achieve more remissions than those involving monotherapy, but little impact of alternative treatment targets on remission or LDA. Overall, there is evidence that TTT increases remissions in early RA and mixed early and established RA populations, and increases LDA in established RA. Although results varied, typically TTT was estimated to be more cost-effective than usual care. No target appears more effective than others.

Systematic Literature Review of the Use of Productivity Losses/Gains in Cost-Effectiveness Analyses of Immune-Mediated Disorders

“…Although our searches did not identify any SLRs that covered CEAs for a broad range of immune-mediated disorders, we did identify SLRs of CEAs for individual immune-mediated disorders with one study each for rheumatoid arthritis [ 37 ], inflammatory bowel disease [ 38 ], psoriatic arthritis [ 39 ], and psoriasis [ 40 ]. The review of rheumatoid arthritis CEAs [ 37 ] examined the cost-effectiveness of treat-to-target strategies, while the review of inflammatory bowel disease [ 38 ] examined therapeutic drug monitoring and did not mention productivity losses.…”

“…Although our searches did not identify any SLRs that covered CEAs for a broad range of immune-mediated disorders, we did identify SLRs of CEAs for individual immune-mediated disorders with one study each for rheumatoid arthritis [ 37 ], inflammatory bowel disease [ 38 ], psoriatic arthritis [ 39 ], and psoriasis [ 40 ]. The review of rheumatoid arthritis CEAs [ 37 ] examined the cost-effectiveness of treat-to-target strategies, while the review of inflammatory bowel disease [ 38 ] examined therapeutic drug monitoring and did not mention productivity losses. In the other two studies [ 39 , 40 ], the results included findings from previous studies that included productivity losses in CEA; here, the authors pointed out that including productivity losses in CEA would affect the results of the analysis, but they did not compare the results of CEAs that included productivity losses with those that did not.…”

What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis

“…Previous reviews have also considered the optimal target in a T2T strategy, although only narratively. 95 96 Hock et al report no preference for any particular target. Bergstra and Allaart conclude that based on the limited available and indirect evidence, aiming for remission rather than LDA (types not specified) seemed to result in more patients achieving remission, but not better physical functioning.…”

“…Previous reviews have also considered the optimal target in a T2T strategy, although only narratively 95 96. Hock et al report no preference for any particular target.…”

Treating Rheumatoid Arthritis in Zanzibar: a cost effectiveness study comparing conventional, biologic, and targeted-synthetic disease modifying anti-rheumatic drugs

“…The study looked at the cost-effectiveness of providing treatment in a stepwise approach, which simulates a clinical setting and is in accordance with recommendations in international clinical guidelines. We do believe that using a T2T approach which predefines treatment goals and applies tight control via regular, appropriate treatment adjustment (49) enables limitation of costs as it is more effective in reaching treatment target than usual care (50). All patients are started on the most cost-effective drug and the least cost-effective therapies are reserved for few and select patients.…”