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

Abstract

Objectives: A treat-to-target (T2T) strategy has been shown to be superior to usual care in rheumatoid arthritis (RA), but the optimal target remains unknown. Targets are based on a disease activity measure (eg, Disease Activity Score-28 (DAS28), Simplified Disease Activity Indices/Clinical Disease Activity Indices (SDAI/CDAI), and a cut-off such as remission or low disease activity (LDA). Our aim was to compare the effect of different targets on clinical and radiographic outcomes.

Methods: Cochrane, Embase and (pre)MEDLINE databases were searched (1 June 2022) for randomised controlled trials and cohort studies after 2003 that applied T2T in RA patients for ≥12 months. Data were extracted from individual T2T study arms; risk of bias was assessed with the Cochrane Collaboration tool. Using meta-regression, we evaluated the effect of the target used on clinical and radiographic outcomes, correcting for heterogeneity between and within studies.

Results: 115 treatment arms were used in the meta-regression analyses. Aiming for SDAI/CDAI-LDA was statistically superior to targeting DAS-LDA regarding DAS-remission and SDAI/CDAI/Boolean-remission outcomes over 1-3 years. Aiming for SDAI/CDAI-LDA was also significantly superior to DAS-remission regarding both SDAI/CDAI/Boolean-remission (over 1-3 years) and mean SDAI/CDAI (over 1 year). Targeting DAS-remission rather than DAS-LDA only improved the percentage of patients in DAS-remission, and only statistically significantly after 2-3 years of T2T. No differences were observed in Health Assessment Questionnaire and radiographic progression.

Conclusions: Targeting SDAI/CDAI-LDA, and to a lesser extent DAS-remission, may be superior to targeting DAS-LDA regarding several clinical outcomes. However, due to the risk of residual confounding and the lack of data on (over)treatment and safety, future studies should aim to directly and comprehensively compare targets.

Prospero registration number: CRD42021249015.

Keywords: arthritis, rheumatoid; outcome and process assessment, health care; outcome assessment, health care.

Figure 1

Flow chart of article selection. DMARD, disease-modifying antirheumatic drug.

Figure 2

Effect of the DAS28/44-remission and SDAI/CDAI-LDA treatment targets compared with the target of DAS28/44-LDA, on different outcomes and at different time points based on meta-regression analyses (parsimonious models). Results are presented in comparison to a treatment target of DAS-LDA. Exact coefficients and CIs can be found in online supplemental tables S2–S4. *The natural log of yearly SHS progression was used in the analysis. The models were corrected for the following covariates. Mean DAS28-ESR year 1: formal treatment, bDMARD, BL DAS28-ESR, years 2–3: mean RF/ACPA, early/established RA, BL DAS28-ESR. DAS remission year 1: remission type, bDMARD, early/established RA, BL DAS28-ESR, years 2–3: remission type, formal treatment, BL DAS28-ESR, years 4–6: remission type, symptom duration, BL DAS28-ESR. Mean SDAI/CDAI year 1: SDAI/CDAI, formal treatment, bDMARD, early/established RA, BL DAS28-ESR. SDAI/CDAI/Boolean remission year 1: remission type, formal treatment, early/established RA, BL DAS28-ESR, years 2–3: remission type, bDMARD, early/established, BL DAS28-ESR. SHS progression year 1: formal treatment, mean RF/ACPA, symptom duration, log(BL SHS), log(BL SHS)^∧2, years 2–3: mean RF/ACPA, log(BL SHS), log(BL SHS)^∧2. Mean HAQ year 1: bDMARD, early/established RA, BL HAQ, years 2–3: BL HAQ. ACPA, anticitrullinated protein antibody; bDMARD, biological disease-modifying antirheumatic drug; BL, baseline; CDAI, Clinical Disease Activity Index; DAS(28/44), Disease Activity Score (28/44 indicating the joint count); ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; LDA, low disease activity; RA, rheumatoid arthritis; REM, remission; RF, rheumatoid factor; SDAI, Simplified Disease Activity Index; SHS, Sharp van der Heijde Score; T2T, treat to target.