Table 2.
Overview of studies based on clinical trials with relevance to treat-to-target adherence among physicians.
| Reference | Design | Characteristics | Population (n) | Follow-Up | Study Aim (s) | Outcome (s) | Key Findings | Commentary |
|---|---|---|---|---|---|---|---|---|
| Harrold et al., 2018, Arthritis Care Res [25] | cluster randomized multicenter controlled trial [NCT01407419] |
Pts eligible for treatment “acceleration” as assessed by rheumatologist, no criteria for prior medication use or disease duration, moderate to severe RA (CDAI > 10) in standard care |
532 | every 3 m (total 12 m) | Feasibility and efficacy of T2T vs. usual care | (i) rate of treatment acceleration conditional on CDAI >10 (ii) LDA; CDAI ≤10 achievement |
(i) T2T, 47% vs. UC, 50%; OR [95% CI], 0.92 [0.64–1.34]) (ii) LDA achievement T2T, 57% vs. UC, 55%; OR [95% CI], 1.05 [0.60–1.84] |
questionnaire-based, intention-to-treat analysis (ii), T2T physicians received prior training, while UC were aware of study aim, outcome assessed on patient level |
| Yu et al., 2017 Arthritis Care Res [39] | cluster randomized multicenter TRACTION controlled trial [NCT02260778] |
early to longstanding RA in standard care | 641 | 4 m for baseline and 4 m for intervention, total 9 m | Adherence to T2T in practice via screening of medical data | (i) specified disease activity target (ii) disease activity record with composite indices (iii) documented shared decision-making (iv) justified treatment decision |
(i–v) 64% of visits with no T2T element, 33% with 1, 2% with 2, 0.3% with all (ii) 25% of visits (iii) 39% of visits (iv) 0.3% of visits |
data extraction from electronic database of visits, intra- and inter-rater kappa ≥90, external assessors (not self-report) from study staff, outcome not on clinical level but as process-measure (visit level) |
| Solomon et al., 2017, Arthritis Rheumatol [40] | Impact of learning collaborative on T2T implementation | (i) change in composite T2T score [primary] (ii) positive change in implementation score (% pts) (iii) full implementation of all T2T items (% pts) |
(i) baseline for both arms (11%), after 9 months intervention, 57% vs. control, 25% (ii) 84% of pts in intervention arm vs. 37% in control (iii) in follow-up 26% in intervention arm and 6% in control |
randomization at site level, unblinded, sample size calculations may not be optimal, primary outcome was not validated previously, little data for baseline disease activity | ||||
| Kuusaulo et al., 2015, Scan J Rheumatol [22] | randomized, double-blinded, multicenter NEO-RACo controlled trial [NCT0090808] | early, active RA, DMARDs naïve | 99 | total 60 m (24 m for adherence) | Physician adherence to treatment protocol (CIS score) and clinical outcomes | (i) NEO-RACo remission (ii)DAS28 (iii) radiological joint changes (iv) cumulative work leave (v) DMARD use in y 2–5 |
(i) 3 m; lower CIS in pts with remission, 0.77 (0.62) vs. w/o 1.46 (0.74), at 2 y 1.83 (1.26) and 3.29 (2.61), respectively (ii) in 2–5 y, higher adherence associated with lower DAS28 than in other groups (iii) no impact on radiological progression (iv) no impact on work leave (v) good vs. low adherence; fewer DMARDs (and bDMARDs) |
retrospective analysis, internal consistency for scoring system 0.58 (0.40–0.76), majority of CIS from lack of i.a. GCs, physicians divided into tertiles by adherence, outcome analysis on patient level |
| Markusse et al., 2016, Arthritis Care & Res [36] | multicenter, randomized, controlled BeSt trial |
early, active RA, DMARDs naïve | 508 | 120 m | Evaluation of adherence to DAS-steered T2T strategy in RA with regard to associated conditions | Questionnaire response and T2T adherence; (i) protocol adherence agreement with DAS (ii) and protocol (iii) and RA suppression (iv) |
(i) Average 79% in 10-y (100 to 60% at end) (ii) ~80–90% of pts per visit (iii–iv) satisfied with treatment and RA suppression in 75–90% and 85–90% of visits |
treatment protocol designed by participating physicians, potential learning curve, and inclusion of younger rheumatologists more accustomed to “T2T”, questionnaire based, some analysis based on hypothetical conditions |
(i) Abbreviations: Usual care (UC), treat-to-target (T2T), odds ratio (OR), confidence interval (CI), month (m), year (y), disease modifying antirheumatic drug (DMARD), biologic (b), glucocorticoids (GCs), rheumatoid arthritis (RA), disease activity score (DAS), Low Disease Activity (LDA), Clinical Disease Activity Index (CDAI), new Finnish RA Combination Therapy (NEO-RACo), Behandel Strategieen (BeSt), treat-to-target in RA: Collaboration to Improve adoption and adherence (TRACTION). (ii) Cumulative Inactivity Scale (CIS) is a measure of adherence (lower score, higher adherence, maximum nonadherence of 15).