Treating to a Target in Established Active Rheumatoid Arthritis Patients Receiving a Tumor Necrosis Factor Inhibitor: Results From a Real‐World Cluster‐Randomized Adalimumab Trial

Abstract

Objective. In early rheumatoid arthritis (RA), treating to a target is more effective than routine care (RC). Our aim was to determine if treating to a target has better outcomes than RC in established active RA. Methods. We used a real-world, 18-month cluster-randomized trial in established active RA patients treated with adalimumab. Physicians were randomized to RC, treating to a Disease Activity Score in 28 joints (DAS28) of <2.6 (DAS group), or treating to a 0 of 28 swollen joint count (SJC; 0-SJC group). Results. Among the 308 enrolled patients, 109 (35.4%) were randomized to RC, 100 (32.5%) to the DAS group, and 99 (32.1%) to the 0-SJC group. When adjusting for baseline DAS28, a comparable but significant (P < 0.001) improvement in DAS28 was observed at 12 months for all groups (DAS28 mean score 3.1, 3.4, and 3.2, respectively). There were no significant between-group differences in the improvement of clinical parameters and patient-reported outcomes with the exception of the mean change in patient satisfaction over time (P ‫؍‬ 0.020), which was highest in the DAS group. Time to achieving good/moderate European League Against Rheumatism (EULAR) response was significantly shorter in the targeted treatment groups compared to RC (adjusted hazard ratio [HR] for the DAS-group 2.99 [95% confidence interval (95% CI) 1.71-5.24] and HR for the 0-SJC group 1.86 [95% CI 1.09 -3.13]). The dropout rate was 52.3% in RC, 27% in the DAS group, and 22.2% in the 0-SJC group (P < 0.001). Conclusion. All groups experienced significant improvements at 18 months of treatment with adalimumab. Treating to target in established RA did not differ from RC in terms of therapeutic end point achievement for patients remaining on treatment. However, time to achieving good/moderate EULAR response was significantly shorter in the targeted treatment groups compared to RC and, importantly, the dropout rate was significantly lower with targeted treatment.

The clinical effectiveness and cost-effectiveness of treat-to-target strategies in rheumatoid arthritis: a systematic review and cost-effectiveness analysis

“…50,52,63 One cluster RCT was rated as being at high risk of bias for blinded outcome assessment, 63 whereas the other two cluster RCTs were rated as being at unclear risk for this domain. 50,52 All three cluster RCTs were rated as being at high risk of attrition bias (> 10% participants withdrawing). 50,52,63 A trial protocol was not available for two cluster RCTs that were rated as being at unclear risk of bias for selective reporting.…”

“…the TIght COntrol for RA (TICORA) trial 61 examined patients with a disease duration of < 5 years and van Hulst et al 63 reported including both newly diagnosed patients and those with established disease (and did not report on the findings for these patients separately at all)]. Six studies 50 52,53 the T-4 study 56,57 and the TEAR trial [58][59][60] ) and six studies 26- 54 and the TEAR trial [58][59][60] ). Two studies 9,35,36,67 made other comparisons which did not seem to fit with any of the above comparisons (i.e.…”

“…Most studies specified a RA diagnosis based on ACR 1987 or 2010 criteria; however, the STREAM trial 55 required patients to have 2-5 swollen joints (and did not require an ACR diagnosis), the TICORA trial 61 required a DAS44 of > 2.4 and RA diagnosis was not reported in the Optimisation of Adalimumab study, 52,53 Saunders et al 54 or van Hulst et al 63 Sample sizes ranged from 82 to 755 participants and study durations (randomised phase) ranged from 24 weeks to 3 years. Six trials took place in the Netherlands, 26- …”

“…BehandelStrategieën in Reumatoïde Artritis (BeSt), 26- 55 the TreaTing to Twin Targets (T-4) study, 56,57 the Treatment of Early Aggressive Rheumatoid arthritis (TEAR) trial [58][59][60] and the early rheumatoid arthritis treated with tocilizumab, methotrexate or their combination (U-Act-Early) trial 62 ], three trials 9,50,52,53 examined an established RA population [i.e. British Rheumatoid Outcome Study Group (BROSG) trial, 9 Fransen et al 50 and the Optimisation of Adalimumab study 52,53 ] and two trials 61,63 examined populations that include both patients with early RA and those with established RA [i.e. the TIght COntrol for RA (TICORA) trial 61 examined patients with a disease duration of < 5 years and van Hulst et al 63 reported including both newly diagnosed patients and those with established disease (and did not report on the findings for these patients separately at all)].…”

“…50,52,63 All three cluster RCTs were rated as being at high risk of bias for blinding of participants and personnel. 50,52,63 One cluster RCT was rated as being at high risk of bias for blinded outcome assessment, 63 whereas the other two cluster RCTs were rated as being at unclear risk for this domain. 50,52 All three cluster RCTs were rated as being at high risk of attrition bias (> 10% participants withdrawing).…”