Background/Purpose : In a treat-to-target strategy in rheumatoid arthritis (RA) treatment adoptions are recommended in case of poor improvement in disease activity 3 months after initiating therapy with disease modifying anti-rheumatic drugs (DMARDs), or if remission or low disease activity (LDA) has not been reached by 6 months.¹ A pooled analyses from several pivotal RCTs showed that RA patients who did not achieve a minor treatment response within 3 months were unlikely to reach the treatment target by 6 months.² We aimed to investigate which response levels at 3 months are predictive of achieving the treatment targets at 6 months in a routine clinical setting.

Methods : Data were provided by NOR-DMARD, a prospective, multicentre, observational study. We selected biological DMARD-naïve RA-patients enrolled in the period 2000-2012, who had at least moderate disease activity according to the Simplified Disease Activity Index (SDAI) when initiating therapy. All analyses were performed for the total group of included patients (n=1610), as well as for the following sub-groups: disease duration more/ less than 12 months (n=895/681), baseline SDAI moderate/ high disease activity (n=825/ 785), DMARD-naïve patients starting methotrexate (n=237) and biological DMARD-naïve patients starting a tumour necrosis factor inhibitor (n=248). We used a diagnostic test approach with receiver operating characteristic curves to explore the association between SDAI 50/70/85 response at 3 months and achievement of the treatment targets of SDAI remission or SDAI LDA at 6 months.

Results: At inclusion mean (SD) SDAI was 28.3 (12.8) and median (25-75% percentile) disease duration was 2 (0.2-8.8) years. At 6 months 46.8% of all patients had achieved LDA and 10.8% had reached remission. Not achieving at least 50% SDAI response at 3 months was associated with failing to reach remission, with low negative likelihood ratios (LRs) for all analysed groups (LR- 0.15-0.36). Patients with high disease activity at baseline were likely to fail reaching remission at 6 months if they achieved less than SDAI 70% response at 3 months (LR- 0.25), and to not reach LDA if they achieved less than SDAI 50% response (LR- 0.30). Achieving SDAI 85% response at 3 months was associated with reaching the treatment targets in all analysed groups, with high positive LRs for both remission (LR+ 4.77-9.64) and LDA (LR+ 4.56-8.06).

Conclusion : These results from a routine clinical setting confirm results from RCTs demonstrating a predictive association between levels of treatment response at 3 months and achievement of the treatment target after 6 months in RA-patients. Assessments at 3 months can inform clinicians to continue or adjust ongoing DMARD-therapy in a treat-to-target strategy aiming for remission or LDA within 6 months.

References:

1.       Smolen JS, et al. Ann Rheum Dis 2017

2.       Aletaha D, et al. Ann Rheum Dis 2016