Low DAS at 4 months predicts sustained DMARD-free remission

Sustained disease-modifying anti-rheumatic drug (DMARD)-free remission (DFR), in this study defined as the absence of clinical arthritis for a minimum of 1 year after stopping DMARD(s), is increasingly achievable in anti-citrullinated protein/peptide antibody (ACPA)-negative and ACPA-positive rheumatoid arthritis (RA) [1,2].

Yet, the pathogenesis underlying sustained DFR-development is unclear; the presence of auto-antibodies, as well as patient characteristics at diagnosis are of importance, but do not exclusively explain sustained DFR [3]. This lack of understanding limits substantiated decisions to discontinue DMARD-treatment in clinical practice.

To gain more insight into sustained DFR in RA, Marloes Verstappen (Leiden University Medical Center, the Netherlands) and colleagues studied the course of disease activity scores (DAS) over time in relation to the development of sustained DFR, and investigated whether the time course of DAS may be helpful to identify patients who are likely to achieve sustained DFR [3]. This study comprised data from 772 RA patients included in the Leiden Early Arthritis Clinic from 1999 onwards. They were treated with initial methotrexate (first-choice treatment) and treat-to-target treatment (DAS-steered adjustments from 2005 onwards). Tapering or discontinuation of all DMARDs, including glucocorticosteroids, was done when DAS reached <2.4, in the absence of clinical arthritis. Patients were studied with a median follow-up of 7 years. The primary outcome of the study was sustained DFR. The course of DAS was compared between those who achieved sustained DFR within 7 years and those who did not. This was determined using linear mixed models, stratified for ACPA. Further, the relation was studied between DAS at 4 months and the probability of achieving sustained DFR within 7 years with logistic regression, and Kaplan-Meier curves were generated performed to show the cumulative incidence of sustained DFR for different DAS categories at 4 months (i.e. <1.6, 1.6-2.4, 2.4-3.6, >3.6).

The analysis showed that patients achieving sustained DFR had a remarkably different DAS response within 4 months after diagnosis. Compared with patients who did not achieve sustained DFR, the sustained DFR-group showed a prominently stronger decline in DAS between baseline and 4 months: 1.59 units decline (95% CI 1.24-1.95) versus 0.96 units (95% CI 0.85-1.07) decline (P<0.001) (see Figure). Stratification for ACPA yielded a similar and statistically significant effect in ACPA-negative RA, while in ACPA-positive RA, this effect was absent. In ACPA-negative RA, the probability of achieving sustained DFR during 7 years was lower for patients with higher DAS at 4 months. After 7 years of disease, the cumulative incidence for sustained DFR in ACPA-negative patients with DAS <1.6 at 4 months was high (71.0%), while sustained DFR was rare among those with DAS >3.6 at 4 months (7.1%).

The authors concluded that DAS levels at 4 months are predictive for sustained DFR in ACPA-negative patients, as those with sustained DFR showed a significant stronger DAS decline during the first 4 months after diagnosis. This may mean that the window of opportunity expands to the early phase after diagnosis, and that evaluation of early response to treatment is important in the decision-making to stop DMARDs. The DAS course was not associated with sustained DFR in patients with ACPA-positive RA.  Identification and stratification of the ACPA-negative RA subgroups going forward has implications for potentially minimising DMARD exposure.

Figure: Course of DAS over time in relation to sustained DFR achievement in ACPA-negative RA patients [3]

*Indicates significant stronger decline in DAS in SDFR-group.
ACPA, anti-citrullinated protein antibodies; DAS, disease activity score; SFDR, sustained DMARD-free remission.

1. Ajeganova S, et al. Ann Rheum Dis 2015;0:1-2.
2. Verstappen M, et al. RMD open 2020;6(1):e001220.
3. Verstappen M, et al. OP0235. EULAR E-Congress, 3-6 June 2020.

Posted on 14 August, 20205 August, 2021