Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 23;22(1):276.
doi: 10.1186/s13075-020-02368-9.

Early DAS response after DMARD-start increases probability of achieving sustained DMARD-free remission in rheumatoid arthritis

M Verstappen  1 , E Niemantsverdriet  2 , X M E Matthijssen  2 , S le Cessie  3   4 , A H M van der Helm-van Mil  2   5
Affiliations

Early DAS response after DMARD-start increases probability of achieving sustained DMARD-free remission in rheumatoid arthritis

M Verstappen et al. Arthritis Res Ther. .

Abstract

Background: Sustained DMARD-free remission (SDFR) is increasingly achievable. The pathogenesis underlying SDFR development is unknown and patient characteristics at diagnosis poorly explain whether SDFR will be achieved. To increase the understanding, we studied the course of disease activity scores (DAS) over time in relation to SDFR development. Subsequently, we explored whether DAS course could be helpful identifying RA patients likely to achieve SDFR.

Methods: 772 consecutive RA patients, promptly treated with csDMARDs (mostly methotrexate and treat-to-target treatment adjustments), were studied for SDFR development (absence of synovitis, persisting minimally 12 months after DMARD stop). The course of disease activity scores (DAS) was compared between RA patients with and without SDFR development within 7 years, using linear mixed models, stratified for ACPA. The relation between 4-month DAS and the probability of SDFR development was studied with logistic regression. Cumulative incidence of SDFR within DAS categories (< 1.6, 1.6-2.4, 2.4-3.6, ≥ 3.6) at 4 months was visualized using Kaplan-Meier curves.

Results: In ACPA-negative RA patients, those achieving SDFR showed a remarkably stronger DAS decline within the first 4 months, compared to RA patients without SDFR; - 1.73 units (95%CI, 1.28-2.18) versus - 1.07 units (95%CI, 0.90-1.23) (p < 0.001). In APCA-positive RA patients, such an effect was not observed, yet SDFR prevalence in this group was low. In ACPA-negative RA, DAS decline in the first 4 months and absolute DAS levels at 4 months (DAS4 months) were equally predictive for SDFR development. Incidence of SDFR in ACPA-negative RA patients was high (70.2%) when DAS4 months was < 1.6, whilst SDFR was rare (7.1%) when DAS4 months was ≥ 3.6.

Conclusions: In ACPA-negative RA, an early response to treatment, i.e., a strong DAS decline within the first 4 months, is associated with a higher probability of SDFR development. DAS values at 4 months could be useful for later decisions to stop DMARDs.

Keywords: Anti-citrullinated protein antibodies; DMARD-free remission; Disease activity scores; Drug-free remission; Rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

Fig. 1
Fig. 1
Course of DAS over time for the SDFR and non-SDFR group in the total RA population studied, and for ACPA-negative RA and ACPA-positive RA separately. Legend: Course of DAS over time of patients achieving sustained DMARD-free remission (SDFR) within 7 years of follow-up (n = 149), and those not (n = 623). In ACPA-positive patients, the line of the SDFR group was restricted to 5 years of follow-up because of insufficient data thereafter. Statistically significant differences in course of DAS over time, between the SDFR group and non-SDFR group, were indicated by with *. ACPA anti-citrullinated protein antibody, DAS disease activity scores, RA rheumatoid arthritis, SDFR sustained DMARD-free remission
Fig. 2
Fig. 2
Course of DAS components over time for the SDFR- and non-SDFR group in all RA patients. Legend: Course of DAS components over time of patients achieving sustained DMARD-free remission (SDFR) within 7 years of follow-up, and those not. Statistically significant differences in course of DAS over time, between the SDFR group and non-SDFR group, were indicated by with *. DAS disease activity scores, RA rheumatoid arthritis, SDFR sustained DMARD-free remission
Fig. 3
Fig. 3
Predicted probability of SDFR development in ACPA negative RA in relation to DAS at 4 months. Legend: Predicted probability of achieving SDFR during follow-up in ACPA-negative RA, based on multivariate logistic model including DAS at 4 months, age, gender, and symptom duration (Table 2). For this graph, age, gender, and symptom duration were set at the mean value of each covariable. An inverse relation is seen between DAS at 4 months and the predicted probability of achieving SDFR (within 7 years). ACPA anti-citrullinated protein antibody, DAS disease activity score, SDFR sustained DMARD-free remission
Fig. 4
Fig. 4
Kaplan-Meier curves for SDFR development within 7 years of follow-up based on disease activity scores at 4 months in ACPA-negative RA. Legend: Time-to-event was defined as time from 4 months visit until SDFR development (yes/no), i.e., the absence of clinical arthritis for minimally 12 months after DMARD stop. ACPA anti-citrullinated protein antibody, DAS disease activity score, SDFR sustained DMARD-free remission
See this image and copyright information in PMC

References

    1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19. - PubMed
    1. Ajeganova S, van Steenbergen HW, van Nies JA, Burgers LE, Huizinga TW, van der Helm-van Mil AH. Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms. Ann Rheum Dis. 2016;75(5):867–873. doi: 10.1136/annrheumdis-2014-207080. - DOI - PubMed
    1. Matthijssen XME, Niemantsverdriet E, Huizinga TWJ, van der Helm–van Mil AHM. Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands. PLOS Medicine. 2020;17(9):e1003296. - PMC - PubMed
    1. Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. 2020:annrheumdis-2019-216655. - PubMed
    1. Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249–262. doi: 10.1177/1759720X17720366. - DOI - PMC - PubMed

Publication types