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
Randomized Controlled Trial
. 2016 Jan 21:18:23.
doi: 10.1186/s13075-015-0912-y.

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study)

Lotte Heimans  1 , Gülşah Akdemir  2 , Kirsten V C Wevers-de Boer  3 , Yvonne P Goekoop-Ruiterman  4 , Esmeralda T Molenaar  5 , Johannes H L M van Groenendael  6 , Andreas J Peeters  7 , Gerda M Steup-Beekman  8 , Leroy R Lard  9 , Peter B J de Sonnaville  10 , Bernard A M Grillet  11 , Tom W J Huizinga  12 , Cornelia F Allaart  13
Affiliations
Randomized Controlled Trial

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study)

Lotte Heimans et al. Arthritis Res Ther. .

Abstract

Background: Early suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients.

Methods: Patients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA.

Results: After 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0-0).

Conclusions: After 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed.

Trial registration: http://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Study flow chart with percentages disease activity score (DAS) and drug-free remission after the second study year. Orange prednisone, green methotrexate (MTX), dark blue treatment according to opinion of rheumatologist (TAR), aqua hydroxychloroquine (HCQ), yellow sulfasalazine (SSZ), purple adalimumab biweekly, double thickness purple adalimumab weekly, grey protocol not followed as required but remained in follow up (outside of protocol, OOP). DFR drug-free remission
Fig. 2
Fig. 2
Mean disease activity score (DAS) and health assessment questionnaire (HAQ) according to treatment group during 2 years of follow up. OOP outside of protocol
Fig. 3
Fig. 3
Treatment over time in the early remission group (a), Arm 1 (b) and Arm 2 (c), in percentage of total per treatment group; percentages in disease activity score (DAS)-remission and percentages in drug-free remission (DFR) (d). a Early remission group; b Arm 1; c. Arm 2. Lines are approximations of the proportions of patients discontinuing medication (according to tapering strategies or due to side effects), or starting medications according to DAS-remission-steered escalation strategies, across various treatment steps per arm, over time. The category Other includes medications that were prescribed per protocol in the ‘treatment according to rheumatologist’ step after failure on methotrexate plus adalimumab, and medications prescribed outside of the protocol but still maintaining a DAS-remission-targeted strategy. Shaded areas denote patient proportions in DAS-remission over time. d. Proportions of patients in DAS-remission and DFR per strategy over time. MTX methotrexate, pred prednisone, SSZ sulphasalazine, HCQ hydroxychloroquine, ADA adalimumab, mono monotherapy, DFR drug-free (DAS) remission, LTFO lost to follow up, ER early remission
See this image and copyright information in PMC

References

    1. Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263–9. doi: 10.1016/S0140-6736(04)16676-2. - DOI - PubMed
    1. Puolakka K, Kautiainen H, Mottonen T, Hannonen P, Korpela M, Hakala M, et al. Early suppression of disease activity is essential for maintenance of work capacity in patients with recent-onset rheumatoid arthritis: five-year experience from the FIN-RACo trial. Arthritis Rheum. 2005;52(1):36–41. doi: 10.1002/art.20716. - DOI - PubMed
    1. van Tuyl LH, Lems WF, Voskuyl AE, Kerstens PJ, Garnero P, Dijkmans BA, et al. Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90 % remission in a pilot trial. Ann Rheum Dis. 2008;67(11):1574–7. doi: 10.1136/ard.2008.090712. - DOI - PubMed
    1. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, III, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580–8. doi: 10.1136/ard.2010.138461. - DOI - PubMed
    1. de Jong PH, Hazes JM, Barendregt PJ, Huisman M, van Zeben D, van der Lubbe PA, et al. Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial. Ann Rheum Dis. 2013;72(1):72–8. doi: 10.1136/annrheumdis-2011-201162. - DOI - PubMed

Publication types