Top

Published in:

Open Access 01-12-2016 | Research article

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

Authors: Lotte Heimans, Gülşah Akdemir, Kirsten V. C. Wevers-de Boer, Yvonne P. Goekoop-Ruiterman, Esmeralda T. Molenaar, Johannes H. L. M. van Groenendael, Andreas J. Peeters, Gerda M. Steup-Beekman, Leroy R. Lard, Peter B. J. de Sonnaville, Bernard A. M. Grillet, Tom W. J. Huizinga, Cornelia F. Allaart

Published in: Arthritis Research & Therapy | Issue 1/2016

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.

Available only for authorised users

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.CrossRefPubMed

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.CrossRefPubMed

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.CrossRefPubMed

Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham III CO, 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.CrossRefPubMed

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.CrossRefPubMed

Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, et al. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis. 2010;69(3):510–6.PubMedCentralCrossRefPubMed

Machold KP, Landewe R, Smolen JS, Stamm TA, van der Heijde DM, Verpoort KN, et al. The Stop Arthritis Very Early (SAVE) trial, an international multicentre, randomised, double-blind, placebo-controlled trial on glucocorticoids in very early arthritis. Ann Rheum Dis. 2010;69(3):495–502.CrossRefPubMed

Marzo-Ortega H, Green MJ, Keenan AM, Wakefield RJ, Proudman S, Emery P. A randomized controlled trial of early intervention with intraarticular corticosteroids followed by sulfasalazine versus conservative treatment in early oligoarthritis. Arthritis Rheum. 2007;57(1):154–60.CrossRefPubMed

Saleem B, Mackie S, Quinn M, Nizam S, Hensor E, Jarrett S, et al. Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis? Ann Rheum Dis. 2008;67(8):1178–80.CrossRefPubMed

10.

van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, et al. Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2007;56(5):1424–32.CrossRefPubMed

11.

van Eijk IC, Nielen MM, van der Horst-Bruinsma I, Tijhuis GJ, Boers M, Dijkmans BA, et al. Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial. Rheumatology (Oxford). 2012;51(4):686–94.CrossRef

12.

Verstappen SM, McCoy MJ, Roberts C, Dale NE, Hassell AB, Symmons DP. Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial. Ann Rheum Dis. 2010;69(3):503–9.CrossRefPubMed

13.

Wevers-de Boer KVC, Visser K, Heimans L, Ronday HK, Molenaar E, Groenendael JH, et al. Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study). Ann Rheum Dis. 2012;71(9):1472–7.CrossRefPubMed

14.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52(11):3381–90.CrossRefPubMed

15.

Ma MH, Scott IC, Kingsley GH, Scott DL. Remission in early rheumatoid arthritis. J Rheumatol. 2010;37(7):1444–53.CrossRefPubMed

16.

Klarenbeek NB, Güler-Yüksel M, van der Kooij SM, Han KH, Ronday HK, Kerstens PJ, et al. The impact of four dynamic, goal-steered treatment strategies on the 5-year outcomes of rheumatoid arthritis patients in the BeSt study. Ann Rheum Dis. 2011;70(6):1039–46.CrossRefPubMed

17.

Leirisalo-Repo M, Kautiainen H, Laasonen L, Korpela M, Kauppi MJ, Kaipiainen-Seppanen O, et al. Infliximab for 6 months added on combination therapy in early rheumatoid arthritis: 2-year results from an investigator-initiated, randomised, double-blind, placebo-controlled study (the NEO-RACo Study). Ann Rheum Dis. 2013;72(6):851–7.CrossRefPubMed

18.

Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet. 1999;353(9164):1568–73.CrossRefPubMed

19.

Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997;350(9074):309–18.CrossRefPubMed

20.

ter Wee MM, den Uyl D, Boers M, Kerstens P, Nurmohamed M, van Schaardenburg D, et al. Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial. Ann Rheum Dis. 2015;74(6):1233–40.CrossRefPubMed

21.

van der Linden MP, le Cessie S, Raza K, van der Woude D, Knevel R, Huizinga TW, et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 2010;62(12):3537–46.CrossRefPubMed

22.

Heimans L, Wevers-de Boer KV, Visser K, Goekoop RJ, van Oosterhout M, Harbers JB, et al. A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study. Ann Rheum Dis. 2014;73(7):1356–61.CrossRefPubMed

23.

van der Heijde DM, van ‘t Hof MA, van Riel PL, Theunisse LA, Lubberts EW, van Leeuwen MA, et al. Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis. 1990;49(11):916–20.PubMedCentralCrossRefPubMed

24.

Prevoo ML, van Gestel AM, van T Hof M, van Rijswijk MH, van de Putte LB, van Riel PL. Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score. Br J Rheumatol. 1996;35(11):1101–5.CrossRefPubMed

25.

Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275–85.CrossRefPubMed

26.

Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, et al. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011;70(3):404–13.CrossRefPubMed

27.

Siegert CE, Vleming LJ, Vandenbroucke JP, Cats A. Measurement of disability in Dutch rheumatoid arthritis patients. Clin Rheumatol. 1984;3(3):305–9.CrossRefPubMed

28.

van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 1999;26(3):743–5.PubMed

29.

Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979;86(2):420–8.CrossRefPubMed

30.

Bruynesteyn K, van der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, et al. Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference. Arthritis Rheum. 2002;46(4):913–20.CrossRefPubMed

31.

van den Broek M, Dirven L, de Vries-Bouwstra JK, Dehpoor AJ, Goekoop-Ruiterman YP, Gerards AH, et al. Rapid radiological progression in the first year of early rheumatoid arthritis is predictive of disability and joint damage progression during 8 years of follow-up. Ann Rheum Dis. 2012;71(9):1530–3.CrossRefPubMed

32.

van Vollenhoven RF, Geborek P, Forslind K, Albertsson K, Ernestam S, Petersson IF, et al. Conventional combination treatment versus biological treatment in methotrexate-refractory early rheumatoid arthritis: 2 year follow-up of the randomised, non-blinded, parallel-group Swefot trial. Lancet. 2012;379(9827):1712–20.CrossRefPubMed

33.

O’Dell JR, Mikuls TR, Taylor TH, Ahluwalia V, Brophy M, Warren SR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369(4):307–18.CrossRefPubMed

34.

van den Broek M, Lems WF, Allaart CF. Do we need guidelines to stop as well as to start biological therapies for rheumatoid arthritis? Clin Exp Rheumatol. 2012;30(4 Suppl 73):S21–6.PubMed

35.

van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, van Zeben D, Kerstens PJ, Gerards AH, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. Ann Rheum Dis. 2007;66(10):1356–62.PubMedCentralCrossRefPubMed

36.

Klarenbeek NB, van der Kooij SM, Güler-Yüksel M, van Groenendael JH, Han KH, Kerstens PJ, et al. Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study. Ann Rheum Dis. 2011;70(2):315–9.CrossRefPubMed

Title: Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study)
Authors: Lotte Heimans
Gülşah Akdemir
Kirsten V. C. Wevers-de Boer
Yvonne P. Goekoop-Ruiterman
Esmeralda T. Molenaar
Johannes H. L. M. van Groenendael
Andreas J. Peeters
Gerda M. Steup-Beekman
Leroy R. Lard
Peter B. J. de Sonnaville
Bernard A. M. Grillet
Tom W. J. Huizinga
Cornelia F. Allaart
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-015-0912-y

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Trial registration

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2016

Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced arthritis by inducing host-derived indoleamine 2,3 dioxygenase

Frequency of circulating topoisomerase-I-specific CD4 T cells predicts presence and progression of interstitial lung disease in scleroderma

B cell depletion therapy upregulates Dkk-1 skin expression in patients with systemic sclerosis: association with enhanced resolution of skin fibrosis

Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review

Periodontal bacterial colonization in synovial tissues exacerbates collagen-induced arthritis in B10.RIII mice

Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome: a randomized controlled trial

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page