Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study

G. lsah Akdemir, Lotte Heimans, Sytske Anne Bergstra, Robbert J. Goekoop, Maikel van Oosterhout, Johannes H. L. M. van Groenendael, André 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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. Methods In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/ week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. Results After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR. O verall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/ van der Heijde points, with only five patients showing progression >25 points in 5 years. Conclusions Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.
Original languageEnglish
Pages (from-to)111-118
JournalAnnals of the Rheumatic Diseases
Volume77
Issue number1
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Akdemir, G. L., Heimans, L., Bergstra, S. A., Goekoop, R. J., van Oosterhout, M., van Groenendael, J. H. L. M., ... Allaart, C. F. (2018). Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study. Annals of the Rheumatic Diseases, 77(1), 111-118. https://doi.org/10.1136/annrheumdis-2017-211375
Akdemir, G. lsah ; Heimans, Lotte ; Bergstra, Sytske Anne ; Goekoop, Robbert J. ; van Oosterhout, Maikel ; van Groenendael, Johannes H. L. M. ; Peeters, André J. ; Steup-Beekman, Gerda M. ; Lard, Leroy R. ; de Sonnaville, Peter B. J. ; Grillet, Bernard A. M. ; Huizinga, Tom W. J. ; Allaart, Cornelia F. / Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study. In: Annals of the Rheumatic Diseases. 2018 ; Vol. 77, No. 1. pp. 111-118.
@article{ea97056578684cf88e1e127a2f2ae343,
title = "Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study",
abstract = "Objectives To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. Methods In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/ week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. Results After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48{\%}) patients were in remission, 26{\%} in sustained DFR (SDFR) (≥1 year) (220/387 (57{\%}) remission and 135/387 (35{\%}) SDFR in the early remission group, 50{\%} remission, 11{\%} SDFR in the randomisation arms without differences between the arms). More patients with UA (37{\%} vs 23{\%} RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37{\%} vs 18{\%} ACPA-positive, p<0.001) achieved SDFR. O verall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/ van der Heijde points, with only five patients showing progression >25 points in 5 years. Conclusions Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.",
author = "Akdemir, {G. lsah} and Lotte Heimans and Bergstra, {Sytske Anne} and Goekoop, {Robbert J.} and {van Oosterhout}, Maikel and {van Groenendael}, {Johannes H. L. M.} and Peeters, {Andr{\'e} J.} and Steup-Beekman, {Gerda M.} and Lard, {Leroy R.} and {de Sonnaville}, {Peter B. J.} and Grillet, {Bernard A. M.} and Huizinga, {Tom W. J.} and Allaart, {Cornelia F.}",
year = "2018",
doi = "10.1136/annrheumdis-2017-211375",
language = "English",
volume = "77",
pages = "111--118",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "1",

}

Akdemir, GL, Heimans, L, Bergstra, SA, Goekoop, RJ, van Oosterhout, M, van Groenendael, JHLM, Peeters, AJ, Steup-Beekman, GM, Lard, LR, de Sonnaville, PBJ, Grillet, BAM, Huizinga, TWJ & Allaart, CF 2018, 'Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study' Annals of the Rheumatic Diseases, vol. 77, no. 1, pp. 111-118. https://doi.org/10.1136/annrheumdis-2017-211375

Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study. / Akdemir, G. lsah; Heimans, Lotte; Bergstra, Sytske Anne; Goekoop, Robbert J.; van Oosterhout, Maikel; van Groenendael, Johannes H. L. M.; Peeters, André J.; Steup-Beekman, Gerda M.; Lard, Leroy R.; de Sonnaville, Peter B. J.; Grillet, Bernard A. M.; Huizinga, Tom W. J.; Allaart, Cornelia F.

In: Annals of the Rheumatic Diseases, Vol. 77, No. 1, 2018, p. 111-118.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study

AU - Akdemir, G. lsah

AU - Heimans, Lotte

AU - Bergstra, Sytske Anne

AU - Goekoop, Robbert J.

AU - van Oosterhout, Maikel

AU - van Groenendael, Johannes H. L. M.

AU - Peeters, André J.

AU - Steup-Beekman, Gerda M.

AU - Lard, Leroy R.

AU - de Sonnaville, Peter B. J.

AU - Grillet, Bernard A. M.

AU - Huizinga, Tom W. J.

AU - Allaart, Cornelia F.

PY - 2018

Y1 - 2018

N2 - Objectives To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. Methods In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/ week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. Results After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR. O verall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/ van der Heijde points, with only five patients showing progression >25 points in 5 years. Conclusions Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

AB - Objectives To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. Methods In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/ week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. Results After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR. O verall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/ van der Heijde points, with only five patients showing progression >25 points in 5 years. Conclusions Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/28970207

U2 - 10.1136/annrheumdis-2017-211375

DO - 10.1136/annrheumdis-2017-211375

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EP - 118

JO - Annals of the Rheumatic Diseases

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