Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone

Edward C Keystone, Ferdinand C Breedveld, Désirée van der Heijde, Ronald F van Vollenhoven, Paul Emery, Josef S Smolen, Iain Sainsbury, Stefan Florentinus, Hartmut Kupper, Kun Chen, Arthur Kavanaugh, Edward C Keystone, Ferdinand C Breedveld, Désirée van der Heijde, Ronald F van Vollenhoven, Paul Emery, Josef S Smolen, Iain Sainsbury, Stefan Florentinus, Hartmut Kupper, Kun Chen, Arthur Kavanaugh

Abstract

Objective: To evaluate the achievement of comprehensive disease control (CDC) following 1 year of treatment with adalimumab+methotrexate versus methotrexate alone and whether early achievement of remission (at week 24 or 26) is associated with CDC at week 52 in patients with either early or established rheumatoid arthritis (RA).

Methods: Post hoc analyses were conducted in three clinical studies assessing treatment with adalimumab+methotrexate: DE019 (NCT00195702) enrolled patients with established RA who were methotrexate inadequate responders; OPTIMA (NCT00420927) and PREMIER (NCT00195663) enrolled methotrexate-naive patients with early RA. In OPTIMA, patients not achieving stable low disease activity at weeks 22 and 26 in the placebo+methotrexate group could receive open-label adalimumab+methotrexate for 52 weeks (Rescue ADA arm). CDC was defined as the simultaneous achievement of clinical remission (DAS28(CRP)<2.6), normal function (HAQ-DI<0.5) and absence of radiographic progression (ΔmTSS≤0.5).

Results: Regardless of disease duration, significantly more patients receiving adalimumab+methotrexate achieved CDC compared with methotrexate alone. In the adalimumab+methotrexate group, a numerically greater proportion of patients with early RA (~25%) versus established RA (14%) achieved CDC at 1 year; achievement of CDC was notably greater among patients who met criteria for remission at week 24 or 26 (~50% of patients with early RA and 39% with established RA).

Conclusion: Treatment with adalimumab+methotrexate increases the likelihood of achieving CDC in patients with either early or established RA. Clinical remission at week 24 or 26 is associated with achievement of CDC at week 52.

Trial registration number: DE019 (NCT00195702), OPTIMA (NCT00420927), PREMIER (NCT00195663); Post-results.

Keywords: anti-TNF; methotrexate; rheumatoid arthritis; treatment.

Conflict of interest statement

Competing interests: ECK has received research grants, consulting fees and/or speaker fees from AbbVie, Amgen, AstraZeneca, Baylis Medical, Biotest, BMS, Genentech, Janssen, Lilly, Novartis, Nycomed, Pfizer, Roche, Sanofi-Aventis and UCB. FCB has received consulting fees from AbbVie, Amgen/Wyeth, Centocor and Schering-Plough. DH has received research grants and consulting fees from AbbVie, Amgen, AstraZeneca, BMS, Centocor, Chugai, Daiichi, Eli Lilly, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, and Vertex, and is the Director of Imaging Rheumatology BV. RFV has received research grants and/or consulting fees from AbbVie, Biotest, BMS, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB and Vertex. PE has received research grants and/or consulting fees from AbbVie, BMS, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz and UCB. IS, SF, HK and KC are full-time employees of AbbVie and may hold stock and/or options. JSS has received research grants, consulting fees and speaker fees from AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Glaxo, Lilly, Pfizer (Wyeth), MSD (Schering-Plough), Novo-Nordisk, Roche, Sandoz and UCB. AK has received research grants and consulting fees from AbbVie, Amgen, AstraZeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche and UCB.

Figures

Figure 1
Figure 1
Percentage of patients achieving comprehensive disease control based on DAS28(CRP)≤3.2, DAS28(CRP)

Figure 2

Frequency of responders to each…

Figure 2

Frequency of responders to each CDC criterion (DAS28(CRP)

Figure 2
Frequency of responders to each CDC criterion (DAS28(CRP)

Figure 3

Frequency of responders to each…

Figure 3

Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI

Figure 3
Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI

Figure 4

Percentage of patients with RA…

Figure 4

Percentage of patients with RA achieving DAS28(CRP)

Figure 4
Percentage of patients with RA achieving DAS28(CRP)
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References
    1. Sangha O. Epidemiology of rheumatic diseases. Rheumatology 2000;39(Suppl 2):3–12. 10.1093/rheumatology/39.suppl_2.3 - DOI - PubMed
    1. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. . Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp’s method (van der Heijde modification). J Rheumatol 1995;22:1792–6. - PubMed
    1. Lindqvist E, Jonsson K, Saxne T, et al. . Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis. Ann Rheum Dis 2003;62:611–6. 10.1136/ard.62.7.611 - DOI - PMC - PubMed
    1. Aletaha D, Smolen J, Ward MM. Measuring function in rheumatoid arthritis: Identifying reversible and irreversible components. Arthritis Rheum 2006;54:2784–92. 10.1002/art.22052 - DOI - PubMed
    1. Emery P, Breedveld FC, Dougados M, et al. . Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:290–7. 10.1136/ard.61.4.290 - DOI - PMC - PubMed
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Figure 2
Figure 2
Frequency of responders to each CDC criterion (DAS28(CRP)

Figure 3

Frequency of responders to each…

Figure 3

Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI

Figure 3
Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI

Figure 4

Percentage of patients with RA…

Figure 4

Percentage of patients with RA achieving DAS28(CRP)

Figure 4
Percentage of patients with RA achieving DAS28(CRP)
Similar articles
Cited by
References
    1. Sangha O. Epidemiology of rheumatic diseases. Rheumatology 2000;39(Suppl 2):3–12. 10.1093/rheumatology/39.suppl_2.3 - DOI - PubMed
    1. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. . Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp’s method (van der Heijde modification). J Rheumatol 1995;22:1792–6. - PubMed
    1. Lindqvist E, Jonsson K, Saxne T, et al. . Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis. Ann Rheum Dis 2003;62:611–6. 10.1136/ard.62.7.611 - DOI - PMC - PubMed
    1. Aletaha D, Smolen J, Ward MM. Measuring function in rheumatoid arthritis: Identifying reversible and irreversible components. Arthritis Rheum 2006;54:2784–92. 10.1002/art.22052 - DOI - PubMed
    1. Emery P, Breedveld FC, Dougados M, et al. . Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:290–7. 10.1136/ard.61.4.290 - DOI - PMC - PubMed
Show all 51 references
Associated data
Related information
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Figure 3
Figure 3
Frequency of responders to each CDC criterion (SDAI≤3.3, HAQ-DI

Figure 4

Percentage of patients with RA…

Figure 4

Percentage of patients with RA achieving DAS28(CRP)

Figure 4
Percentage of patients with RA achieving DAS28(CRP)
Similar articles
Cited by
References
    1. Sangha O. Epidemiology of rheumatic diseases. Rheumatology 2000;39(Suppl 2):3–12. 10.1093/rheumatology/39.suppl_2.3 - DOI - PubMed
    1. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. . Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp’s method (van der Heijde modification). J Rheumatol 1995;22:1792–6. - PubMed
    1. Lindqvist E, Jonsson K, Saxne T, et al. . Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis. Ann Rheum Dis 2003;62:611–6. 10.1136/ard.62.7.611 - DOI - PMC - PubMed
    1. Aletaha D, Smolen J, Ward MM. Measuring function in rheumatoid arthritis: Identifying reversible and irreversible components. Arthritis Rheum 2006;54:2784–92. 10.1002/art.22052 - DOI - PubMed
    1. Emery P, Breedveld FC, Dougados M, et al. . Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:290–7. 10.1136/ard.61.4.290 - DOI - PMC - PubMed
Show all 51 references
Associated data
Related information
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 4
Figure 4
Percentage of patients with RA achieving DAS28(CRP)

References

    1. Sangha O. Epidemiology of rheumatic diseases. Rheumatology 2000;39(Suppl 2):3–12. 10.1093/rheumatology/39.suppl_2.3
    1. van der Heijde DM, van Leeuwen MA, van Riel PL, et al. . Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp’s method (van der Heijde modification). J Rheumatol 1995;22:1792–6.
    1. Lindqvist E, Jonsson K, Saxne T, et al. . Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis. Ann Rheum Dis 2003;62:611–6. 10.1136/ard.62.7.611
    1. Aletaha D, Smolen J, Ward MM. Measuring function in rheumatoid arthritis: Identifying reversible and irreversible components. Arthritis Rheum 2006;54:2784–92. 10.1002/art.22052
    1. Emery P, Breedveld FC, Dougados M, et al. . Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Ann Rheum Dis 2002;61:290–7. 10.1136/ard.61.4.290
    1. Smolen JS, Aletaha D, Bijlsma JW, et al. . Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010;69:631–7. 10.1136/ard.2009.123919
    1. Emery P, Kavanaugh A, Bao Y, et al. . Comprehensive disease control (CDC): what does achieving CDC mean for patients with rheumatoid arthritis? Ann Rheum Dis 2015;74:2165–74. 10.1136/annrheumdis-2014-205302
    1. Aletaha D, Strand V, Smolen JS, et al. . Treatment-related improvement in physical function varies with duration of rheumatoid arthritis: a pooled analysis of clinical trial results. Ann Rheum Dis 2008;67:238–43. 10.1136/ard.2007.071415
    1. Schoels M, Knevel R, Aletaha D, et al. . Evidence for treating rheumatoid arthritis to target: results of a systematic literature search. Ann Rheum Dis 2010;69:638–43. 10.1136/ard.2009.123976
    1. Knevel R, Schoels M, Huizinga TW, et al. . Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis 2010;69:987–94. 10.1136/ard.2009.126748
    1. van der Heijde D, Breedveld FC, Kavanaugh A, et al. . Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER. J Rheumatol 2010;37:2237–46. 10.3899/jrheum.100208
    1. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, 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;52:3381–90. 10.1002/art.21405
    1. Smolen JS, Landewé R, Breedveld FC, et al. . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014;73:492–509. 10.1136/annrheumdis-2013-204573
    1. Barnabe C, Homik J, Barr SG, et al. . The effect of different remission definitions on identification of predictors of both point and sustained remission in rheumatoid arthritis treated with anti-TNF therapy. J Rheumatol 2014;41:1607–13. 10.3899/jrheum.131451
    1. Aletaha D, Funovits J, Keystone EC, et al. . Disease activity early in the course of treatment predicts response to therapy after one year in rheumatoid arthritis patients. Arthritis Rheum 2007;56:3226–35. 10.1002/art.22943
    1. Verstappen SM, van Albada-Kuipers GA, Bijlsma JW, et al. . A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up. Ann Rheum Dis 2005;64:38–43. 10.1136/ard.2003.014928
    1. Keystone EC, Kavanaugh AF, Sharp JT, et al. . Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004;50:1400–11. 10.1002/art.20217
    1. Breedveld FC, Weisman MH, Kavanaugh AF, et al. . The PREMIER study: a multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 2006;54:26–37. 10.1002/art.21519
    1. Kavanaugh A, Fleischmann RM, Emery P, et al. . Clinical, functional and radiographic consequences of achieving stable low disease activity and remission with adalimumab plus methotrexate or methotrexate alone in early rheumatoid arthritis: 26-week results from the randomised, controlled OPTIMA study. Ann Rheum Dis 2013;72:64–71. 10.1136/annrheumdis-2011-201247
    1. Smolen JS, Emery P, Fleischmann R, et al. . Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet 2014;383:321–32. 10.1016/S0140-6736(13)61751-1
    1. Arnett FC, Edworthy SM, Bloch DA, et al. . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24. 10.1002/art.1780310302
    1. Soubrier M, Zerkak D, Gossec L, et al. . Which variables best predict change in rheumatoid arthritis therapy in daily clinical practice? J Rheumatol 2006;33:1243–6.
    1. Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol 2005;23(5 Suppl 39):S93–9.
    1. Singh JA, Furst DE, Bharat A, et al. . 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res 2012. 64:625–39. 10.1002/acr.21641
    1. Shammas RM, Ranganath VK, Paulus HE. Remission in rheumatoid arthritis. Curr Rheumatol Rep 2010;12:355–62. 10.1007/s11926-010-0121-2
    1. Smolen JS, Breedveld FC, Schiff MH, et al. . A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Rheumatology 2003;42:244–57. 10.1093/rheumatology/keg072
    1. Prevoo ML, van’t Hof MA, Kuper HH, et al. . Modified disease activity scores that include twenty-eight-joint counts. development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8. 10.1002/art.1780380107
    1. van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 1998;41:1845–50. 10.1002/1529-0131(199810)41:10<1845::AID-ART17>;2-K
    1. Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the health assessment questionnaire, disability and pain scales. J Rheumatol 1982;9:789–93.
    1. Felson DT, Smolen JS, Wells G, et al. . American College of Rheumatology/European League against rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis 2011;70:404–13. 10.1136/ard.2011.149765
    1. Hochberg MC, Chang RW, Dwosh I, et al. . The American College of Rheumatology 1991 revised criteria for the classification of global functional status in rheumatoid arthritis. Arthritis Rheum 1992;35:498–502. 10.1002/art.1780350502
    1. van der Heijde D. How to read radiographs according to the sharp/van der heijde method. J Rheumatol 1999;26:743–5.
    1. Sharp JT, Lidsky MD, Collins LC, et al. . Methods of scoring the progression of radiologic changes in rheumatoid arthritis. correlation of radiologic, clinical and laboratory abnormalities. Arthritis Rheum 1971;14:706–20. 10.1002/art.1780140605
    1. Plant MJ, Saklatvala J, Borg AA, et al. . Measurement and prediction of radiological progression in early rheumatoid arthritis. J Rheumatol 1994;21:1808–13.
    1. van der Heijde D, Simon L, Smolen J, et al. . How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Arthritis Rheum 2002;47:215–8. 10.1002/art.10181
    1. Klareskog L, van der Heijde D, de Jager JP, et al. . Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675–81. 10.1016/S0140-6736(04)15640-7
    1. Lipsky PE, van der Heijde DM, St Clair EW, et al. . Infliximab and methotrexate in the treatment of rheumatoid arthritis. anti-tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study group. N Engl J Med 2000;343:1594–602. 10.1056/NEJM200011303432202
    1. Klarenbeek NB, Koevoets R, van der Heijde DM, et al. . Association with joint damage and physical functioning of nine composite indices and the 2011 ACR/EULAR remission criteria in rheumatoid arthritis. Ann Rheum Dis 2011;70:1815–21. 10.1136/ard.2010.149260
    1. Gaujoux-Viala C, Mouterde G, Baillet A, et al. . Evaluating disease activity in rheumatoid arthritis: which composite index is best? a systematic literature analysis of studies comparing the psychometric properties of the DAS, DAS28, SDAI and CDAI. Joint Bone Spine 2012;79:149–55. 10.1016/j.jbspin.2011.04.008
    1. Fleischmann R, van der Heijde D, Koenig AS, et al. . How much does disease activity score in 28 joints ESR and CRP calculations underestimate disease activity compared with the simplified disease activity index? Ann Rheum Dis 2015;74:1132–7. 10.1136/annrheumdis-2013-204920
    1. Smolen JS, Van Der Heijde DM, St Clair EW, et al. . Predictors of joint damage in patients with early rheumatoid arthritis treated with high-dose methotrexate with or without concomitant infliximab: results from the ASPIRE trial. Arthritis Rheum 2006;54:702–10. 10.1002/art.21678
    1. Verschueren P, Esselens G, Westhovens R. Predictors of remission, normalized physical function, and changes in the working situation during follow-up of patients with early rheumatoid arthritis: an observational study. Scand J Rheumatol 2009;38:166–72. 10.1080/03009740802484846
    1. Combe B, Cantagrel A, Goupille P, et al. . Predictive factors of 5-year health assessment questionnaire disability in early rheumatoid arthritis. J Rheumatol 2003;30:2344–9.
    1. Drossaers-Bakker KW, de Buck M, van Zeben D, et al. . Long-term course and outcome of functional capacity in rheumatoid arthritis: the effect of disease activity and radiologic damage over time. Arthritis Rheum 1999;42:1854–60. 10.1002/1529-0131(199909)42:9<1854::AID-ANR9>;2-F
    1. Welsing PM, van Gestel AM, Swinkels HL, et al. . The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum 2001;44:2009–17. 10.1002/1529-0131(200109)44:9<2009::AID-ART349>;2-L
    1. Radner H, Smolen JS, Aletaha D. Remission in rheumatoid arthritis: benefit over low disease activity in patient-reported outcomes and costs. Arthritis Res Ther 2014;16:R56 10.1186/ar4491
    1. Kuriya B, Xiong J, Boire G, et al. . Earlier time to remission predicts sustained clinical remission in early rheumatoid arthritis--results from the Canadian Early Arthritis Cohort (CATCH). J Rheumatol 2014;41:2161–6. 10.3899/jrheum.140137
    1. Schipper LG, Fransen J, den Broeder AA, et al. . Time to achieve remission determines time to be in remission. Arthritis Res Ther 2010;12:R97 10.1186/ar3027
    1. Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol 2005;23(5 Suppl 39):S100–8.
    1. Aletaha D, Ward MM, Machold KP, et al. . Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 2005;52:2625–36. 10.1002/art.21235
    1. Benka J, Nagyova I, Rosenberger J, et al. . Social participation in early and established rheumatoid arthritis patients. Disabil Rehabil 2016;38:1172–9. 10.3109/09638288.2015.1076071

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