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Efficacy of golimumab plus methotrexate in methotrexate-naïve patients with severe active rheumatoid arthritis

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Abstract

The purpose of this study was to assess the treatment benefit of golimumab + methotrexate (MTX) vs. MTX monotherapy in MTX-naïve patients with severe active rheumatoid arthritis (RA). This was a post hoc analysis of MTX-naïve RA patients in the GO-BEFORE trial who were randomized to receive placebo + MTX (n = 160), golimumab 50 mg + MTX (n = 159), or golimumab 100 mg + MTX (n = 159). Subsets of patients with severe disease were identified using these baseline criteria: C-reactive protein (CRP) ≥1.5 mg/dL, CRP ≥3.0 mg/dL, swollen joint count (SJC) ≥10 and tender joint count (TJC) ≥12, SJC ≥ 20/TJC ≥ 12, 28-joint count Disease Activity Score using CRP (DAS28-CRP) >5.1, and anti-cyclic citrullinated peptide antibody-positive status. The treatment effect of golimumab + MTX vs. MTX alone was evaluated for these outcomes: the proportions of patients achieving ≥20, 50, and 70 % improvement in the American College of Rheumatology criteria; DAS28-CRP European League Against Rheumatism response; DAS28-CRP <2.6, clinically meaningful improvement in physical function; and change in van der Heijde-Sharp score ≤0 at week 52. Clinical response was greater in the golimumab + MTX groups vs. placebo + MTX for all of the outcomes evaluated. Furthermore, the treatment effect of golimumab + MTX was consistently greater among patients in the severe disease subsets when compared with the overall GO-BEFORE trial population. The treatment benefit of golimumab + MTX vs. MTX monotherapy was most pronounced within the subsets of patients with CRP ≥3.0 mg/dL and SJC ≥ 20/TJC ≥ 12. Following treatment with golimumab + MTX, improvements in RA signs/symptoms and in progression of structural damage were evident for the overall GO-BEFORE population, with the treatment effect more pronounced among patients with severe active disease.

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References

  1. Prevoo ML, van’t MA H, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) 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 38(1):44–48

    Article  CAS  PubMed  Google Scholar 

  2. Smolen JS, van der Heijde DM, St Clair EW, Emery P, Bathon JM, Keystone E, Maini RN, Kalden JR, Schiff M, Baker D, Han C, Han J, Bala M (2006) 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 54(3):702–710

    Article  CAS  PubMed  Google Scholar 

  3. Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A, Nicaise-Roland P, Sibilia J, Combe B (2003) Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis 62(2):120–126

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Vencovsky J, Machacek S, Sedova L, Kafkova J, Gatterova J, Pesakova V, Ruzickova S (2003) Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Ann Rheum Dis 62(5):427–430

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Emery P, Fleischmann RM, Moreland LW, Hsia EC, Strusberg I, Durez P, Nash P, Amante EJ, Churchill M, Park W, Pons-Estel BA, Doyle MK, Visvanathan S, Xu W, Rahman MU (2009) Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum 60(8):2272–2283

    Article  CAS  PubMed  Google Scholar 

  6. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT (2006) 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 54(1):26–37

    Article  CAS  PubMed  Google Scholar 

  7. Rahman MU, Buchanan J, Doyle MK, Hsia EC, Gathany T, Parasuraman S, Aletaha D, Matteson EL, Conaghan PG, Keystone E, van der Heijde D, Smolen JS (2011) Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years. Ann Rheum Dis 70(9):1631–1640

    Article  PubMed Central  PubMed  Google Scholar 

  8. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V, Tugwell P, Weinblatt M, Williams JH, Wolfe F, Kieszak S (1995) American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38(6):727–735

  9. van Riel PL, van Gestel AM, Scott DL (2000) EULAR Handbook of clinical assessments in rheumatoid arthritis. Van Zuiden Communications, BV, Alphen Aan Den Rijn, The Netherlands

  10. Fries JF, Spitz P, Kraines RG, Holman HR (1980) Measurement of patient outcome in arthritis. Arthritis Rheum 23(2):137–145

    Article  CAS  PubMed  Google Scholar 

  11. Lubeck DP (2004) Patient-reported outcomes and their role in the assessment of rheumatoid arthritis. Pharmacoeconomics 22(2 Suppl 1):27–38

    PubMed  Google Scholar 

  12. van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van’t Hof MA, van Rijswijk MH, van de Putte LB (1992) Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum 35(1):26–34

    Article  PubMed  Google Scholar 

  13. Emery P, Fleischmann R, van der Heijde D, Keystone EC, Genovese MC, Conaghan PG, Hsia EC, Xu W, Baratelle A, Beutler A, Rahman MU (2011) The effects of golimumab on radiographic progression in rheumatoid arthritis: results of randomized controlled studies of golimumab before methotrexate therapy and golimumab after methotrexate therapy. Arthritis Rheum 63(5):1200–1210

    Article  CAS  PubMed  Google Scholar 

  14. Wagner CL, Visvanathan S, Elashoff M, McInnes IB, Mease PJ, Krueger GG, Murphy FT, Papp K, Gomez-Reino JJ, Mack M, Beutler A, Gladman D, Kavanaugh A (2013) Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab. Ann Rheum Dis 72(1):83–88

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O'Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG (2012) 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 (Hoboken) 64(5):625–639

    Article  CAS  Google Scholar 

  16. Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, Emery P, Gaujoux-Viala C, Gossec L, Nam J, Ramiro S, Winthrop K, de Wit M, Aletaha D, Betteridge N, Bijlsma JW, Boers M, Buttgereit F, Combe B, Cutolo M, Damjanov N, Hazes JM, Kouloumas M, Kvien TK, Mariette X, Pavelka K, van Riel PL, Rubbert-Roth A, Scholte-Voshaar M, Scott DL, Sokka-Isler T, Wong JB, van der Heijde D (2014) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 73(3):492–509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Quinn MA, Emery P (2003) Window of opportunity in early rheumatoid arthritis: possibility of altering the disease process with early intervention. Clin Exp Rheumatol 21(5 Suppl 31):S154–S157

    CAS  PubMed  Google Scholar 

  18. Baumgartner SW, Fleischmann RM, Moreland LW, Schiff MH, Markenson J, Whitmore JB (2004) Etanercept (Enbrel) in patients with rheumatoid arthritis with recent onset versus established disease: improvement in disability. J Rheumatol 31(8):1532–1537

    CAS  PubMed  Google Scholar 

  19. Lillegraven S, van der Heijde D, Uhlig T, Kvien TK, Haavardsholm EA (2012) What is the clinical relevance of erosions and joint space narrowing in RA? Nat Rev Rheumatol 8(2):117–120

    PubMed  Google Scholar 

  20. Anderson JJ, Wells G, Verhoeven AC, Felson DT (2000) Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 43(1):22–29

    Article  CAS  PubMed  Google Scholar 

  21. van der Heijde D, Breedveld FC, Kavanaugh A, Keystone EC, Landewe R, Patra K, Pangan AL (2010) Disease activity, physical function, and radiographic progression after longterm therapy with adalimumab plus methotrexate: 5-year results of PREMIER. J Rheumatol 37(11):2237–2246

    Article  PubMed  Google Scholar 

  22. van der Heijde D, Klareskog L, Landewe R, Bruyn GA, Cantagrel A, Durez P, Herrero-Beaumont G, Molad Y, Codreanu C, Valentini G, Zahora R, Pedersen R, MacPeek D, Wajdula J, Fatenejad S (2007) Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 56(12):3928–3939

    Article  PubMed  Google Scholar 

  23. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Furst D, Weisman MH, St Clair EW, Keenan GF, van der Heijde D, Marsters PA, Lipsky PE (2004) Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum 50(4):1051–1065

    Article  CAS  PubMed  Google Scholar 

  24. van der Kooij SM, le Cessie S, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Zeben D, Kerstens PJ, Hazes JM, van Schaardenburg D, Breedveld FC, Dijkmans BA, Allaart CF (2009) Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis. Ann Rheum Dis 68(7):1153–1158

    Article  PubMed  Google Scholar 

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Acknowledgments

Employees of Janssen Research & Development, LLC. participated in designing the study, collecting and analyzing the data, and writing and revising the manuscript. Additional writing and editorial support was provided by Rebecca E. Clemente, PhD, and Mary Whitman, PhD, of Janssen Scientific Affairs, LLC. All authors reviewed and approved the manuscript for submission.

Trial registration

EUDRACT No. 2004-003295-10; ClinicalTrials.gov NCT00264537

Conflict of interest

This work was supported by Janssen Research & Development, LLC. and Schering-Plough/Merck. The authors PE and RMF have served as consultants for and received grant support from Janssen Research & Development, LLC. The authors ECH, SX, YZ, and DB are employees of Janssen Research & Development, LLC., and own stock in Johnson & Johnson

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Authors and Affiliations

  1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK

    Paul Emery

  2. NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK

    Paul Emery

  3. University of Texas/Southwest Medical Center, Metroplex Clinical Research Center, Dallas, TX, USA

    Roy M. Fleischmann

  4. Immunology, Janssen Research & Development, LLC., Spring House, PA, USA

    Elizabeth C. Hsia & Daniel Baker

  5. School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Elizabeth C. Hsia

  6. Biostatistics, Janssen Research & Development, LLC., Spring House, PA, USA

    Stephen Xu & Yiying Zhou

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  1. Paul Emery
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  2. Roy M. Fleischmann
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  3. Elizabeth C. Hsia
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Correspondence to Paul Emery.

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Supplemental Table 1

Clinical efficacy at week 52 for the overall GO-BEFORE population and the severe disease subgroups. (DOCX 21 kb)

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Emery, P., Fleischmann, R.M., Hsia, E.C. et al. Efficacy of golimumab plus methotrexate in methotrexate-naïve patients with severe active rheumatoid arthritis. Clin Rheumatol 33, 1239–1246 (2014). https://doi.org/10.1007/s10067-014-2731-y

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  • DOI: https://doi.org/10.1007/s10067-014-2731-y

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