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Response to methotrexate predicts long-term patient-related outcomes in rheumatoid arthritis

Abstract

This study was conducted to investigate the predictive value of the initial response to methotrexate (MTX) on long-term patient-related outcomes (PROs) in rheumatoid arthritis (RA). All RA patients starting MTX treatment between 1980 and 1987 in our department were enrolled in a prospective observational study. After an average of 18 years, patient-related outcomes were assessed in three dimensions according to the International Classification of Functioning, Disability and Health (ICF). Statistical analyses employed multivariable models with baseline values for age, gender, disease duration, rheumatoid factor positivity, disease activity, response to MTX after 1 year and continuous use of MTX as covariates. The 271 patients enrolled had a mean disease duration of 8.5 years, a mean number of swollen joints of 18 (out of 32), and a mean erythrocyte sedimentation rate of 55 mm/h. After 18 years, PRO was available in 89 patients (33 %). A clinical improvement of at least 20 % 1 year after the initiation of MTX was associated with a favourable outcome in all three dimensions of the ICF, independent of continuation of MTX (p < 0.05). The initial response to MTX is an independent predictor of PRO in RA as assessed after an average of 18 years.

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References

  1. 1.

    El Miedany Y (2013) PROMs in inflammatory arthritis: moving from static to dynamic. Clin Rheumatol 32:735–742

    Article  PubMed  Google Scholar 

  2. 2.

    Kingsley G, Scott IC, Scott DL (2011) Quality of life and the outcome of established rheumatoid arthritis. Best Pract Res Clin Rheumatol 25:585–606

    Article  PubMed  Google Scholar 

  3. 3.

    Malm K, Bergman S, Andersson M, Bremander A, BARFOT study group (2015) Predictors of severe self-reported disability in RA in a long-term follow-up study. Disabil Rehabil 37:686–691

    Article  PubMed  Google Scholar 

  4. 4.

    Tanaka E, Mannalithara A, Inoue E, Hara M, Tomatsu T, Kamatani N, Singh G, Jamanaka H (2008) Efficient management of rheumatoid arthritis significantly reduces long-term functional disability. Ann Rheum Dis 67:1153–1158

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Balsa A, Del Amo J, Blanco F et al (2010) Prediction of functional impairment and remission in rheumatoid arthritis patients by biochemical variables and genetic polymorphisms. Rheumatology (Oxford) 49:458–466

    CAS  Article  Google Scholar 

  6. 6.

    Combe B, Logeart I, Belkacemi MC, Dadoun S, Schaeverbeke T, Daurès JP, Dougados M (2015) Comparison of the long-term outcome for patients with rheumatoid arthritis with persistent moderate disease activity or disease remission during the first year after diagnosis: data from the ESPOIR cohort. Ann Rheum Dis 74:724–729

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Lopez-Olivo MA, Siddhanamatha HR, Shea B, Tugwell P, Wells GA, Suarez-Almazor ME (2014) Methotrexate for treating rheumatoid arthritis. Cochrane Database Syst Rev 6:CD000957. doi:10.1002/14651858.CD000957.pub2

    PubMed  Google Scholar 

  8. 8.

    Singh JA, Furst DE, Bharat A et al (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 64:625–639

    CAS  Article  Google Scholar 

  9. 9.

    Smolen JS, Landewé R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Krause D, Schleusser B, Herborn W, Rau R (2000) Response to methotrexate is associates with reduced mortality in patients with severe rheumatoid arthritis. Arthritis Rheum 43:14–21

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Wilke WS, Calabrese LH, Scherbel AL (1980) Methotrexate in the treatment of rheumatoid arthritis; pilot study. Cleve Clin Q 47:305–309

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Weinblatt ME, Coblyn JS, Fox DA, Fraser PA, Holdsworth DE, Glass DN, Trendham DE (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 312:818–822

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    World Health Organization Assessment, Classification and Epidemiology Group (1999) International Classification of Functioning, Disability and Health. World Health Organization, Geneva

    Google Scholar 

  14. 14.

    Ropes MW, Bennett GA, Cobb S, Jacox RF, Jessar RA (1995) 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–176

    Google Scholar 

  15. 15.

    Krause D, Gabriel B, Herborn G, Braun J, Rau R (2014) The positive influence of methotrexate on the mortality of patients with rheumatoid arthritis is partly independent of its effect on disease activity: results of a re-evaluation 18 years after baseline. Clin Exp Rheumatol 32:395–400

    CAS  PubMed  Google Scholar 

  16. 16.

    Zochling J, Stucki G, Grill E, Braun J (2007) A comparative study of patient-reported functional outcomes in acute rheumatoid arthritis. J Rheumatol 34:64–69

    PubMed  Google Scholar 

  17. 17.

    Puolakka K, Kautiainen H, Möttönen T, FIN-RACo Trial Group et al (2005) 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 52:36–41

    Article  PubMed  Google Scholar 

  18. 18.

    Krause D, Gabriel B, Herborn G, Braun J, Rau R (2015) Radiologic damage at baseline predicts patient related outcomes 18 years after the initiation of methotrexate therapy in patients with severe rheumatoid arthritis. Clin Exp Rheumatol 33:611–616

    PubMed  Google Scholar 

  19. 19.

    Combe B, Cantagrel A, Goupille P et al (2003) Predictive factors of 5-year health assessment questionnaire disability in early rheumatoid arthritis. J Rheumatol 30:2344–2349

    PubMed  Google Scholar 

  20. 20.

    van Nies JA, Krabben A, Schoones JW, Huizinga TW, Kloppenburg M, van der Helm-van Mil AH (2014) What is the evidence for the presence of a therapeutic window of opportunity in rheumatoid arthritis? A systematic literature review. Ann Rheum Dis 73:861–870

    Article  PubMed  Google Scholar 

  21. 21.

    Saevarsdottir S, Wallin H, Seddighzadeh M, Ernestam S, Geborek P, Petersson IF, Bratt J, van Vollenhoven RF, SWEFOT Trial Investigators Group (2011) Predictors of response to methotrexate in early DMARD naive rheumatoid arthritis: results from the initial open-label phase of the SWEFOT trial. Ann Rheum Dis 70:469–475

    Article  PubMed  Google Scholar 

  22. 22.

    Zhu H, Deng FY, Mo XB, Qiu YH, Lei SF (2014) Pharmacogenetics and pharmacogenomics for rheumatoid arthritis responsiveness to methotrexate treatment: the 2013 update. Pharmacogenomics 15:551–566

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Fransen J, Kooloos WM, Wessels JA, Huizinga TW, Guchelaar HJ, van Riel PL, Barrera P (2012) Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure. Pharmacogenomics 13:1087–1094

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Brinker RR, Ranganathan P (2010) Methotrexate pharmacogenetics in rheumatoid arthritis. Clin Exp Rheumatol 28(Suppl 61):33–39

    Google Scholar 

  25. 25.

    Wessels JA, de Vries-Bouwstra JK, Heijmans BT et al (2006) Efficacy und toxicity of methotrexate in early rheumatoid arthritis are associated with single-nucleotide polymorphisms in genes coding for folate pathway enzymes. Arthritis Rheum 54:1087–1095

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Kato T, Hamada A, Mori S, Saito H (2012) Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact clinical outcome of methotrexate monotherapy in Japanese patients with rheumatoid arthritis. Drug Metab Pharmacokinet 27:192–199

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, Kremer J (2004) Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 50:2766–2774

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Ponchel F, Goëb V, Parmar R et al (2014) An immunological biomarker to predict MTX response in early RA. Ann Rheum Dis 73:2047–2053

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Dietmar Krause.

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Krause, D., Gabriel, B., Herborn, G. et al. Response to methotrexate predicts long-term patient-related outcomes in rheumatoid arthritis. Clin Rheumatol 35, 1123–1127 (2016). https://doi.org/10.1007/s10067-016-3216-y

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Keywords

  • Long term follow-up
  • Methotrexate
  • Patient outcome assessment
  • Rheumatoid arthritis