Skip to main content

Advertisement

SpringerLink
Log in

Effects of long-term corticosteroid usage on functional disability in patients with early rheumatoid arthritis, regardless of controlled disease activity

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

We investigated the effect of long-term corticosteroid usage in suppressing the progression of functional disability in patients with early rheumatoid arthritis (RA). We studied 3,982 RA patients, who had continuous enrollment for at least 3 years, among 9,132 RA patients enrolled in an observational cohort study, IORRA, in Tokyo, Japan, from 2000 to 2007. The DAS28 and Japanese version of Health Assessment Questionnaire (J-HAQ) scores were collected at 6-month intervals (each phase). Among these patients, those with DAS28 values under 3.2 in all phases and RA disease duration under 2 years at study entry were selected as “early RA patients with well-controlled disease”. These patients were further classified into 3 groups based on average months of steroid usage per year: Non-users, Medium-users, and Frequent-users. Multiple linear regression analysis was used to study the relationship between steroid usage and the final J-HAQ scores. Among the 3,982 patients, 109 had DAS28 values under 3.2 in all the phases and were selected as study cohort. The average Final J-HAQ in Non-user (N = 64), in Medium-user (N = 25), in Frequent-user group (N = 20) was 0.04, 0.06, and 0.33, respectively. Multiple linear regression analysis after adjusting for all potential covariates confirmed that frequent steroid usage was the most significant factor associated with higher final J-HAQ scores (P < 0.05). Frequent steroid usage was associated with significantly higher final J-HAQ scores in early RA patients, even though their disease was managed efficiently by maintaining the DAS28 values under 3.2 over a long-term period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Weaver AL (2004) The impact of new biologicals in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 43(suppl 3): iii17–iii23

    Google Scholar 

  2. Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW et al. (2005) Updated consensus statement on biological agents, specifically tumor necrosis factor {alpha} (TNF{alpha}) blocking agents and interleukin-1 receptor antagonist (IL-1ra), for the treatment of rheumatic diseases. Ann Rheum Dis 64(suppl 4): iv2–iv14

    Google Scholar 

  3. Albers JM, Paimela L, Kurki P, Eberhardt KB, Emery P, van ‘t Hof MA et al (2001) Treatment strategy, disease activity, and outcome in four cohorts of patients with early rheumatoid arthritis. Ann Rheum Dis 60:453–458

    Article  PubMed  CAS  Google Scholar 

  4. van Aken J, Lard LR, le Cessie S, Hazes JM, Breedveld FC, Huizinga TW (2004) Radiological outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis 63:274–279

    Article  PubMed  Google Scholar 

  5. Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS (2004) Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 43:906–914

    Article  CAS  Google Scholar 

  6. Pincus T, Marcum SB, Callahan LF (1992) Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 19:1885–1894

    PubMed  CAS  Google Scholar 

  7. Solomon DH, Katz JN, Jacobs JP, La Tourette AM, Coblyn J (2002) Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice. Arthritis Rheum 46:3136–3142

    Article  PubMed  Google Scholar 

  8. Moreland LW, O’Dell JR (2002) Glucocorticoids and rheumatoid arthritis: back to the future? Arthritis Rheum 46:2553–2563

    Article  PubMed  CAS  Google Scholar 

  9. Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A et al (1999) Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Lancet 353:259–266

    Article  PubMed  CAS  Google Scholar 

  10. Tugwell P, Pincus T, Yocum D, Stein M, Gluck O, Kraag G et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The methotrexate-cyclosporine combination study group. N Engl J Med 333:137–141

    Article  PubMed  CAS  Google Scholar 

  11. O’Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334:1287–1291

    Article  PubMed  Google Scholar 

  12. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D, Macfarlane JD et al (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 41:1552–1563

    Article  PubMed  CAS  Google Scholar 

  13. Weinblatt ME, Kremer JM, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Fox RI et al (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340:253–259

    Article  PubMed  CAS  Google Scholar 

  14. Lipsky PE, van der Heijde DM, St Clair EW, Furst DE, Breedveld FC, Kalden JR et al (2000) 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 343:1594–1602

    Article  PubMed  CAS  Google Scholar 

  15. Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW et al (2002) Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46:614–624

    Article  PubMed  CAS  Google Scholar 

  16. Kalla AA, Tikly M (2003) Rheumatoid arthritis in the developing world. Best Pract Res Clin Rheumatol 17:863–875

    Article  PubMed  Google Scholar 

  17. Kirwan JR (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The arthritis and rheumatism council low-dose glucocorticoid study group. N Engl J Med 333:142–146

    Article  PubMed  CAS  Google Scholar 

  18. Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC et al (1997) Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 350:309–318

    Article  PubMed  CAS  Google Scholar 

  19. van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW (2002) Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 136:1–12

    PubMed  Google Scholar 

  20. Hickling P, Jacoby RK, Kirwan JR (1998) Joint destruction after glucocorticoids are withdrawn in early rheumatoid arthritis. Arthritis and rheumatism council low dose glucocorticoid study group. Br J Rheumatol 37:930–936

    Article  PubMed  CAS  Google Scholar 

  21. Wassenberg S, Rau R, Steinfeld P, Zeidler H (2005) Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 52:3371–3380

    Article  PubMed  CAS  Google Scholar 

  22. Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafstrom I (2005) Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial. Arthritis Rheum 52:3360–3370

    Article  PubMed  CAS  Google Scholar 

  23. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM et al (2005) Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 52:3381–3390

    Article  PubMed  CAS  Google Scholar 

  24. Kirwan JR, Bijlsma JWJ, Boers M, Shea BJ (2007) Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database Rev 1:CD006356

  25. Criswell LA, Saag KG, Sems KM, Robinson V, Shea B, Wells G, Suarez-Almazor ME (1998) Moderate-term, low-dose corticosteroids for rheumatoid arthritis. Cochrane Database Rev 3:CD001158

    Google Scholar 

  26. Gøtzsche PC, Johansen HK (2005) Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Cochrane Database Rev 1:CD000189

  27. Saag KG, Criswell LA, Sems KM, Nettleman MD, Kolluri S (1996) Low-dose corticosteroids in rheumatoid arthritis. A meta-analysis of their moderate-term effectiveness. Arthritis Rheum 39:1818–1825

    Article  PubMed  CAS  Google Scholar 

  28. Gotzsche PC, Johansen HK (1998) Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ 316:811–818

    Article  PubMed  CAS  Google Scholar 

  29. Paulus HE, Di Primeo D, Sanda M, Lynch JM, Schwartz BA, Sharp JT et al (2000) Progression of radiographic joint erosion during low dose corticosteroid treatment of rheumatoid arthritis. J Rheumatol 27:1632–1637

    PubMed  CAS  Google Scholar 

  30. Hansen M, Podenphant J, Florescu A, Stoltenberg M, Borch A, Kluger E et al (1999) A randomised trial of differentiated prednisolone treatment in active rheumatoid arthritis. Clinical benefits and skeletal side effects. Ann Rheum Dis 58:713–718

    Article  PubMed  CAS  Google Scholar 

  31. Capell HA, Madhok R, Hunter JA, Porter D, Morrison E, Larkin J et al (2004) Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis 63:797–803

    Article  PubMed  CAS  Google Scholar 

  32. Iikuni N, Inoue E, Tanaka E, Hara M, Tomatsu T, Kamatani N et al (2008) Low disease activity state with corticosteroid may not represent ‘true’ low disease activity state in patients with rheumatoid arthritis. Rheumatology (Oxford) 47:519–521

    Article  CAS  Google Scholar 

  33. Yamanaka H, Tohma S (2006) Potential impact of observational cohort studies in Japan on rheumatoid arthritis research and practice. Mod Rheumatol 16:75–76

    Article  PubMed  Google Scholar 

  34. Matsuda Y, Singh G, Yamanaka H, Tanaka E, Urano W, Taniguchi A et al (2003) Validation of a Japanese version of the Stanford Health Assessment Questionnaire in 3,763 patients with rheumatoid arthritis. Arthritis Rheum 49:784–788

    Article  PubMed  Google Scholar 

  35. Tanaka E, Saito A, Kamitsuji S, Yamada T, Nakajima A, Taniguchi A et al (2005) Impact of shoulder, elbow, and knee joint involvement on assessment of rheumatoid arthritis using the American College of rheumatology core data set. Arthritis Rheum 53:864–871

    Article  PubMed  Google Scholar 

  36. Furuya T, Kotake S, Inoue E, Nanke Y, Yago T, Kobashigawa T et al (2007) Risk factors associated with incident clinical vertebral and nonvertebral fractures in Japanese women with rheumatoid arthritis: a prospective 54-month observational study. J Rheumatol 34:303–310

    PubMed  Google Scholar 

  37. Yamanaka H, Inoue E, Singh G, Tanaka E, Nakajima A, Taniguchi A et al (2007) Improvement of disease activity of rheumatoid arthritis patients from 2000 to 2006 in a large observational cohort study IORRA in Japan. Mod Rheumatol 17:283–289

    Article  PubMed  Google Scholar 

  38. Nakajima A, Kamitsuji S, Saito A, Tanaka E, Nishimura K, Horikawa N et al (2006) Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan. Mod Rheumatol 16:151–157

    Article  PubMed  Google Scholar 

  39. Yamada T, Nakajima A, Inoue E, Tanaka E, Hara M, Tomatsu T et al (2006) Increased risk of tuberculosis in patients with rheumatoid arthritis in Japan. Ann Rheum Dis 65:1661–1663

    Article  PubMed  CAS  Google Scholar 

  40. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1998) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  Google Scholar 

  41. van der Heijde DM, van ‘t Hof MA, van Riel PL, Theunisse LA, Lubberts EW, van Leeuwen MA et al. (1990) Judging disease activity in clinical practice in rheumatoid arthritis: first step in the development of a disease activity score. Ann Rheum Dis 49:916–920

    Google Scholar 

  42. Prevoo ML, van ‘t Hof MA, 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 38:44–48

    Google Scholar 

  43. Iikuni N, Nakajima A, Inoue E, Tanaka E, Okamoto H, Hara M et al (2007) What’s in season for rheumatoid arthritis patients? Seasonal fluctuations in disease activity. Rheumatology (Oxford) 46:846–848

    Article  CAS  Google Scholar 

  44. Drossaers-Bakker KW, de Buck M, van Zeben D, Zwinderman AH, Breedveld FC, Hazes JM (1999) Long-term course and outcome of functional capacity in rheumatoid arthritis: the effect of disease activity and radiologic damage over time. Arthritis Rheum 42:1854–1860

    Article  PubMed  CAS  Google Scholar 

  45. Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL (2001) The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum 44:2009–2017

    Article  PubMed  CAS  Google Scholar 

  46. Guillemin F, Briancon S, Pourel J (1992) Functional disability in rheumatoid arthritis: two different models in early and established disease. J Rheumatol 19:366–369

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  48. Jansen LM, van Schaardenburg D, van Der Horst-Bruinsma IE, Bezemer PD, Dijkmans BA (2000) Predictors of functional status in patients with early rheumatoid arthritis. Ann Rheum Dis 59:223–226

    Article  PubMed  CAS  Google Scholar 

  49. Guillemin F, Suurmeijer T, Krol B, Bombardier C, Briancon S, Doeglas D et al (1994) Functional disability in early rheumatoid arthritis: description and risk factors. J Rheumatol 21:1051–1055

    PubMed  CAS  Google Scholar 

  50. van der Heijde DM, van’t Hof MA, van Riel PL, van Leeuwen MA, van Rijswijk MH, van de Putte LB (1992) Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis. Ann Rheum Dis 51:177–181

    Google Scholar 

  51. Smedstad LM, Kvien TK, Moum T, Vaglum P (1995) Life events, psychosocial factors, and demographic variables in early rheumatoid arthritis: relations to one-year changes in functional disability. J Rheumatol 22:2218–2225

    PubMed  CAS  Google Scholar 

  52. Uhlig T, Smedstad LM, Vaglum P, Moum T, Gerard N, Kvien TK (2000) The course of rheumatoid arthritis and predictors of psychological, physical and radiographic outcome after 5 years of follow-up. Rheumatology (Oxford) 39:732–741

    Article  CAS  Google Scholar 

  53. Townsend HB, Saag KG (2004) Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms, and risks. Clin Exp Rheumatol 22:S77–S82

    PubMed  CAS  Google Scholar 

  54. Bijlsma JW, Hoes JN, Van Everdingen AA, Verstappen SM, Jacobs JW (2006) Are glucocorticoids DMARDs? Ann N Y Acad Sci 1069:268–274

    Article  PubMed  CAS  Google Scholar 

  55. Bijlsma JW, Van Everdingen AA, Huisman M, De Nijs RN, Jacobs JW (2002) Glucocorticoids in rheumatoid arthritis: effects on erosions and bone. Ann N Y Acad Sci 966:82–90

    Article  PubMed  CAS  Google Scholar 

  56. Guidelines for the management of rheumatoid arthritis (2002) 2002 Update. American College of rheumatology subcommittee on rheumatoid arthritis guidelines. Arthritis Rheum 46:328–346

    Article  Google Scholar 

  57. van Gestel AM, Haagsma CJ, van Riel PL (1998) Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 41:1845–1850

    Article  PubMed  Google Scholar 

  58. Makinen H, Kautiainen H, Hannonen P, Mottonen T, Leirisalo-Repo M, Laasonen L et al (2007) Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis. J Rheumatol 34:316–321

    PubMed  CAS  Google Scholar 

  59. Pincus T, Yazici Y, Bergman M, Swearingen C, Harrington T (2006) A proposed approach to recognise “near-remission” quantitatively without formal joint counts or laboratory tests: a patient self-report questionnaire routine assessment of patient index data (RAPID) score as a guide to a “continuous quality improvement” s. Clin Exp Rheumatol 24:S060–S073

    Google Scholar 

  60. Fransen J, Moens HB, Speyer I, van Riel PL (2005) Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised controlled trial. Ann Rheum Dis 64:1294–1298

    Article  PubMed  CAS  Google Scholar 

  61. Lambert CM, Sandhu S, Lochhead A, Hurst NP, McRorie E, Dhillon V (2004) Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomized, controlled trial. Arthritis Rheum 50:364–371

    Article  PubMed  CAS  Google Scholar 

  62. Fransen J, Creemers MC, Van Riel PL (2004) Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology (Oxford) 43:1252–1255

    Article  CAS  Google Scholar 

  63. van Riel PL, van Gestel AM (2000) Clinical outcome measures in rheumatoid arthritis. Ann Rheum Dis 59(suppl 1):i28–i31

    Google Scholar 

  64. Sesin CA, Bingham CO (2005) Remission in rheumatoid arthritis: wishful thinking or clinical reality? Semin Arthritis Rheum 35:185–196

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  66. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM (1995) Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoid arthritis. J Rheumatol 22:1055–1059

    PubMed  CAS  Google Scholar 

  67. McDougall R, Sibley J, Haga M, Russell A (1994) Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched controls. J Rheumatol 21:1207–1213

    PubMed  CAS  Google Scholar 

  68. Saag KG, Koehnke R, Caldwell JR, Brasington R, Burmeister LF, Zimmerman B et al (1994) Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 96:115–123

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank all members of the Institute of Rheumatology, Tokyo Women’s Medical University, for the successful management of the IORRA cohort. The IORRA cohort is supported by a consortium of 38 pharmaceutical companies, and Institute of Clinical Outcome Research and Education (ICORE) received grant support from Centocor Inc. for research in this area. The authors also would like to thank supports by Banyu Life Science Foundation International and Japan Rheumatism Foundation.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA

    Eiichi Tanaka, Ajitha Mannalithara & Gurkirpal Singh

  2. Institute of Clinical Outcomes Research and Education, Palo Alto, CA, USA

    Eiichi Tanaka, Ajitha Mannalithara & Gurkirpal Singh

  3. Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan

    Eiichi Tanaka, Eisuke Inoue, Noriko Iikuni, Atsuo Taniguchi, Shigeki Momohara & Hisashi Yamanaka

Authors
  1. Eiichi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ajitha Mannalithara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eisuke Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Noriko Iikuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Atsuo Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shigeki Momohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gurkirpal Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hisashi Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eiichi Tanaka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanaka, E., Mannalithara, A., Inoue, E. et al. Effects of long-term corticosteroid usage on functional disability in patients with early rheumatoid arthritis, regardless of controlled disease activity. Rheumatol Int 32, 749–757 (2012). https://doi.org/10.1007/s00296-010-1638-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1638-4

Keywords

Search

Navigation