Skip to main content

Advertisement

Log in

Update on the medical treatment of juvenile idiopathic arthritis

  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Hashkes PJ, Laxer RM: Medical treatment of juvenile idiopathic arthritis. JAMA 2005, 294:1671–1684. The first paper to suggest evidence-based guidelines for the treatment of the various subtypes of JIA based on a 39-year evidence-based systematic literature review.

    Article  PubMed  CAS  Google Scholar 

  2. Giannini EH, Ruperto N, Ravelli A, et al.: Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997, 40:1202–1209.

    PubMed  CAS  Google Scholar 

  3. Wallace CA, Ruperto N, Giannini E, et al.: Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004, 31:2290–2294.

    PubMed  Google Scholar 

  4. Wallace CA, Huang B, Bandeira M, et al.: Patterns of clinical remission in select categories of juvenile idiopathic arthritis. Arthritis Rheum 2005, 52:3554–3562. This study examined the longevity of remission of patients with JIA with and without medication. Only a small minority of patients was able to attain more than a 5-year remission without medication. New treatment regimens are necessary to increase long-term remission rates.

    Article  PubMed  Google Scholar 

  5. van Rossum MA, Boers M, Zwinderman AH, et al.: Development of a standardized method of assessment of radiographs and radiographic changes in juvenile idiopathic arthritis: introduction of the Dijkstra composite score. Arthritis Rheum 2005, 52:2865–2872. The first comprehensive scale developed to assess radiologic damage in JIA, which may serve as a model for clinical trials and long-term outcome studies.

    Article  PubMed  Google Scholar 

  6. van Rossum MA, Fiselier TJ, Franssen MJ, et al.: Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized double-blind placebo-controlled, multicenter study. Arthritis Rheum 1998, 41:808–816.

    Article  PubMed  Google Scholar 

  7. Viola S, Felici E, Magni-Manzoni S, et al.: Development and validation of a clinical index for assessment of long-term damage in juvenile idiopathic arthritis. Arthritis Rheum 2005, 52:2092–2102. This group developed and validated an easy to apply and score articular and extra-articular damage index.

    Article  PubMed  Google Scholar 

  8. Magni-Manzoni S, Solari N, Palmisani E, et al.: Towards the developement of a disease activity score for juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2005, 52(Suppl):S89–90.

    Google Scholar 

  9. Brown GT, Wright FV, Lang BA, et al.: Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections. Arthritis Rheum 2005, 53:897–904.

    Article  PubMed  Google Scholar 

  10. Ruperto N, Nikishina I, Pachanov ED, et al.: A randomized double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results. Arthritis Rheum 2005, 52:563–572. Controlled trial showing that meloxicam was equivalent to naproxen with a similar safety profile. It was one of the few trials to monitor NSAIDs adverse effects for more than 6 months.

    Article  PubMed  CAS  Google Scholar 

  11. Gedalia A, Espada G, Johnson P, et al.: Efficacy and safety of meloxicam oral suspension in the treatment of juvenile rheumatoid arthritis (JRA): results from a twelve-week active-controlled (naproxen oral suspension), multinational trial [abstract]. Arthritis Rheum 2004, 50(Suppl):S95.

    Google Scholar 

  12. Kiss MH, Reiff AA, Reicin AS, et al.: Rofecoxib demonstrates efficacy and tolerability in children and adolescents (ages 2–17 years) with juvenile rheumatoid arthritis (JRA) in a 12-week randomized study [abstract]. Arthritis Rheum 2003, 48(Suppl):S650.

    Google Scholar 

  13. Rapoff MA, Belmont JM, Lindsley CB, Olson NY: Electronically monitored adherence to medications by newly diagnosed patients with juvenile rheumatoid arthritis. Arthritis Rheum 2005, 53:905–910.

    Article  PubMed  Google Scholar 

  14. Zulian F, Martini G, Gobber D, et al.: Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a doubleblind trial. Rheumatology 2004, 43:1288–1291. Elegant study examining the results of joint injections of paired inflamed joints and demonstrating the superiority of triamcinolone hexacetonide to triamcinolone acetonide.

    Article  PubMed  CAS  Google Scholar 

  15. Eberhard BA, Sison MC, Gottlieb BS, Ilowite NT: Comparison of the intraarticular effectiveness of triamcinolone hexacetonide and triamcinolone acetonide in treatment of juvenile rheumatoid arthritis. J Rheumatol 2004, 31:2507–2512.

    PubMed  CAS  Google Scholar 

  16. Eberhard BA, Sison MC, Gottlieb BS, Ilowite NT: Dose for intra-articular steroids: is more really better [abstract]? Arthritis Rheum 2005, 52(Suppl):S83.

    Google Scholar 

  17. Arabshahi B, Dewitt EM, Cahill AM, et al.: Utility of corticosteroid injection for temporomandibular arthritis in children with juvenile idiopathic arthritis. Arthritis Rheum 2005, 52:3563–3569. This study demonstrated the effect of steroid injections in arthritis of the TMJ and will assist in convincing oral surgeons to perform this procedure.

    Article  PubMed  CAS  Google Scholar 

  18. Nicheus T, Horneff G, Michels H, et al.: Evidence-based use of methotrexate in children with rheumatic diseases: a consensus statement of the Working Groups Pediatric Rheumatology Germany (AGKJR) and Pediatric Rheumatology Austria. Rheumatol Int 2005, 25:169–178.

    Article  Google Scholar 

  19. Ruperto N, Murray KJ, Gerloni V, et al.: A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum 2004, 50:2191–2201. This very large controlled trial showed that the majority of patients not responsive to an oral dose of methotrexate at 10 mg/m2 benefit from an increase in the dose to 15 mg/m2, given parenterally. No additional benefit was found in further increasing the dose of methotrexate.

    Article  PubMed  CAS  Google Scholar 

  20. Alsufyani K, Ortiz-Alvarez O, Cabral DA, et al.: The role of subcutaneous administration of methotrexate in children with juvenile idiopathic arthritis who have failed oral methotrexate. J Rheumatol 2004, 31:179–182.

    PubMed  CAS  Google Scholar 

  21. Brik R, Gepstein V, Berkovitz D: Low dose methotrexate treatment for oligoarticular juvenile idiopathic arthritis nonresponsive to intra-articular corticosteroids. Clin Rheumatol 2005, 24:612–614.

    Article  PubMed  Google Scholar 

  22. Schmeling H, Biber D, Heins S, Horneff G: Influence of methylenetetrahydrofolate reductase polymorphisms on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis. J Rheumatol 2005, 32:1832–1836. The first study to examine the influence of genetics on the efficacy and toxicity of methotrexate in JIA.

    PubMed  CAS  Google Scholar 

  23. Dolezalova P, Krijt J, Chladek J, et al.: Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis. Rheumatology (Oxford) 2005, 44:74–79.

    Article  CAS  Google Scholar 

  24. Chedeville G, Quartier P, Miranda M, et al.: Improvements in growth parameters in children with juvenile idiopathic arthritis associated with the effect of methotrexate on disease activity. Joint Bone Spine 2005, 72:392–396.

    Article  PubMed  Google Scholar 

  25. Foell D, Frosch M, Schulze zur Wiesch A, et al.: Methotrexate treatment in juvenile idiopathic arthritis: when is the right time to stop? Ann Rheum Dis 2004, 63:206–208.

    Article  PubMed  CAS  Google Scholar 

  26. Ortiz-Alvarez O, Morishita K, Avery G, et al.: Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis. J Rheumatol 2004, 31:2501–2506.

    PubMed  CAS  Google Scholar 

  27. van Rossum MA, van Soesbergen RM, Zwinderman AH, et al.: Long-term outcome of juvenile idiopathic arthritis following a placebo-controlled trial: sustained benefits of early sulfasalazine treatment [abstract]. Arthritis Rheum 2005, 52(Suppl):S86. This study showed that early aggressive therapy may have a positive effect on the course of JIA long after the drug was discontinued.

    Google Scholar 

  28. Silverman E, Mouy R, Spiegel L, et al.: Leflunomide or methotrexate for juvenile rheumatoid arthritis. New Engl J Med 2005, 352:1655–1666. This controlled study showed that methotrexate is superior to leflunomide, especially in younger patients given a leflunomide dose of 10 mg every other day. However, leflunomide may serve as an alternative to methotrexate in patients not responsive or intolerant of methotrexate.

    Article  PubMed  CAS  Google Scholar 

  29. Shi J, Kovacs SJ, Wang Y, et al.: Population pharmacokinetics of the active metabolite of leflunomide in pediatric subjects with polyarticular course juvenile rheumatoid arthritis. J Pharmackinet Pharmacodyn 2005, 32:419–439.

    Article  CAS  Google Scholar 

  30. Silverman E, Spiegel L, Hawkins D, et al.: Long-term open-label preliminary study of the safety and efficacy of leflunomide in patients with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2005, 52:554–562.

    Article  PubMed  CAS  Google Scholar 

  31. Lehman TJ, Schechter SJ, Sundel RP, et al.: Thalidomide for severe systemic onset juvenile rheumatoid arthritis. J Pediatr 2004, 145:856–857.

    Article  PubMed  CAS  Google Scholar 

  32. Badot V, Debandt M, Deslandre CJ, et al.: Efficacy and tolerance of thalidomide in refractory systemic onset juvenile idiopathic arthritis: a retrospective study in 19 patients [abstract]. Arthritis Rheum 2005, 52(Suppl):S85.

    Google Scholar 

  33. Lovell DJ, Giannini EH, Reiff A, et al.: Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med 2000, 342:763–769.

    Article  PubMed  CAS  Google Scholar 

  34. Lovell D, Reiff A, Jones OY, et al.: Long-term safety and efficacy experience with etanercept (Enbrel) in children with polyarticular juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2004, 50(Suppl):S436.

    Google Scholar 

  35. Horneff G, Schmeling H, Biedermann T, et al.: The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004, 63:1638–1644.

    Article  PubMed  CAS  Google Scholar 

  36. Quartier P, Taupin P, Bourdeaut F, et al.: Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 2003, 48:1093–1101.

    Article  PubMed  CAS  Google Scholar 

  37. Kimura Y, Pinho P, Walco G, et al.: Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 2005, 32:935–942.

    PubMed  CAS  Google Scholar 

  38. Horneff G, Girschick H, Michels H, et al.: Factors associated with failure of etanercept therapy in systemic onset juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2004, 50(Suppl):S93.

    Google Scholar 

  39. Horneff G, Schmeling H, Moebius D, Foeldvari I: Efficacy of etanercept in active refractory juvenile spondyloarthropathy: prospective open study of 40 patients [abstract]. Arthritis Rheum 2004, 50(Suppl):S91.

    Google Scholar 

  40. Henrickson M, Reiff A: Prolonged efficacy of etanercept in refractory enthesitis-related arthritis. J Rheumatol 2004, 31:2055–2061.

    PubMed  CAS  Google Scholar 

  41. Tse SM, Burgos-Vargas R, Laxer RM: Anti-tumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthropathy. Arthritis Rheum 2005, 52:2103–2108.

    Article  PubMed  CAS  Google Scholar 

  42. Horneff G, Girschick H, Foeldvari I, et al.: Combination therapy with etanercept and methotrexate compared to etanercept monotherapy in patients with juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2005, 52(Suppl):S724-S725.

    Google Scholar 

  43. Yim DS, Zhou H, Buckwalter M, et al.: Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis. J Clin Pharmacol 2005, 45:246–256.

    Article  PubMed  CAS  Google Scholar 

  44. Lovell DJ, Ruperto N, Cuttica R, et al.: Comparison of safety, efficacy and pharmacokinetics for 3 and 6 mg/kg infliximab plus methotrexate in JRA patients [abstract]. Arthritis Rheum 2005, 52(Suppl):S724. Although still published only as an abstract, this controlled study compared infliximab to placebo for polyarthritis and showed the better safety profile of a 6 mg/kg dose as opposed to 3 mg/kg.

    Google Scholar 

  45. Gerloni V, Pontikaki I, Gattinara M, et al.: Efficacy of repeated intravenous infusions of an anti-tumor necrosis factor alpha monoclonal antibody, infliximab, in persistent active, refractory juvenile idiopathic arthritis. Results of an open-label prospective study. Arthritis Rheum 2005, 52:548–553.

    Article  PubMed  CAS  Google Scholar 

  46. Katsicas MM, Russo RA: Use of infliximab in patients with systemic juvenile idiopathic arthritis refractory to etanercept. Clin Exp Rheumatol 2005, 23:545–548.

    PubMed  CAS  Google Scholar 

  47. Lovell DJ, Ruperto N, Goodman S, et al.: Preliminary data from the study of adalimumab in children with juvenile idiopathic arthritis (JIA) [abstract]. Arthritis Rheum 2004, 50(Suppl):S436.

    Google Scholar 

  48. Armbrust W, Kamphuis SS, Wolfs TW, et al.: Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 2004, 43:527–529.

    Article  CAS  Google Scholar 

  49. Lepore L, Marchetti F, Facchini S, et al.: Drug-induced systemic lupus erythematosus associated with etanercept therapy in a child with juvenile idiopathic arthritis. Clin Exp Rheumatol 2003, 21:276–277.

    PubMed  CAS  Google Scholar 

  50. Southwood TR, Cummins CL, Foster HE, et al.: Adverse events in juvenile idiopathic arthritis patients treated with etanercept of the combination of etanercept and methotrexate [abstract]. Arthritis Rheum 2005, 52(Suppl):S84. This abstract, which found more adverse effects of combined therapy as opposed to monotherapy, demonstrated the need for a formal study of combined therapy in JIA.

    Google Scholar 

  51. Nielsen S, Ruperto N, Simonini G, et al.: Preliminary evidence that etanercept is more effective than methotrexate in suppressing inflammation and in reducing radiographic progression in juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2005, 52(Suppl):S82-S83.

    Google Scholar 

  52. Simonini G, Giani T, Stagi S, et al.: Bone status over 1 year of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford) 2005, 44:777–780.

    Article  CAS  Google Scholar 

  53. Verbsky JW, White AJ: Effective use of recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 2004, 31:201–205.

    Google Scholar 

  54. Irigoyen PI, Olson J, Hom C, Ilowite NT: Treatment of systemic onset juvenile rheumatoid arthritis with anakinra [abstract]. Arthritis Rheum 2004, 50(Suppl):S437.

    Google Scholar 

  55. Weiss J, Henrickson M, Walco G, et al.: Combination therapy with anakinra and anti-TNF agents in refractory systemic JIA [abstract]. Arthritis Rheum 2005, 52(Suppl):S84-S85.

    Google Scholar 

  56. Pascual V, Allantaz F, Arce E, et al.: Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005, 201:1479–1486. This study showed the molecular rational and clinical benefit of IL-1 antagonism in systemic arthritis.

    Article  PubMed  CAS  Google Scholar 

  57. Yokota S, Miyamae T, Imagawa T, et al.: Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2005, 52:818–825.

    Article  PubMed  CAS  Google Scholar 

  58. Woo P, Wilkinson N, Prieur AM, et al.: Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 2005, 7:R1281-R1288.

    Article  PubMed  CAS  Google Scholar 

  59. De Kleer IM, Brinkman DM, Ferster A, et al.: Autologous stem cell transplantation for refractory juvenile idiopathic arthritis: analysis of clinical effects, mortality, and transplant related morbidity. Ann Rheum Dis 2004, 63:1318–1326.

    Article  Google Scholar 

  60. Wulffraat NM, Vastert B, Tyndall A: Treatment of refractory autoimmune diseases with autologous stem cell transplantation: focus on juvenile idiopathic arthritis. Bone Marrow Transplant 2005, 35(Suppl 1):S27-S29.

    Article  PubMed  Google Scholar 

  61. Mier R, Brunner H, Rosenberg A, Wallace C: Diagnostic predictors of poor outcome of uveitis associated with juvenile idiopathic arthritis [abstract]. Arthritis Rheum 2005, 52(Suppl):S88.

    Google Scholar 

  62. Foeldvari I, Wierk A: Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2005, 32:362–365.

    PubMed  CAS  Google Scholar 

  63. Yu EN, Meniconi ME, Tufail F, et al.: Outcomes of treatment with immunomodulatory therapy in patients with corticosteroid-resistant juvenile idiopathic arthritis-associated chronic iridocyclitis. Ocul Immunol Inflamm 2005, 13:353–360.

    Article  PubMed  CAS  Google Scholar 

  64. Malik AR, Pavesio C: The use of low dose methotrexate in children with chronic anterior and intermediate uveitis. Br J Ophthalmol 2005, 89:806–808.

    Article  PubMed  CAS  Google Scholar 

  65. Smith JA, Thompson DJ, Whitcup SM, et al.: A randomized, placebo-controlled double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum 2005, 53:18–23. This small, controlled study showed that etanercept is not the optimal biologic-modifying drug for JIA-associated uveitis.

    Article  PubMed  CAS  Google Scholar 

  66. Schmeling H, Horneff G: Etanercept and uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford) 2005, 44:1008–1011.

    Article  CAS  Google Scholar 

  67. Richards JC, Tay-Kearney ML, Murray K, Manners P: Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol 2005, 33:461–468.

    Article  Google Scholar 

  68. Rajaraman RT, Kimura Y, Li S, et al.: Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology 2006, 113:308–314.

    Article  PubMed  Google Scholar 

  69. Simonini G, Caputo R, De Libero C, et al.: Sustained improvement of refractory chronic uveitis on infliximab treatment [abstract]. Arthritis Rheum 2005, 52(Suppl):S86-S87.

    Google Scholar 

  70. Saurenmann RK, Levin AN, Rose JB, et al.: Tumor necrosis factor inhibitors in the treatment of childhood uveitis. Rheumatology 2006, 45:982–989.

    Article  PubMed  CAS  Google Scholar 

  71. Huber A, Tomlinson G, Koren G, Feldman BM: An innovative method to assess pain relief by amitriptyline in juvenile rheumatoid arthritis [abstract]. Arthritis Rheum 2005, 52(Suppl):S93.

    Google Scholar 

  72. Powell M, Seid M, Szer IS: Efficacy of custom foot orthotics in improving pain and functional status in children with juvenile idiopathic arthritis: a randomized trial. J Rheumatol 2005, 32:943–950. This is an example of a well-designed physical therapy trial. The results can help convince insurance companies to cover custommade foot orthotics for JIA patients with foot pain.

    PubMed  Google Scholar 

  73. Epps H, Ginnelly L, Utley M, et al.: Is hydrotherapy cost-effective? A randomized controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis. Health Tech Assess 2005, 9:39.

    Google Scholar 

  74. Saha MT, Haapasaari J, Hannula S, et al.: Growth hormone is effective in the treatment of severe growth retardation in children with juvenile chronic arthritis. Double blind placebocontrolled followup study. J Rheumatol 2004, 31:1413–1417. This controlled study showed the short-term benefit of growth hormone in severely growth retarded JIA patients, including those receiving corticosteroids.

    PubMed  CAS  Google Scholar 

  75. Gottlieb B, Sison C, Higgins G, et al.: Outcomes of juvenile rheumatoid arthritis (JRA): changing patterns and outcomes [abstract]. Arthritis Rheum 2005, 52(Suppl):S81-S82.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philip J. Hashkes MD, MSc.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hashkes, P.J., Laxer, R.M. Update on the medical treatment of juvenile idiopathic arthritis. Curr Rheumatol Rep 8, 450–458 (2006). https://doi.org/10.1007/s11926-006-0041-3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11926-006-0041-3

Keywords

Navigation