Treatment of juvenile idiopatic arthritis and biological agents

Abstract

Juvenile idiopathic arthritis (JIA) is the general term of a group of diseases including psoriatic arthritis and other spondyloarthropathies which are not in the spectrum of juvenile rheumatoid arthritis. Although up to date most of drugs are used for the treatment of this disease, an exact cure can not be developed. The targets of the therapy are protecting joint functions, improving clinic symptoms and providing achievement of normal growth and physical development. Disease modifiying antirheumatic drugs like methotrexate, sulfasalazine, hydroxychloroquine and corticosteroids, antiinflammatory agents are used for providing these targets. While the trials are going on about biologics related with rheumatic diseases, these agents are also being used for the treatment of JIA. In short and mid term periods promising results are validated from clinic trials. Three of these drugs, etanercept, adalimumab and abatacept are approved by FDA for the treatment of JIA. We are expecting long term results of ongoing trials with a great interest. 'Pediatric core set' related with the American College of Rheumatology (ACR) response levels are used for documentation of clinic results in research arena. New treatment researches are still going on bacause of there is no exact cure for this disease.

Keywords

• Juvenile idiopathic arthritis, disease modifiying antirheumatic drugs, anticytokine therapy

Jüvenil idyopatik artrtte tedavi biyolojik ajanlar

Abstract

Juvenil idyopatik artrit (JIA), psöriyatik artrit ve diğer spondiloartritler gibi hastalıkları da içine alan fakat juvenil romatoid artrit (JRA) spektrumu içinde bulunmayan hastalıklar grubunun genel adıdır. Geçmişten günümüze pek çok ajan kullanılmış olmakla beraber hastalığın kesin tedavisi sağlanamamıştır. Medikal tedavinin amaçları, eklem fonksiyonlarını korumak, semptomları iyileştirmek, normal büyüme ve gelişmenin devamını sağlamaktır. Bu amaçla metotreksat, sülfasalazin, hidroksiklorokin gibi temel etkili anti romatizmal ilaçlar, kortikosteroidler, non steroid anti enflamatuvar ilaçlar kullanılmıştır. Romatizmal hastalıkların tedavisinde biyolojik ajanların kullanımıyla birlikte bu ajanlar JIA tedavisinde de denenmiş, kısa ve orta vadede umut verici sonuçlar elde edilmiştir. Bu ajanlardan etanercept, adalimumab ve abatacept JIA tedavisinde Amerika Gıda ve İlaç Dairesi (FDA) tarafından onaylanmış üç ajandır. Bu ajanların JIA'de uzun vadeli sonuçları merakla beklenmektedir. Geliştirilmiş ajanların klinik etkilerinin araştırılmasında Amerikan Romatizma Cemiyeti'nin (ARC) cevap düzeylerinin değerlendirildiği 'core set data' denilen parametreler kullanılmaktadır. Hastalığın kesin tedavisinin olmaması nedeniyle yeni tedavi araştırmaları halen sürdürülmektedir.

Keywords

• Juvenil idyopatik artrit, temel etkili ajan, antisitokin tedavi

References

1. R.E. Petty, T.R. Southland, P. Manners, J. Baum, D.N. Glass and J. Goldenberg et al., International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis: second revision, Edmonton, 2001, J Rheumatol 2004; 31(2): 390–392.
2. Gartlehner G, Hansen R. Biologics for the treatment of juvenile idiopathic arthritis: a systematic review and critical analysis of the evidence. Clin Rheumatol. 2008; 27: 67-76.
3. Thompson SD, Moroldo MB, Guyer L. A genomewide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis Rheum. 2004; 50 (9): 2920–2930.
4. Butbul YA, Tyrrell PN, Schneider R, Dhillon S, Feldman BM, Laxer RM et al. Comparison of patients with juvenile psoriatic arthritis and nonpsoriatic juvenile idiopathic arthritis:how different are they? J. Rheumatol. 2009; 36(9): 1861-3.
5. J.E. Levinson and C.A. Wallace, Dismantling the pyramid, J Rheumatol Suppl 1992; 33: 6-10.
6. Takken T, Van der Net J, Helders PJ. Methotrexate for treating juvenile idiopathic arthritis. Cochrane Database Syst Rev 2001;(3):CD003129.
7. Carrasco R, Smith JA, Lovell D, Biologic agents for the treatment of juvenile rheumatoid arthritis: current status, Paediatr Drugs 2004; 6 (3): 137–146.
8. Wilkinson N, Jackson G, Gardner-Medwin J, Biologic therapies for juvenile arthritis, Arch Dis Child 2003; 88(3):186–191.

9. Otten MH, Prince FH, Ten Cate R, van Rossum MA, Twilt M, Hoppenreijs EP et al. Ann Rheum Dis. 2011; 70(2): 337-40.
10. Giannini EH, Ruperto N, Ravelli A. Preliminary definition of improvement in juvenile arthritis, Arthritis Rheum 1997; 40(7):1202– 1209.
11. Alarcaon GS. Methotrexate: ıts use for the treatment of rheumatoid arthritis and other rheumatic disorders. In Kopman WJ, ed. Arthritis and Allied Conditions. A textbook of rheumatology. Edition: 13th, Baltimore, Maryland, Williams&Wilkins, 1997. p.709-729.
12. Baggott JE, Morgan SL, Ha TS, Alarcon GS, Kopman WJ, Krumdieck CL: Antifolates in rheumatoid arthritis: a hypothetical mechanism of action. Clin. Exp. Rheumatol. 1993; 11(8): 101-105.
13. Cronstein BN, Naime D, Ostad E, The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation, J. Clin. Invest. 1993; 92 (6):2675–2682.
14. Segal R, Mozes E, Yaron M, Tartakovsky B: The effects of methotrexate on the production and activity of interleukin-1. Arthritis Rheum.1989; 32:370-377.
15. Sperling RI, Coblyn JS, Larkin JK, Benincaso Al, Austen KF, Weinblat ME: Inhibition of leukotriene B4 synthesis in neutrophils from patients with rheumatoid arthritis by a single oral dose of methotrexate. Arthritis Rheum. 1990; 33:1149-1155.
16. Wallace CA, The use of methotrexate in childhood rheumatic diseases, Arthritis Rheum. 1998;41: 381–391.
17. Alsufyani K, Ortiz-Alvarez O, Cabral D, 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.
18. Ravelli A, Migliavacca D and Viola S. Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis, Clin Exp Rheumatol. 1999; 17 (5):625–627.
19. Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract. Res. Clin Rheumatol. 2006; 20(2): 279-300.
20. Ruperto N, Murray KJ, Gerloni V, Wulffaat N, de Oliveira SK, Falcini F, 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;50:2191–201.
21. Laxer R, Gazarian M. Pharmacology and drug therapy. In: Cassidy J, Petty R, eds. Textbook of Pediatric Rheumatology. Philadelphia, PA: WB Saunders Co; 2001. p.110.
22. Van Rossum MA, Fiselier TJ and Franssen MJ, Zwinderman AH, ten Cate R, van Suijlekom-Smit LWA et al. Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Arthritis Group. Arthritis Rheum. 1998; 41(5): 808-16.
23. Van Rossum MA, Soesbergen RM, Boers M, Zwinderman AH, Fiselier JW, Franssen JAM et al. Long term outcome of juvenile idiopathic arthritis following a placebo controlled trial: sustained benefits of early sulfasalazine treatment. Ann Rheum Dis 2007; 66: 1518-1524.
24. Huang and L.C. Chen, Sulphasalazine in the treatment of children with chronic arthritis, Clin Rheumatol 1998;17 (5): 359–363.
25. Varbanova BB, Dyankov ED, Sulphasalazine. An alternative drug for second-line treatment of juvenile chronic arthritis, Adv in Exp Med Biol. 1999; 455:331–336.
26. Van Roon EN, Hoekstra M, Tobi H, Jansen TL, Bernelot Moens HJ, Brouwers JR et al. Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation. Br J Clin Pharmacol 2005; 60:319-325.
27. Kaltwasser JP, Behrens F. Leflunomide: Long-term clinical experience and new uses. Expert Opin Pharmacother 2005; 6: 787- 801.
28. Hayward K. Wallace CA. Recent developments in anti-rheumatic drugs in pediatrics: treatment of juvenile idiopathic arthritis. Arthritis Research Therapy. 2009; 11:216.
29. Brewer EJ, Giannini EH, Kuzmina N, Alekseev L. Penicillamine and hydroxychloroquine in the treatment of severe juvenile rheumatoid arthritis. Results of the USA–USSR double-blind placebo-controlled trial, N Engl J Med. 1986; 314 (20):1269–1276.
30. C. van Kerckhove, Giannini EH, Lovell DJ Temporal patterns of response to D-penicillamine, hydroxychloroquine, and placebo in juvenile rheumatoid arthritis patients. Arthritis Rheum. 1988;31 (10):1252–1258.
31. Shenoi S, Wallace CA. Tumor necrosis factor inhibitors in the management of juvenile idiopathic arthritis: an evidence based review. Paediatr Drugs. 2010; 12(6): 367-77.
32. Mease PJ, Goffe BS, Metz J, Vanderstoep A, Finck B, Burge DS et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomized trial, Lancet 2000; 356:385–390.
33. Straub RH , Härle P and P. Sarzi-Puttini. Tumor necrosis factor- neutralizing therapies improve altered hormone axes: An alternative mode of anti-inflammatory action, Arthritis Rheum. 2006; 54: 2039– 2046.
34. Nestorov I, Zitnik R, DeVries T. Pharmacokinetics of subcutaneously administered etanercept in subjects with psoriasis, Br J Clin Pharmacol 2006;62: 435–445.
35. Lovell DJ, Giannini EH, Reiff A. Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. N Engl J Med. 2000;342(11):763-9.
36. Lovell DJ, Giannini EH, Reiff A. Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. Arthritis Rheum. 2003 ;48(1):218-26.
37. Kimura Y, Pinho P, Walco G, et al. Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol. 2005;32(5):935-42.
38. Wallace CA, Ruperto N, Giannini EH. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004; 31: 2290-4.
39. Papsdorf V, Horneff G. Complete control of disease activity and remission induced by treatment with etanercept in juvenile idiopathic arthritis. Rheumatology. 2011; 50: 214-221.
40. Horneff G, Schmeling H and Biedermann T. The German etanercept registry for treatment of juvenile idiopathic arthritis, Ann Rheum Dis. 2004; 63(12): 1638–1644.
41. Giannini EH, Lovell DJ, Ilowite NT et al. Safety outcomes from a Phase IV pediatric registry: Etanercept (Enbrel) therapy in children and adolescents with juvenile rheumatoid arthritis (JRA), Arthritis and Rheum. 2004; 50(supplement):90.
42. Chaudhari, P. Romano and L.D. Mulcahy, Booley CT, Baker DG, Gathieb AB, Booley CT, Baker DG, Gathieb AB et al. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: A randomized trial, Lancet 2001; 357:1842–1846.
43. Ruperto N, Lovell D, Cuttica R, Woo P, Meiorin S, Wouters C et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum 2007; 56:3096–3106.
44. Gerloni V, Pontikaki I, Gattinara M, Fantini F: Focus on adverse events of TNF blockade in JIA in an open monocentric longterm prospective study of 163 patients. Ann Rheum Dis 2008, 67:1145- 1152.
45. Ruperto N, Lovell D, Cuttica R, Woo P, Meiorin S, Wouters C et al. Long term efficacy and safety of infliximab plus methotrexate for the treatment of polyarticular course juvenile rheumatoid arthritis: findings from an open label treatment extension. Ann Rheum Dis. 2010; 69(4): 718-22.
46. Richards JC, Tay-Kearney ML, Murray K, Manners P. Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Experiment Ophthalmol. 2005;33(5):461-8.
47. Rajaraman RT, Kimura Y, Li S. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006;113(2):308-14.
48. Guignard S, Gossec L, Salliot C, Ruyssen Witand A, Luc M, Duclas M al. Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: A retrospective study. Ann Rheum Dis. 2006;65(12):1631-4.
49. P.J. Mease, Adalimumab: An anti-TNF agent for the treatment of psoriatic arthritis, expert Opin Biol Ther. 2005; 5: 1491–1504.
50. Chang J, Girgis L. Clinical use of anti-TNF-a biological agents. A guide for GPs. Aust Fam Physician 2007; 36: 1035–8.
51. Lovell DJ, Ruperto N, Goodman S, Reiff A, Jung L, Jarasova K et all. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J. Med. 2008; 359(8). 810-820.
52. Ilowite N, Porras O, Reiff A, Rudge S, Punaro M, Martin A. et all. Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. Clin Rheumatol 2009; 28:129-137.
53. Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J: 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.
54. Lequerre T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job- Deslandre C, Fautrel B, Le Loet X, Sibilia J, Societe Francophone pour la Rhumatologie et les Maladies Inflammatoires en Pediatrie (SOFREMIP), Club Rhumatismes et Inflammation (CRI): Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset still disease: preliminary experience in France. Ann Rheum Dis 2008, 67:302-308.
55. Lovell DJ, Giannini EH, Kimura Y, Li S, Hashkes PJ, Reiff AO. Preliminary evidence for sustained bioactivity of IL-1 trap (rilonacept), A long acting IL-1 inhibitor, in systemic onset juvenile idiopathic arthritis (SJIA) [abstract]. Arthritis Rheum 2007; 56: S514.
56. Yokota S, Miyamae T, Imagawa T, Kata N, Katakua S, Mori M et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2005; 52(3):818–825.
57. Kutukculer N, Caglayan S, Aydogdu F: Study of pro-inflammatory (TNF, IL-1, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: correlations with clinical and laboratory parameters.Clin Rheumatol 1998; 17:288-292.
58. Yilmaz M, Kendirli SG, Altintas D, Bingol G, Antmen B: Cytokine levels in serum of patients with juvenile rheumatoid arthritis. Clin Rheumatol 2001; 20:30-35.
59. Yokota S, Imagawa T, Mori M, Miyame T, Aihara Y, Takei S et al. Efficacy and safety of tocilizumab in patients with systemic-onset idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 2008; 71(9617):998–1006.
60. Ruperto N, Lovell DJ, Quartier P, Paz E, Perez NR, Silva CA et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double blind, placebo controlled withdrawal trial. Lancet. 2008;372:383-391.