Novelties in juvenile idiopathic arthritis – what pediatricians need to know

Authors

  • Marijan Frković Klinički bolnički centar Zagreb, Kišpatićeva 12, 10000 Zagreb
  • Marija Jelušić Klinički bolnički centar Zagreb, Kišpatićeva 12, 10000 Zagreb

DOI:

https://doi.org/10.13112/pc.1073

Keywords:

ARTHRITIS, JUVENILE; CLASSIFICATION; BIOLOGICAL PRODUCTS; JANUS KINASE INHIBITORS

Abstract

Objective: The paper offers a comprehensive overview of recent advances in the understanding of the causes, classification, and treatment of juvenile idiopathic arthritis (JIA).

Methods: A systematic review of the most recent literature was conducted.

Results: Juvenile idiopathic arthritis is among the most prevalent chronic illnesses in children. Advances in the understanding of the disease's causes and progression triggered the creation and use of novel treatments - biologic medications and Janus kinase (JAK) inhibitors - leading to significantly enhanced treatment outcomes for a substantial but not the entire number of patients. The disease classification, which currently divides JIA into 7 types based on initial clinical characteristics, no longer aligns with contemporary scientific understanding and restricts the registration of new medications. A revised classification system is being developed, which will primarily consider the genetic and immunological features of the patient when categorizing the disease. This is expected to result in the quicker deployment of future therapeutic treatments.

Conclusion: Advances in understanding the causes and development of JIA have driven the creation of novel medications and enhanced treatment results. Furthermore, they promoted the creation of a novel disease classification system, whose main aim is to facilitate the production and approval of next-generation medications, which in turn is a step towards achieving the ultimate objective of permanent stable remission for all patients with JIA.

References

1. Chen K, Zeng H, Togizbayev G, Martini A, Zeng H. New classification criteria for juvenile idiopathic arthritis. Int J Rheum Dis. 2023;26:1889-92.

2. Martini A, Lovell DJ, Albani S, et al. Juvenile idiopathic arthritis. Nat Rev Dis Primers. 2022;8(1):5.

3. Zaripova LN, Midgley A, Christmas SE, Beresford MW, Baildam EM, Oldershaw RA. Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol Online J. 2021;19(1):135.

4. McCurdy D, Parsa MF. Updates in juvenile idiopathic arthritis. Adv Pediatr. 2021;68:143-70.

5. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390-2.

6. Eng SW, Duong TT, Rosenberg AM, et al. The biologic basis of clinical heterogeneity in juvenile idiopathic arthritis. Arthritis Rheumatol. 2014;66:34-63.

7. Chhabra A, Robinson C, Houghton K, et al. Long-term outcomes and disease course of children with juvenile idiopathic arthritis in the ReACCh-out cohort: a two-centre experience. Rheumatology (Oxford). 2020;59(12):3727-30.

8. Martini A, Ravelli A, Avcin T, et al. Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization international consensus. J Rheumatol. 2019;46(2):190-7.

9. Martini A. Are there new targets for juvenile idiopathic arthritis? Semin Arthritis Rheum. 2019;49(3S):S11-S13.

10. Nigrovic PA, Colbert RA, Holers VM, et al. Biological classification of childhood arthritis: roadmap to a molecular nomenclature. Nat Rev Rheumatol. 2021;17(5):257-69.

11. Martini A. It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 2012;71(9):1437-9.

12. Ravelli A, Varnier GC, Oliveira S, et al. Antinuclear antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63:267-75.

13. Martini A, Ravelli A, Avcin T, et al. Pediatric Rheumatology International Trials Organization (PRINTO). Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization international consensus. J Rheumatol. 2019;46:190-7.

14. Jelušić M. Juvenilni idiopatski artritis. In: Jelušić M, Malčić I, editors. Pedijatrijska reumatologija. 1st ed. Zagreb: Medicinska naklada; 2014. p. 160-81.

15. Thierry S, Fautrel B, Lemelle I, et al. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Joint Bone Spine. 2014;81:112-7.

16. De Silvestri A, Capittini C, Poddighe D, et al. HLA-DRB1 alleles and juvenile idiopathic arthritis: diagnostic clues emerging from a meta-analysis. Autoimmun Rev. 2017;16(12):1230-6.

17. Ombrello MJ, Remmers EF, Tachmazidou I, et al. HLA-DRB111 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis. Proc Natl Acad Sci U S A. 2015;112:15970-5.

18. Mistry RR, Patro P, Agarwal V, Misra DP. Enthesitis-related arthritis: current perspectives. Open Access Rheumatol Res Rev. 2019;11:19-31.

19. Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011;7(7):416-26.

20. Ombrello MJ, Arthur VL, Remmers EF, et al. Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: clinical and therapeutic implications. Ann Rheum Dis. 2017;76:906-13.

21. Rigante D, Bosco A, Esposito S. The etiology of juvenile idiopathic arthritis. Clin Rev Allergy Immunol. 2015;49(2):253-61.

22. Horton DB, Shenoi S. Review of environmental factors and juvenile idiopathic arthritis. Open Access Rheumatol. 2019;11:253-67.

23. Nistala K, Moncrieffe H, Newton KR, Varsani H, Hunter P, Wedderburn LR. Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum. 2008;58(3):875-87.

24. Stoll ML, Punaro M. Psoriatic juvenile idiopathic arthritis: a tale of two subgroups. Curr Opin Rheumatol. 2011;23(5):437-43.

25. Correll CK, Binstadt BA. Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. Pediatr Res. 2014;75(1-2):176-83.

26. Minoia F, Davi S, Horne A, et al. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014;66(11):3160-9.

27. de Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis. 2007;66(5):589-98.

28. Berntson L, Nordal E, Fasth A, et al. Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA). Pediatr Rheumatol Online J. 2014;12(1):22.

29. Mahmud SA, Binstadt BA. Autoantibodies in the pathogenesis, diagnosis, and prognosis of juvenile idiopathic arthritis. Front Immunol. 2019;9:3168.

30. Petty RE, Lindsley CB. Oligoarticular juvenile idiopathic arthritis. In: Petty RE, Laxer RM, Lindsley CB, et al., editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

31. Rosenberg AM, Kiem GO. Polyarticular juvenile idiopathic arthritis. In: Petty RE, Laxer RM, Lindsley CB, et al., editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

32. Tse SML, Petty RE. Enthesitis-related arthritis. In: Petty RE, Laxer RM, Lindsley CB, et al., editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

33. Nigrovic PA, Sundel RP. Psoriatic arthritis. In: Petty RE, Laxer RM, Lindsley CB, et al., editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

34. DeBenedetti F, Schneider R. Systemic juvenile idiopathic arthritis. In: Petty RE, Laxer RM, Lindsley CB, Wedderburn LR, editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

35. Davies R, Southwood T, Kearsley-Fleet L, et al. Mortality rates are increased in patients with systemic juvenile idiopathic arthritis. Arch Dis Child. 2017;102:206-7.

36. Lindsley CB, Laxer RM. Arthropathies of inflammatory bowel disease. In: Petty RE, Laxer RM, Lindsley CB, et al., editors. Textbook of Pediatric Rheumatology. Philadelphia: Elsevier; 2016.

37. Stoll ML, Kau CH, Waite PD, et al. Temporomandibular joint arthritis in juvenile idiopathic arthritis, now what? Pediatr Rheumatol Online J. 2018;16:32.

38. Angeles-Han ST, Ringold S, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation guideline for the screening, monitoring, and treatment of juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res (Hoboken). 2019;71:703-16.

39. Ravelli A, Minoia F, Davì S, et al. 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. Ann Rheum Dis. 2016;75:481-9.

40. Janow GL, Panghaal V, Trinh A, et al. Detection of active disease in juvenile idiopathic arthritis: sensitivity and specificity of the physical examination vs ultrasound. J Rheumatol. 2011;38:2671-4.

41. Weiss PF, Arabshahi B, Johnson A, et al. High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound. Arthritis Rheum. 2008;58(4):1189-96.

42. Ravelli A, Consolaro A, Horneff G, et al. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2018;77(6):819-28.

43. Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non-Systemic Polyarthritis, Sacroiliitis, and Enthesitis. Arthritis Care Res (Hoboken). 2019;71(6):717-34.

44. Gillard L, Pouchot J, Cohen-Aubart F, et al. JAK inhibitors in difficult-to-treat adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis. Rheumatology (Oxford). 2022;62(4):1594-604.

45. Rahman MM, Laila K, Rahman SA. Efficacy and safety of tofacitinib in the treatment of refractory cases of polyarticular course juvenile idiopathic arthritis: a study from Bangladesh. Int J Rheum Dis. 2022;25(6):678-84.

46. Arvonen M, Vänni P, Sarangi AN, et al. Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray? Immunol Rev. 2020;294(1):9-26.

47. Little EM, Grevich S, Huber JL, et al. Parental perception of dietary intervention in juvenile idiopathic arthritis. J Altern Complement Med. 2019;25(6):643-7.

48. Vaghef-Mehrabany E, Alipour B, Homayouni-Rad A, et al. Probiotic supplementation improves inflammatory status in patients with rheumatoid arthritis. Nutrition. 2014;30(4):430-5.

49. Finch SL, Rosenberg AM, Vatanparast H. Vitamin D and juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2018;16(1):34.

50. Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol. 2017;13(8):466-79.

Published

2025-04-02

How to Cite

Frković, M., & Jelušić, M. (2025). Novelties in juvenile idiopathic arthritis – what pediatricians need to know. Paediatria Croatica, 69(Suppl 2), 191-202. https://doi.org/10.13112/pc.1073

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