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When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

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Abstract

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07–1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD.

Conclusion: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs.

What is Known:

• Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections.

• Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies.

What is New:

• Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up.

• The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

ANA:

Anti-nuclear antibody

bDMARD:

Biological disease modifying anti-rheumatic drug

cDMARD:

Conventional disease modifying antirheumatic drugs

IACI:

Intraarticular corticosteroid injection

ILAR:

International League of Associations for Rheumatology

JIA:

Juvenile idiopathic arthritis

MTX:

Methotrexate

NSAID:

Non-steroidal anti-inflammatory drug

References

  1. Zaripova LN, Midgley A, Christmas SE, Beresford MW, Baildam EM, Oldershaw RA (2021) Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol 19(1):135. https://doi.org/10.1186/s12969-021-00629-8

    Article  Google Scholar 

  2. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton 2001. J Rheumatol 31(2):390–392

    PubMed  Google Scholar 

  3. Okamoto N, Yokota S, Takei S, OkuraY KT, Shimizu M et al (2018) Clinical practice guidance for juvenile idiopathic arthritis (JIA) 2018. Mod Rheumatol 29(1):41–59. https://doi.org/10.1080/14397595.2018.1514724

    Article  PubMed  Google Scholar 

  4. Beukelman T, Patkar NM, Saag KG, Tolleson-Rinehart S, Cron RQ, DeWitt EM et al (2011) 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken) 63:465–482. https://doi.org/10.1002/acr.20460

    Article  PubMed  Google Scholar 

  5. Vanoni F, Minoia F, Malattia C (2017) Biologics in juvenile idiopathic arthritis: a narrative review. Eur J Pediatr 176(9):1147–1153. https://doi.org/10.1007/s00431-017-2960-6

    Article  CAS  PubMed  Google Scholar 

  6. Ruperto N, Lovell DJ, Cuttica R, Woo P, Meiorin S, Wouters C et al (2010) 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 69(4):718–722. https://doi.org/10.1136/ard.2009.100354

    Article  CAS  PubMed  Google Scholar 

  7. Onel KB, Horton DB, Lovell DJ, Shenoi S, Cuello CA, Angelas-Han ST et al (2022) 2021 American College of Rheumatology guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for oligoarthritis, temporomandibular joint arthritis, and systemic juvenile idiopathic arthritis. Arthritis Rheumatol 74(4):553–569. https://doi.org/10.1002/art.42037

    Article  PubMed  PubMed Central  Google Scholar 

  8. Consolaro A, Giancane G, Schiappapietra B, Davi S, Calandra S, Lanni S et al (2016) Clinical outcome measures in juvenile idiopathic arthritis. Pediatr Rheumatol Online J 14(1):23. https://doi.org/10.1186/s12969-016-0085-5

    Article  PubMed  PubMed Central  Google Scholar 

  9. Demirkaya E, Ozen S, Bilginer Y, Aktay Ayaz N, Bora Makay B, Ünsal E et al (2011) The distribution of juvenile idiopathic arthritis in the eastern Mediterranean: results from the registry of the Turkish Paediatric Rheumatology Association. Clin Exp Rheumatol 29(1):111–116

    PubMed  Google Scholar 

  10. Shen CC, Yeh KW, Ou LS, Yao TC, Chen LC, Huang JL (2013) Clinical features of children with juvenile idiopathic arthritis using the ILAR classification criteria: a community-based cohort study in Taiwan. J Microbiol Immunol Infect 46(4):288–294. https://doi.org/10.1016/j.jmii.2012.03.006

    Article  PubMed  Google Scholar 

  11. Horneff G, De Bock F, Foeldvari I, Girschick HJ, Michels H, Moebius D et al (2009) Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis 68(4):519–525. https://doi.org/10.1136/ard.2007.087593

    Article  CAS  PubMed  Google Scholar 

  12. Klein-Wieringa IR, Brinkman DMC, Cate R, Hissink Muller PCE (2020) Uptodate on the treatment of nonsystemic juvenile idiopathic arthritis including treatment to target: is (drug-free) inactive disease already possible? Curr Opin Rheumatol 32(5):403–413. https://doi.org/10.1097/BOR.0000000000000727

    Article  CAS  PubMed  Google Scholar 

  13. Özdel S, Bağlan E, Kargın Çakıcı E, Yazılıtaş F, Yücel H, Senel S et al (2021) Clinical features in 305 patients with juvenile idiopathic arthritis: a single center Turkish study. Pediatr Int 63(6):636–642. https://doi.org/10.1111/ped.14481

    Article  PubMed  Google Scholar 

  14. Otten MH, Anink J, Prince FH, Twilt M, Vastert SJ, Ten Cate R et al (2015) Trends in prescription of biological agents and outcomes of juvenile idiopathic arthritis: results of the Dutch national arthritis and biologics in children register. Ann Rheum Dis 74(7):1379–1386. https://doi.org/10.1136/annrheumdis-2013-204641

    Article  PubMed  Google Scholar 

  15. Davies R, Carrasco R, Foster HE, Baildam EM, Chieng SEA, Davidson JE et al (2016) Treatment prescribing patterns in patients with juvenile idiopathic arthritis (JIA): analysis from the UK Childhood Arthritis Prospective Study (CAPS). Semin Arthritis Rheum 46(2):190–195. https://doi.org/10.1016/j.semarthrit.2016.06.001

    Article  PubMed  PubMed Central  Google Scholar 

  16. Batu ED, Sönmez HE, Gülhan BG, Arıcı ZS, Topaloğlu R, Bilginer Y (2017) Predictors of methotrexate response in Turkish children with oligoarticular and polyarticular juvenile idiopathic arthritis. Turk J Pediatr 59(1):6–12. https://doi.org/10.24953/turkjped.2017.01.002

    Article  PubMed  Google Scholar 

  17. Petty RE, Laxer RM, Lindsley CB, Wedderburn LR, Mellins ED, Fuhlbrigge RC (2021) Oligoarticular juvenile idiopathic arthritis. Textbook of Pediatric Rheumatology, 8th edn. Philedephia, pp 241–250

    Google Scholar 

  18. Al-Matar MJ, Petty RE, Tucker LB, Malleson PN, Schroeder ML, Cabral DA (2002) The early pattern of joint involvement predicts disease progression in children with oligoarticular (pauciarticular) juvenile rheumatoid arthritis. Arthritis Rheumatol 46(10):2708–2715. https://doi.org/10.1002/art.10544

    Article  Google Scholar 

  19. Padeh S, Pinhas-Hamiel O, Zimmermann-Sloutskis D, Berkun Y (2011) Children with oligoarticular juvenile idiopathic arthritis are at considerable risk for growth retardation. J Pediatr 159(5):832–837. https://doi.org/10.1016/j.jpeds.2011.04.012

    Article  PubMed  Google Scholar 

  20. Pelegrin L, Casaroli-Marano R, Anton J, Vicuna MCG, Molina-Prat N, Aro´stegui JI, et al (2014) Predictive value of selected biomarkers, polymorphisms, and clinical features for oligoarticular juvenile idiopathic arthritis-associated uveitis. Ocul Immunol Inflamm 22(3):208–212. https://doi.org/10.3109/09273948.2013.841495

    Article  CAS  PubMed  Google Scholar 

  21. Guıllaume S, Prıeur AM, Coste J, Job-Deslandre C (2000) Long-Term Outcome and Prognosıs in Olıgoartıcular-onset Juvenıle Idıopathıc Arthrıtıs. Arthrıtıs Rheumatısm 43:1858–1865

    Article  PubMed  Google Scholar 

  22. Swart JF, van Dijkhuizen EHP, Wulffraat NM, Roock S (2018) Clinical Juvenile Arthritis Disease Activity Score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis. Ann Rheum Dis 77(3):336–342. https://doi.org/10.1136/annrheumdis-2017-212104

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Rheumatology, Department of Pediatrics, University of Health Sciences, Ankara City Hospital, 06800-Bilkent, Ankara, Turkey

    Merve Cansu Polat, Elif Çelikel, Zahide Ekici Tekin, Tuba Kurt, Melike Mehveş Kaplan, Vildan Güngörer, Nilüfer Tekgöz, Müge Sezer, Cüneyt Karagöl, Serkan Coşkun, Nimet Öner & Banu Çelikel Acar

  2. Division of Rheumatology, Department of Internal Medicine, Ankara Training and Research Hospital, 06230-Altındağ, Ankara, Turkey

    Serdar Sezer

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  1. Merve Cansu Polat
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Contributions

Conceptualization: MCP, SC, BÇA. Methodology: VG, EÇ, ZET, CK. Formal analysis and investigation: SS, MS, NT, NÖ, TK, MMK. Writing - original draft preparation: MCP. Writing - review and editing: MCP, BÇA. Supervision: BÇA.

Corresponding author

Correspondence to Merve Cansu Polat.

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Ethics approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. The study described has been carried out in accordance with abovementioned standards and has been approved by the Ethics Committee of Ankara City Hospital (E2-22–2740).

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The authors declare no competing interests.

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Communicated by Peter de Winter

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Polat, M.C., Çelikel, E., Tekin, Z.E. et al. When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05538-y

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