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Pediatric Rheumatology

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Open Access 01-12-2021 | Uveitis | Research article

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

Authors: Mireia Castillo-Vilella, Nuria Giménez, Jose Luis Tandaipan, Salvador Quintana, Consuelo Modesto

Published in: Pediatric Rheumatology | Issue 1/2021

Abstract

Background

Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce.

Methods

We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone.

Results

A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206).

According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%).

Conclusions

More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–78. https://doi.org/10.1016/S0140-6736(07)60363-8.CrossRefPubMed

Martini A, Ravelli A, Avcin T, Beresford MW, Burgos-Vargas R, Cuttica R, 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. https://doi.org/10.3899/jrheum.180168.CrossRefPubMed

Dave M, Rankin J, Pearce M, Foster HE. Global prevalence estimates of three chronic musculoskeletal conditions: Club foot, juvenile idiopathic arthritis and juvenile systemic lupus erythematosus. Pediatr Rheumatol Online J. 2020;18:1–7.CrossRef

Shoop-Worrall SJ, Oude Voshaar MA, McDonagh JE, van de Laar MA, Wulffraat N, Thomson W, et al. A common functional ability score for young people with juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2020;73(7):947–54. https://doi.org/10.1002/acr.24204.CrossRef

Rebane K, Ristolainen L, Relas H, Orenius T, Kautiainen H, Luosujärvi R, et al. Disability and health-related quality of life are associated with restricted social participation in young adults with juvenile idiopathic arthritis. Scand J Rheumatol. 2019;48(2):105–13. https://doi.org/10.1080/03009742.2018.1493140.CrossRefPubMed

Tynjälä P, Vähäsalo P, Tarkiainen M, Kröger L, Aalto K, Malin M, et al. Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial. Ann Rheum Dis. 2011;70(9):1605–12. https://doi.org/10.1136/ard.2010.143347.CrossRefPubMed

Wallace CA, Giannini EH, Spalding SJ, Hashkes PJ, O’Neil KM, Zeft AS, et al. Trial of early aggressive therapy in polyarticular juvenile idiopathic arthritis. Arthritis Rheum. 2012;64(6):2012–21. https://doi.org/10.1002/art.34343.CrossRefPubMed

Minden K, Horneff G, Niewerth M, Seipelt E, Aringer M, Aries P, et al. Time of disease-modifying antirheumatic drug start in juvenile idiopathic arthritis and the likelihood of a drug-free remission in young adulthood. Arthritis Care Res. 2019;71(4):471–81. https://doi.org/10.1002/acr.23709.CrossRef

Klein-wieringa IR, Brinkman DMC, Hissink PCE. Update on the treatment of nonsystemic juvenile idiopathic arthritis including treatment-to-target: is (drug-free) inactive disease already possible? Curr Opin Rheumatol. 2020;32(5):403–13. https://doi.org/10.1097/BOR.0000000000000727.CrossRefPubMed

10.

Giancane G, Ruperto N. Treatment of juvenile idiopathic arthritis: what’ s new? Curr Opin Rheumatol. 2019;31(5):428–35. https://doi.org/10.1097/BOR.0000000000000632.CrossRefPubMed

11.

Consolaro A, Giancane G, Schiappapietra B, Davì S, Calandra S, Lanni S, et al. Clinical outcome measures in juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2016;14:1–8.CrossRef

12.

Minden K, Kiessling U, Listing J, Niewerth M, Döring E, Meincke J, et al. Prognosis of patients with juvenile chronic arthritis and juvenile spondyloarthropathy. J Rheumatol. 2000;27(9):2256–63.PubMed

13.

Halyabar O, Mehta J, Ringold S, Rumsey DG, Horton DB. Treatment withdrawal following remission in juvenile idiopathic arthritis: a systematic review of the literature. Paediatr Drugs. 2019;21(6):469–92. https://doi.org/10.1007/s40272-019-00362-6.CrossRefPubMedPubMedCentral

14.

Azevedo SA, Ramos Rodrigues J, Guimarães F, Almeida D, Pinto AS, Parente H, et al. Strategies for the withdrawal of classic and biological DMARD in clinically inactive patients with juvenile idiopathic arthritis. Acta Reumatol Port. 2020;45(3):229–32.PubMed

15.

Horton DB, Onel KB, Beukelman T, Ringold S. Attitudes and approaches for withdrawing drugs for children with clinically inactive nonsystemic JIA: a survey of the childhood arthritis and rheumatology research alliance. J Rheumatol. 2017;44(3):352–60. https://doi.org/10.3899/jrheum.161078.CrossRefPubMedPubMedCentral

16.

Prince FH, Twilt M, Simon SC, van Rossum MA, Armbrust W, Hoppenreijs EP, et al. When and how to stop etanercept after successful treatment of patients with juvenile idiopathic arthritis. Ann Rheum Dis. 2009;68(7):1228–9. https://doi.org/10.1136/ard.2008.101030.CrossRefPubMed

17.

Shoop-Worrall SJW, Kearsley-Fleet L, Thomson W, Verstappen SMM, Hyrich KL. How common is remission in juvenile idiopathic arthritis: a systematic review. Semin Arthritis Rheum. 2017;47(3):331–7. https://doi.org/10.1016/j.semarthrit.2017.05.007.CrossRefPubMedPubMedCentral

18.

Shoop-Worrall SJW, Verstappen SMM, McDonagh JE, Baildam E, Chieng A, Davidson J, et al. Long-term outcomes following achievement of clinically inactive disease in juvenile idiopathic arthritis: the importance of definition. Arthritis Rheumatol. 2018;70(9):1519–29. https://doi.org/10.1002/art.40519.CrossRefPubMedPubMedCentral

19.

Cai Y, Liu X, Zhang W, Xu J, Cao L. Clinical trial of etanercept tapering in juvenile idiopathic arthritis during remission. Rheumatol Int. 2013;33(9):2277–82. https://doi.org/10.1007/s00296-012-2642-7.CrossRefPubMed

20.

Chang CY, Meyer RML, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015;67(5):658–66. https://doi.org/10.1002/acr.22477.CrossRef

21.

Modesto C, Antón J, Rodriguez B, Bou R, Arnal C, Ros J, et al. Incidence and prevalence of juvenile idiopathic arthritis in Catalonia (Spain). Scand J Rheumatol. 2010;39(6):472–9. https://doi.org/10.3109/03009741003742722.CrossRefPubMed

22.

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31:390–2.PubMed

23.

Wallace CA, Ruperto N, Giannini E. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004;31(11):2290–4.PubMed

24.

Wallace CA, Giannini EH, Huang BIN, Itert L. American College of Rheumatology Provisional Criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res. 2011;63(7):929–36. https://doi.org/10.1002/acr.20497.CrossRef

25.

Glerup M, Herlin T, Twilt M. Clinical outcome and long-term remission in JIA. Curr Rheumatol Rep. 2017;19(12):75. https://doi.org/10.1007/s11926-017-0702-4.CrossRefPubMed

26.

Shenoi S, Wallace CA. Remission in juvenile idiopathic arthritis: current facts. Curr Rheumatol Rep. 2010;12(2):80–6. https://doi.org/10.1007/s11926-010-0085-2.CrossRefPubMed

27.

Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the reacch-out cohort. Ann Rheum Dis. 2015;74(10):1854–60. https://doi.org/10.1136/annrheumdis-2014-205372.CrossRefPubMed

28.

Raab A, Sengler C, Niewerth M, Klotsche J, Horneff G, Zink A, et al. Comorbidity profiles among adult patients with juvenile idiopathic arthritis: results of a biologic register. Clin Exp Rheumatol. 2013;31(5):796–802.PubMed

29.

Simon TA, Harikrishnan GP, Kawabata H, Singhal S, Brunner HI, Lovell DJ. Prevalence of co-existing autoimmune disease in juvenile idiopathic arthritis: a cross-sectional study. Pediatr Rheumatol Online J. 2020;18(1):43. https://doi.org/10.1186/s12969-020-00426-9.CrossRefPubMedPubMedCentral

30.

Hügle B, Horneff G. The role of synthetic drugs in the biologic era: therapeutic strategies for treating juvenile idiopathic arthritis. Expert Opin Pharmacother. 2016;17(5):703–14. https://doi.org/10.1517/14656566.2016.1133592.CrossRefPubMed

31.

Barut K, Adrovic A, Şahin S, Kasapçopur Ö. Juvenile idiopathic arthritis. Balkan Med J. 2017;34(2):90–101. https://doi.org/10.4274/balkanmedj.2017.0111.CrossRefPubMedPubMedCentral

32.

Selvaag AM, Flatø B, Dale K, Lien G, Vinje O, Smerdel-Ramoya A, et al. Radiographic and clinical outcome in early juvenile rheumatoid arthritis and juvenile spondyloarthropathy: a 3-year prospective study. J Rheumatol. 2006;33(7):1382–91.PubMed

33.

Vilca I, Munitis PG, Pistorio A, Ravelli A, Buoncompagni A, Bica B, et al. Predictors of poor response to methotrexate in polyarticular-course juvenile idiopathic arthritis: analysis of the PRINTO methotrexate trial. Ann Rheum Dis. 2010;69(8):1479–83. https://doi.org/10.1136/ard.2009.120840.CrossRefPubMed

34.

van Dijkhuizen EH, Wulffraat NM. Prediction of methotrexate efficacy and adverse events in patients with juvenile idiopathic arthritis: a systematic literature review. Pediatr Rheumatol Online J. 2014;12(1):51. https://doi.org/10.1186/1546-0096-12-51.CrossRefPubMedPubMedCentral

35.

Ravelli A, Felici E, Magni-Manzoni S, Pistorio A, Novarini C, Bozzola E, et al. Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis Rheum. 2005;52(3):826–32. https://doi.org/10.1002/art.20945.CrossRefPubMed

36.

Ma X, Xin L, Sun J, Liu Z. Antinuclear antibody-positive cohort constitutes homogeneous entity in juvenile idiopathic arthritis. Mod Rheumatol. 2016;26(1):75–9. https://doi.org/10.3109/14397595.2015.1056993.CrossRefPubMed

37.

Glerup M, Herlin T, Twilt M. Remission rate is not dependent on the presence of antinuclear antibodies in juvenile idiopathic arthritis. Clin Rheumatol. 2017;36(3):671–6. https://doi.org/10.1007/s10067-017-3540-x.CrossRefPubMed

38.

Albers HM, Brinkman DM, Kamphuis SS, van Suijlekom-Smit LW, van Rossum MA, Hoppenreijs EP, et al. Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2010;62(2):204–12. https://doi.org/10.1002/acr.20069.CrossRef

39.

Flatø B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V, et al. Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years. J Rheumatol. 2003;30(2):386–93.PubMed

40.

van Rossum MA, Zwinderman AH, Boers M, Dijkmans BA, van Soesbergen RM, Fiselier TJW, et al. Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method. Arthritis Rheum. 2003;48(2):507–15. https://doi.org/10.1002/art.10783.CrossRefPubMed

41.

Berntson L, Damgård M, Andersson-Gäre B, Herlin T, Nielsen S, Nordal E, et al. HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis. J Rheumatol. 2008;35(10):2055–61.PubMed

42.

Berntson L, Nordal E, Aalto K, Peltoniemi S, Herlin T, Zak M, et al. HLA-B27 predicts a more chronic disease course in an 8-year follow-up cohort of patients with juvenile idiopathic arthritis. J Rheumatol. 2013;40(5):725–31. https://doi.org/10.3899/jrheum.121257.CrossRefPubMed

43.

Klotsche J, Minden K, Niewerth M, Horneff G. Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA. Ann Rheum Dis. 2018;77(7):996–1002. https://doi.org/10.1136/annrheumdis-2017-211968.CrossRefPubMed

44.

Nordal E, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Ongoing disease activity and changing categories in a long-term nordic cohort study of juvenile idiopathic arthritis. Arthritis Rheum. 2011;63(9):2809–18. https://doi.org/10.1002/art.30426.CrossRefPubMed

Title: Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach
Authors: Mireia Castillo-Vilella
Nuria Giménez
Jose Luis Tandaipan
Salvador Quintana
Consuelo Modesto
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Uveitis
Juvenile Rheumatoid Arthritis
Methotrexate
Methotrexate
Juvenile Rheumatoid Arthritis
Published in: Pediatric Rheumatology / Issue 1/2021
Electronic ISSN: 1546-0096
DOI: https://doi.org/10.1186/s12969-021-00607-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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