Skip to main content

Advertisement

SpringerLink
Log in

Criteria to define response to therapy in paediatric rheumatic diseases

  • Special Article
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

In this review we describe the general methodology and the results of the international projects, conducted by the Paediatric Rheumatology International Trials Organisation (PRINTO), in collaboration with the Paediatric Rheumatology Collaborative Study Group (PRCSG). The aim of these projects were to identify and validate criteria for the evaluation of response to therapy in clinical trials and in daily clinical practice in patients with the three major paediatric rheumatic diseases (PRD): juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE).

Methods

The methodological approach to identify and validate outcome measures can be divided into three main phases: (1) the development of a preliminary core set of measures to evaluate the outcome (e.g. response to therapy, remission criteria, disease activity or damage etc.) through literature review and consensus techniques; (2) a large-scale data collection for a prospectively evidence-based validation of the preliminary findings; (3) the final development of a validated criteria for the evaluation of the outcome.

Results

The core sets for three diseases included domains that are common to all diseases (physician’s global assessment of disease activity; parent’s global assessment of the overall patient’s well-being; disability and/or health-related quality of life) plus additional domains that are specific for each disease. In order to be classified as a responder to a given treatment, a patient should demonstrate a different minimum level of improvement (≥30% in JIA, ≥20% in JDM, and ≥50% in JSLE) with no more than one of the remaining variables worsening by more than 30%.

Conclusions

The proposed core sets and definitions of improvement incorporate clinically meaningful change in a composite endpoint for the evaluation of global response to therapy in the major PRD. The definitions are proposed for use in PRD clinical trials and may help physicians to decide if a child has responded adequately to therapy.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Food and Drug Administration (FDA) (1998) Regulations requiring manufacturers to assess the safety and effectiveness of new drugs and biologic products in pediatrics patients (21 CFR Parts 201, 312, 314, and 601). Fed Regist 63(231)

  2. Regulation (EC) (2006) no 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Union L 378:1–19

  3. Connor JD (1999) A look at the future of pediatric therapeutics: an investigator's perspective of the new pediatric rule. Pediatrics 104(3):610–613

    PubMed  CAS  Google Scholar 

  4. Ruperto N, Martini A, for the Paediatric Rheumatology International Trials Organization (PRINTO) (2000) Use of unlabelled and off licence drugs in children. A European paediatric rule is needed to protect children. Br Med J 320(7243):1210–1211

    Article  CAS  Google Scholar 

  5. Ruperto N, Martini A (2004) International research networks in pediatric rheumatology: the PRINTO perspective. Curr Opin Rheumatol 16(5):566–570

    Article  PubMed  Google Scholar 

  6. Ruperto N, Meiorin S, Iusan SM et al (2008) Consensus procedures and their role in pediatric rheumatology. Curr Rheumatol Rep 10(2):142–146

    Article  PubMed  Google Scholar 

  7. Delbecq AL, Van de Ven AH, Gustafson DH (1975) Group techniques for program planning. A guide to nominal group and Delphi processes. Scott Foresman and Co, Glenview

  8. Sniderman AD (1999) Clinical trials, consensus conferences, and clinical practice. Lancet 354(9175):327–330

    Article  PubMed  CAS  Google Scholar 

  9. Giannini EH, Ruperto N, Ravelli A et al (1997) Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 40(7):1202–1209

    PubMed  CAS  Google Scholar 

  10. Ruperto N, Ravelli A, Falcini F et al (1998) Performance of the preliminary definition of improvement in juvenile chronic arthritis patients treated with methotrexate. Ann Rheum Dis 57(1):38–41

    Article  PubMed  CAS  Google Scholar 

  11. Felson DT, Anderson JJ, Boers M et al (1995) American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38:727–735

    Article  PubMed  CAS  Google Scholar 

  12. Strand V, Gladman D, Isenberg D et al (1999) Outcome measures to be used in clinical trials in systemic lupus erythematosus. J Rheumatol 26(2):490–497

    PubMed  CAS  Google Scholar 

  13. Smolen JS, Strand V, Cardiel M et al (1999) Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: consensus on a preliminary core set of outcome domains. J Rheumatol 26(2):504–507

    PubMed  CAS  Google Scholar 

  14. Rider LG, Giannini EH, Harris-Love M et al (2003) Defining clinical improvement in adult and juvenile myositis. J Rheumatol 30(3):603–617

    PubMed  Google Scholar 

  15. Rider LG, Giannini EH, Brunner HI et al (2004) International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum 50(7):2281–2290

    Article  PubMed  Google Scholar 

  16. Oddis CV, Rider LG, Reed AM et al (2005) International consensus guidelines for trials of therapies in the idiopathic inflammatory myopathies. Arthritis Rheum 52(9):2607–2615

    Article  PubMed  Google Scholar 

  17. Ruperto N, Ravelli A, Murray KJ et al (2003) Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis. Rheumatol Oxf 42(12):1452–1459

    Article  Google Scholar 

  18. Ruperto N, Ravelli A, Cuttica R et al (2005) The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set. Arthritis Rheum 52(9):2854–2864

    Article  PubMed  Google Scholar 

  19. Ruperto N, Ravelli A, Oliveira S et al (2006) The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus. Prospective validation of the definition of improvement. Arthritis Rheum 55(3):355–363

    Article  PubMed  Google Scholar 

  20. Ruperto N, Ravelli A, Pistorio A et al (2008) The provisional Pediatric Rheumatology International Trial Organization/American College of Rheumatology/European League Against Rheumatism disease activity core set for the evaluation of response to therapy in juvenile dermatomyositis: a prospective validation study. Arthritis Rheum 59(1):4–13

    Article  PubMed  Google Scholar 

  21. Boers M, Brooks P, Strand CV, Tugwell P (1998) The OMERACT filter for outcome measures in rheumatology. J Rheumatol 25(2):198–199

    PubMed  CAS  Google Scholar 

  22. Bellamy N (1999) Clinimetric concepts in outcome assessment: the OMERACT filter. J Rheumatol 26(4):948–950

    PubMed  CAS  Google Scholar 

  23. Liang MH, Fossel AH, Larson MG (1990) Comparisons of five health status instruments for orthopedic evaluation. Med Care 28(7):632–642

    Article  PubMed  CAS  Google Scholar 

  24. Cronbach LJ (1951) Coefficient alfa and the internal structure of tests. Psychometrika 16:297–334

    Article  Google Scholar 

  25. Filocamo G, Davì S, Pistorio A et al (2010) Comparison of 21-numbered circle and 10-centimeter horizontal line visual analog scales for physician's and parent's subjective ratings in juvenile idiopathic arthritis. J Rheumatol 37:1534–1541

    Google Scholar 

  26. Singh G, Athreya BH, Fries JF, Goldsmith DP (1994) Measurement of health status in children with juvenile rheumatoid arthritis. Arthritis Rheum 37:1761–1769

    Article  PubMed  CAS  Google Scholar 

  27. Martini A, Ruperto N, for the Paediatric Rheumatology International Trials Organization (PRINTO) (Guest eds) (2001) Quality of life in juvenile idiopathic arthritis patients compared to healthy children. Clin Exp Rheumatol 19[Suppl. 23]:S1–S172

  28. Ruperto N, Ravelli A, Pistorio A et al (2001) Cross-cultural adaptation and psychometric evaluation of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ) in 32 countries. Review of the general methodology. Clin Exp Rheumatol 19(4):S1–S9

    PubMed  CAS  Google Scholar 

  29. Filocamo G, Sztajnbok F, Cespedes-Cruz A et al (2007) Development and validation of a new short and simple measure of physical function for juvenile idiopathic arthritis. Arthritis Rheum 57(6):913–920

    Article  PubMed  Google Scholar 

  30. Landgraf JM, Abetz L, Ware JE (1996) The CHQ user's manual, 1st edn. The Health Institute, New England Medical Center, Boston

  31. Filocamo G, Schiappapietra B, Bertamino M et al (2010) A new short and simple health-related quality of life measure for paediatric rheumatic diseases: initial validation in juvenile idiopathic arthritis. Rheumatology 49:1272–1280

    Google Scholar 

  32. Cassidy JT, Levinson JE, Bass JC et al (1986) A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum 29:274–281

    Article  PubMed  CAS  Google Scholar 

  33. Ruperto N, Giannini EH (1996) Redundancy of conventional articular response variables used in juvenile chronic arthritis clinical trials. Ann Rheum Dis 55:73–75

    Article  PubMed  CAS  Google Scholar 

  34. Ravelli A, Viola S, Ruperto N et al (1997) Correlation between conventional disease activity measures in juvenile chronic arthritis. Ann Rheum Dis 56(3):197–200

    Article  PubMed  CAS  Google Scholar 

  35. Bazso A, Consolaro A, Ruperto N et al (2009) Development and testing of reduced joint counts in juvenile idiopathic arthritis. J Rheumatol 36(1):183–190

    PubMed  Google Scholar 

  36. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35(6):630–640

    Article  PubMed  CAS  Google Scholar 

  37. Liang MH, Socher SA, Larson MG, Schur PH (1989) Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 32:1107–1118

    Article  PubMed  CAS  Google Scholar 

  38. Vitali C, Bencivelli W, Isenberg DA et al (1992) Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. Clin Exp Rheumatol 10:541–547

    PubMed  CAS  Google Scholar 

  39. Vitali C, Bencivelli W, Mosca M et al (1999) Development of a clinical chart to compute different disease activity indices for systemic lupus erythematosus. J Rheumatol 26(2):498–501

    PubMed  CAS  Google Scholar 

  40. Lovell DJ, Lindsley CB, Rennebohm RM et al (1999) Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies—II. The Childhood Myositis Assessment Scale (CMAS): a quantitative tool for the evaluation of muscle function. Arthritis Rheum 42(10):2213–2219

    Article  PubMed  CAS  Google Scholar 

  41. Rennebohm RM, Jones K, Huber AM et al (2004) Normal scores for nine maneuvers of the childhood myositis assessment scale. Arthritis Rheum Arthritis Care Res 51(3):365–370

    Article  Google Scholar 

  42. Huber AM, Feldman BM, Rennebohm RM et al (2004) Validation and clinical significance of the childhood myositis assessment scale for assessment of muscle function in the juvenile idiopathic inflammatory myopathies. Arthritis Rheum 50(5):1595–1603

    Article  PubMed  Google Scholar 

  43. Hicks J, Wesley R, Koziol D et al (2000) Validation of manual muscle testing (MMT) in the assessment of juvenile dermatomyositis (JDM). Arthritis Rheum 43[Suppl]:S194

    Google Scholar 

  44. Bode RK, Klein-Gitelman MS, Miller ML, Lechman TS, Pachman LM (2003) Disease activity score for children with juvenile dermatomyositis: reliability and validity evidence. Arthritis Rheum Arthritis Care Res 49(1):7–15

    Article  Google Scholar 

  45. Isenberg DA, Allen E, Farewell V et al (2004) International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology 43(1):49–54

    Article  PubMed  CAS  Google Scholar 

  46. Giannini EH, Lovell DJ, Silverman ED et al (1996) Intravenous immunoglobulin in the treatment of polyarticular juvenile rheumatoid arthritis: a phase I/II study. J Rheumatol 23(5):919–924

    PubMed  CAS  Google Scholar 

  47. Brunner HI, Lovell DJ, Finck BK, Giannini EH (2002) Preliminary definition of disease flare in juvenile rheumatoid arthritis. J Rheumatol 29(5):1058–1064

    PubMed  Google Scholar 

  48. Wallace CA, Ruperto N, Giannini E et al (2004) Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 31(11):2290–2294

    PubMed  Google Scholar 

Download references

Acknowledgements

This contribution is part of the Task-force in Europe for Drug Development for the Young (TEDDY) Network of Excellence supported by the European Commission’s Sixth Framework Program (Contract n. 0005216 LSHBCT- 2005-005126).

We are indebted to PRINTO national coordinators and to the members of the PRINTO and PRCSG networks, whose enthusiastic participation made these projects possible. The project has been supported by grant from the European Union (contract no. BMH4983531-CA, no. QLG1-CT-2000-00514), by IRCCS G. Gaslini, Genoa, Italy, and by the National Institute of Health (Grant RO3 AI 44046). Dr Dinara Guseinova, is a recipient of a EULAR scholarship.

Author information

Authors and Affiliations

  1. IRCCS G. Gaslini, Pediatria II, Reumatologia, Pædiatric Rheumatology International Trials Organisation (PRINTO), Genova, Italy

    Nicolino Ruperto, Rachana Hasija, Dinara Guseinova, Giovanni Filocamo, Erkan Demirkaya & Clara Malattia

  2. IRCCS G. Gaslini, Servizio di Epidemiologia e Biostatistica, Genova, Italy

    Angela Pistorio & Alberto Martini

  3. IRCCS G. Gaslini, Pediatria II, Reumatologia e Dipartimento di Pediatria, Università degli Studi di Genova, Genova, Italy

    Angelo Ravelli & Alberto Martini

  4. IRCCS G. Gaslini, Pediatria II, Reumatologia, PRINTO, EULAR Centre of Excellence in Rheumatology 2008–2013, Largo Gaslini, 5, 16147, Genova, Italy

    Nicolino Ruperto

Authors
  1. Nicolino Ruperto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Pistorio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angelo Ravelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rachana Hasija
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dinara Guseinova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovanni Filocamo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erkan Demirkaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Clara Malattia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alberto Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Paediatric Rheumatology International Trials Organisation (PRINTO)

Corresponding author

Correspondence to Nicolino Ruperto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruperto, N., Pistorio, A., Ravelli, A. et al. Criteria to define response to therapy in paediatric rheumatic diseases. Eur J Clin Pharmacol 67 (Suppl 1), 125–131 (2011). https://doi.org/10.1007/s00228-010-0937-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-010-0937-8

Keywords

Search

Navigation