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Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial.
Ann Rheum Dis 2019; 78(1):51-59AR

Abstract

QUESTION

Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)?

METHODS

In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events.

RESULTS

94 children (67 % girls) aged median (IQR) 9.1 (4.6-12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5-12), limited joints 2.5 (1-4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3-15.0) months in arm 1, 9.0 (6.0-12.8) months in arm 2 and 9.0 (6.0-12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0-6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar.

CONCLUSION

Regardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible.

TRIAL REGISTRATION NUMBER

1574.

Authors+Show Affiliations

Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands p.hissinkmuller@lumc.nl. Department of Paediatric Rheumatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Department of Paediatrics, Alrijne Hospital Leiderdorp, Leiderdorp, The Netherlands.Department of Paediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.Department of Paediatrics, Hagaziekenhuis Juliana Children's Hospital, The Hague, The Netherlands.Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.Princess Máxima Center, Center for Pediatric Oncology, Utrecht, The Netherlands.Department of Paediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.Department of Paediatric Rheumatology, Amsterdam Rheumatology, Immunology Center Reade Amsterdam, Amsterdam, The Netherlands. Department of Paediatrics, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.Department of Paediatric Rheumatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.Department of Paediatric Hematology, Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital AMC, University of Amsterdam, Amsterdam, The Netherlands.Department of Biostatistics, Leiden University Medical Center, Leiden, The Netherlands.Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.Department of Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30309970

Citation

Hissink Muller, Petra, et al. "Treat to Target (drug-free) Inactive Disease in DMARD-naive Juvenile Idiopathic Arthritis: 24-month Clinical Outcomes of a Three-armed Randomised Trial." Annals of the Rheumatic Diseases, vol. 78, no. 1, 2019, pp. 51-59.
Hissink Muller P, Brinkman DMC, Schonenberg-Meinema D, et al. Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial. Ann Rheum Dis. 2019;78(1):51-59.
Hissink Muller, P., Brinkman, D. M. C., Schonenberg-Meinema, D., van den Bosch, W. B., Koopman-Keemink, Y., Brederije, I. C. J., ... Ten Cate, R. (2019). Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial. Annals of the Rheumatic Diseases, 78(1), pp. 51-59. doi:10.1136/annrheumdis-2018-213902.
Hissink Muller P, et al. Treat to Target (drug-free) Inactive Disease in DMARD-naive Juvenile Idiopathic Arthritis: 24-month Clinical Outcomes of a Three-armed Randomised Trial. Ann Rheum Dis. 2019;78(1):51-59. PubMed PMID: 30309970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial. AU - Hissink Muller,Petra, AU - Brinkman,Danielle M C, AU - Schonenberg-Meinema,Dieneke, AU - van den Bosch,Wytse Bastiaan, AU - Koopman-Keemink,Yvonne, AU - Brederije,Isabel C J, AU - Bekkering,Peter W, AU - Kuijpers,Taco W, AU - Van Rossum,Marion, AU - van Suijlekom-Smit,Lisette W A, AU - van den Berg,J Merlijn, AU - Boehringer,Stefan, AU - Allaart,Cornelia F, AU - Ten Cate,R, Y1 - 2018/10/11/ PY - 2018/06/08/received PY - 2018/09/11/revised PY - 2018/09/12/accepted PY - 2018/10/13/pubmed PY - 2018/10/13/medline PY - 2018/10/13/entrez KW - inactive disease KW - juvenile idiopathic arthritis KW - treatment strategy study KW - treatment-to-target SP - 51 EP - 59 JF - Annals of the rheumatic diseases JO - Ann. Rheum. Dis. VL - 78 IS - 1 N2 - QUESTION: Which is the best strategy to achieve (drug-free) inactive disease in juvenile idiopathic arthritis (JIA)? METHODS: In a randomised, single-blinded, study in disease-modifying anti-rheumatic drug (DMARD)-naive patients with JIA, three treatment-strategies were compared: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX +etanercept. Treatment-to-target entailed 3-monthly DMARD/biological adjustments in case of persistent disease activity, with drug tapering to nil in case of inactive disease.After 24 months, primary outcomes were time-to-inactive-disease and time-to-flare after DMARD discontinuation. Secondary outcomes were adapted ACRPedi30/50/70/90 scores, functional ability and adverse events. RESULTS: 94 children (67 % girls) aged median (IQR) 9.1 (4.6-12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. At baseline visual analogue scale (VAS) physician was mean 49 (SD 16) mm, VAS patient 53 (22) mm, erythrocyte sedimentation rate 12.8 (14.7), active joints median 8 (5-12), limited joints 2.5 (1-4.8) and Childhood Health Assessment Questionnaire score mean 1.0 (0.6).After 24 months, 71% (arm 1), 70% (arm 2) and 72% (arm 3) of patients had inactive disease and 45% (arm 1), 31% (arm 2) and 41% (arm 3) had drug-free inactive disease. Time-to-inactive-disease was median 9.0 (5.3-15.0) months in arm 1, 9.0 (6.0-12.8) months in arm 2 and 9.0 (6.0-12.0) months in arm 3 (p=0.30). Time-to-flare was not significantly different (overall 3.0 (3.0-6.8) months, p=0.7). Adapted ACR pedi-scores were comparably high between arms. Adverse events were similar. CONCLUSION: Regardless of initial specific treatments, after 24 months of treatment-to-target aimed at drug-free inactive disease, 71% of recent-onset patients with JIA had inactive disease (median onset 9 months) and 39% were drug free. Tightly controlled treatment-to-target is feasible. TRIAL REGISTRATION NUMBER: 1574. SN - 1468-2060 UR - https://wwww.unboundmedicine.com/medline/citation/30309970/Treat_to_target__drug_free__inactive_disease_in_DMARD_naive_juvenile_idiopathic_arthritis:_24_month_clinical_outcomes_of_a_three_armed_randomised_trial_ L2 - https://ard.bmj.com/cgi/pmidlookup?view=long&pmid=30309970 DB - PRIME DP - Unbound Medicine ER -