Arthritis und Rheuma 2024; 44(06): 396-404
DOI: 10.1055/a-2405-1770
Schwerpunkt

Medikamentöse Absetzstrategien in der Kinderrheumatologie

Kirsten Minden
1   Deutsches Rheuma-Forschungszentrum Berlin, Programmbereich Epidemiologie und Versorgungsforschung
2   Charité Universitätsmedizin Berlin, Klinik für Pädiatrie mit SP Pneumologie, Immunologie und Intensivmedizin
3   Deutsches Zentrum für Kinder- und Jugendgesundheit, Standort Berlin
› Author Affiliations

ZUSAMMENFASSUNG

Die Prognose der juvenilen idiopathischen Arthritis (JIA) hat sich durch die Anwendung neuer Therapiestrategien und moderner Antirheumatika erheblich verbessert. Viele Patienten erreichen heute eine langanhaltende Remission, was die Frage nach einem möglichen Absetzen der Therapie aufwirft. In der klinischen Praxis variiert das Vorgehen beim Absetzen von krankheitsmodifizierenden Antirheumatika erheblich. Dabei spielen Faktoren wie die spezifische Form der JIA, das initiale Therapieansprechen, das Vorhandensein von Krankheitsschäden sowie die Präferenzen von Patienten und Familien eine Rolle. Dieser Übersichtsbeitrag stellt die aktuelle Evidenz zur Therapiedeeskalation bei der JIA vor. Es werden relevante Studien und Prädiktoren für ein erfolgreiches Absetzen der Therapie diskutiert. Zudem werden Strategien zur Erreichung einer medikamentenfreien Remission erörtert, einschließlich der potenziellen Rolle von Biomarkern und bildgebenden Verfahren. Basierend auf den vorhandenen, wenngleich noch begrenzten, Erkenntnissen werden Hinweise für den klinischen Alltag formuliert.



Publication History

Article published online:
09 December 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • Literatur

  • 1 Nguyen K, Barsalou J, Basodan D. et al A decade of progress in juvenile idiopathic athritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry. Rheumatology (Oxford). 2023; Doi: 10.1093/rheumatology/kead560
  • 2 Minden K, Horneff G, Niewerth M. 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 (Hoboken) 2019; 71: 471-481
  • 3 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: 819-828
  • 4 Halyabar O, Mehta J, Ringold S. et al Treatment Withdrawal Following Remission in Juvenile Idiopathic Arthritis: A Systematic Review of the Literature. Paediatr Drugs 2019; 21: 469-492
  • 5 Chang MH, Bocharnikov AV, Case SM. et al Joint-Specific Memory and Sustained Risk for New Joint Accumulation in Autoimmune Arthritis. Arthritis Rheumatol 2022; 74: 1851-1858
  • 6 Klotsche J, Minden K, Niewerth M. et al 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: 996-1002
  • 7 Klotsche J, Klein A, Niewerth M. et al Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis. Arthritis Res Ther 2021; 23: 118
  • 8 Horton DB, Onel KB, Beukelman T. et al 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: 352-360
  • 9 Shenoi S, Nanda K, Schulert GS. et al Physician practices for withdrawal of medications in inactive systemic juvenile arthritis, Childhood Arthritis and Rheumatology Research Alliance (CARRA) survey. Pediatr Rheumatol Online J 2019; 17: 48
  • 10 Ebato T, Kishi T, Akamine K. et al Evaluation of Medication Withdrawal in Patients with Non-systemic Juvenile Idiopathic Arthritis in Japan Using a Web-based Survey. Mod Rheumatol 2024;
  • 11 Currie GR, Groothuis-Oudshoorn CGM, Twilt M. et al What matters most to pediatric rheumatologists in deciding whether to discontinue biologics in a child with juvenile idiopathic arthritis? A best-worst scaling survey. Clin Rheumatol 2023; 42: 2173-2180
  • 12 Horton DB, Salas J, Wec A. et al Making Decisions About Stopping Medicines for Well-Controlled Juvenile Idiopathic Arthritis: A Mixed-Methods Study of Patients and Caregivers. Arthritis Care Res (Hoboken) 2021; 73: 374-385
  • 13 Guzman J, Oen K, Huber AM. et al The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort. Ann Rheum Dis 2016; 75: 1092-1098
  • 14 Lovell DJ, Johnson AL, Huang B. et al Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease. Arthritis Rheumatol 2018; 70: 1508-1518
  • 15 Kearsley-Fleet L, Baildam E, Beresford MW. et al Successful stopping of biologic therapy for remission in children and young people with juvenile idiopathic arthritis. Rheumatology (Oxford) 2023; 62: 1926-1935
  • 16 Su Y, Yang YH, Chiang BL. Treatment response to etanercept in methotrexate refractory juvenile idiopathic arthritis: an analysis of predictors and long-term outcomes. Clin Rheumatol 2017; 36: 1997-2004
  • 17 Simonini G, Bracaglia C, Cattalini M. et al Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis. J Rheumatol 2017; 44: 822-826
  • 18 Foell D, Wulffraat N, Wedderburn LR. et al Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA 2010; 303: 1266-1273
  • 19 Kalinina Ayuso V, van de Winkel EL, Rothova A. et al Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis. Am J Ophthalmol 2011; 151: 217-222
  • 20 Gerss J, Roth J, Holzinger D. et al Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study. Ann Rheum Dis 2012; 71: 1991-1997
  • 21 Hinze CH, Foell D, Johnson AL. et al Serum S100A8/A9 and S100A12 Levels in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis: Relationship to Maintenance of Clinically Inactive Disease During Anti-Tumor Necrosis Factor Therapy and Occurrence of Disease Flare After Discontinuation of Therapy. Arthritis Rheumatol 2019; 71: 451-459
  • 22 Mor-Vaknin N, Rivas M, Legendre M. et al High Levels of DEK Autoantibodies in Sera of Patients With Polyarticular Juvenile Idiopathic Arthritis and With Early Disease Flares Following Cessation of Anti-Tumor Necrosis Factor Therapy. Arthritis Rheumatol 2018; 70: 594-605
  • 23 Gul H, Di Matteo A, Anioke I. et al Predicting Flare in Patients With Rheumatoid Arthritis in Biologic Induced Remission, on Tapering, and on Stable Therapy. ACR Open Rheumatol 2024; 6: 294-303
  • 24 Nguyen H, Ruyssen-Witrand A, Gandjbakhch F. et al Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis. Rheumatology (Oxford) 2014; 53: 2110-2118
  • 25 De Lucia O, Giani T, Caporali R. et al Ultrasound versus physical examination in predicting disease flare in children with juvenile idiopathic arthritis: a systematic literature review and qualitative synthesis. Med Ultrason 2022; 24: 473-478
  • 26 Mazzoni M, Pistorio A, Magnaguagno F. et al Predictive Value of Magnetic Resonance Imaging in Patients With Juvenile Idiopathic Arthritis in Clinical Remission. Arthritis Care Res (Hoboken) 2023; 75: 198-205
  • 27 Gieling J, van den Bemt B, Hoppenreijs E. et al Discontinuation of biologic DMARDs in non-systemic JIA patients: a scoping review of relapse rates and associated factors. Pediatr Rheumatol Online J 2022; 20: 109
  • 28 Florax AA, Doeleman MJH, de Roock S. et al Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis. Rheumatology (Oxford) 2023;
  • 29 Cai Y, Liu X, Zhang W. et al Clinical trial of etanercept tapering in juvenile idiopathic arthritis during remission. Rheumatol Int 2013; 33: 2277-2282
  • 30 Braverman G, Bridges SL, Moreland LW. Tapering biologic DMARDs in rheumatoid arthritis. Curr Opin Pharmacol 2022; 67: 102308
  • 31 Hinze CH, Holzinger D, Lainka E. et al Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany. Pediatr Rheumatol Online J 2018; 16: 7
  • 32 Ter Haar NM, van Dijkhuizen EHP, Swart JF. et al Treatment to Target Using Recombinant Interleukin-1 Receptor Antagonist as First-Line Monotherapy in New-Onset Systemic Juvenile Idiopathic Arthritis: Results From a Five-Year Follow-Up Study. Arthritis Rheumatol 2019; 71: 1163-1173
  • 33 Quartier P, Alexeeva E, Constantin T. et al Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study. Arthritis Rheumatol 2021; 73: 336-346
  • 34 Teh KL, Das L, Book YX. et al Anti-tumor necrosis factor (aTNF) weaning strategy in juvenile idiopathic arthritis (JIA): does duration matter?. Clin Rheumatol 2024; 43: 1723-1733
  • 35 Chang CY, Meyer RM, 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: 658-666
  • 36 Gerss J, Tedy M, Klein A. et al Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis: results from the PREVENT-JIA trial. Ann Rheum Dis 2022; 81: 990-997
  • 37 Mandl P, Aletaha D. The role of ultrasound and magnetic resonance imaging for treat to target in rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford) 2019; 58: 2091-2098
  • 38 Ringold S, Dennos AC, Kimura Y. et al Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry. Arthritis Care Res (Hoboken) 2023; 75: 715-723
  • 39 Muller PH, 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: 51-59
  • 40 Otten MH, Prince FH, Armbrust W. et al Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. JAMA 2011; 306: 2340-2347