NextGen 2024: Weaning meds when disease is controlled Session Part 1
NextGen 2024: Weaning meds when disease is controlled Session Part 1
- The Utrecht protocol uses rIL-1RA as a first-line treatment for new-onset Systemic Juvenile Idiopathic Arthritis (SJIA) and is effective in a national multicenter setting.
- Adding IL-18 as a biomarker (with a cutoff value of 1200 pg/mL) improves the success of tapering rIL-1RA in SJIA patients achieving Clinical Inactive Disease (CID) at 3 months with rIL-1RA monotherapy.
- Early tapering and stopping reduces the treatment duration and amount of injections.
- Biological treatments targeting IL1 (anakinra, canakinumab) and IL6 (tocilizumab) pathways show improved prognosis and reduce the need for steroids, though potential side effects include osteoporosis, slowed growth, and increased risk of infections.
NextGen 2024: Weaning meds when disease is controlled Session Part 1
@SJIA_Foundation3 months ago

Biomarker-Guided Treatment-And-Stop-Strategy for Recombinant IL-1Receptor Antagonist (anakinra) in Systemic Juvenile Idiopathic Arthritis
Bas Vastert, MD, PhD
Head of the department of pediatric rheumatology and immunology, Wilhelmina Children's Hospital Center for Translational Immunology, UMC Utrecht
- · Biological treatment targeting the IL1 (anakinra, canakinumab) and IL6 (tocilizumab) pathway
- · Improved prognosis and reduced need for steroids
- · Side-effects in children: osteoporosis, slowed growth, increased risk of infections, increased blood pressure, increased blood sugar, mood changes, cataract and cushingoid appearance (moon-face)
- · Biologicals are more effective when started early in the disease (Window of opportunity) 2
- · CID after 3 months of rIL-1RA mono-therapy
- · National multicenter setting = historic single center cohort
- · 73% vs. 71%
- · 45 patients entered the intervention cohort
- · 40: IL-18 under threshold within intervention time-frame
- · 80% success without restart
- · 4: IL-18 > threshold until t=8 months
- · 50% success without restart
- · Overall IL-18 with a cutoff of 1200pg/ml in the protocol significantly increases the percentage of patients with a successful taper-and-stop 1 year after rIL-1RA mono-therapy initiation compared to the historic cohort
- · 76% vs. 47% p=0.03
- · 97% of successful taper-and stop remains in remission up to 24 months
- · The Utrecht protocol, starting rIL-1RA early as first-line treatment in new-onset SJIA, is highly effective, also in a national multicenter setting
- · The addition of IL-18 with a cut-off value of 1200 pg/mL as a biomarker significantly increases the success of a tapering strategy of rIL-1RA in patients achieving CID at 3 months on rIL-1RA mono-therapy
- · Early taper and stop reduces the duration of treatment and amount of injections necessary
- · Our study also provide important information on the disease-course of non-mono phasic patients, with a higher chance for refractory disease
- UMC Utrecht · The down slope of IL-18 in the first months after treatment is associated with and predictive of refractory disease
- · Incidence of MAS seems not reduced!
- · 17% (11/66) of patients developed MAS in the follow-up of ESTIS
- · >50% in the first 3 months after start of treatment
sJIA treatment



Utrecht protocol

Study design ESTIS

Cohort characteristics
Baseline cohort characteristics
Total number of participants
66
Number of participants intervention phase
45
Percentage of females (n)
54.6% (36/66)
Median age at start of symptoms in years (range)
8.86 (0.84- 15.71)
Trisomy 21
1/66 8.97 (0.93-16.61)
Median age at start of anakinra in years (range)
Median days onset symptoms to start anakinra (IQR)
23 (13-44)
Median Anakinra starting dose in mg/kg (range)
2 (1-5)
+/- 30% of patients without arthritis at start of rIL-1RA comparable to Ter Haar et al. A&R 2019

Improved taper-and-stop strategy

Conclusions

2

IL-18 Levels at Baseline and 3 Months
Baseline Wilcoxon p-value: 0.679
3 Months Wilcoxon p-value: 0.159

2
20000
15000
5000
100
200
300
400
Days after start anakinra
Non-linear mixed effects modeling
AMCO3-001
AMCO3-003
AMCO3-004
AMCO3-006
AMCO3-007
2
20000
15000
10000
5000
Days after start anakinra
400
Cytokine modeling

Macrophage Activation Syndrome


Remco Erkens









Acknowledgements
Dieneke Schonenberg-Meinema


Erika v Nieuwenhove
Dörte Hamann
Thomas Vogl
Sytze De Roock
Marc Jansen
Discussion

Anakinra side-effects: Local reaction at injection site (redness, itching) generally, appear within 2 weeks of therapy, disappear within 4-6 weeks (transient) liver enzyme elevations Potential increased risk of infections (mainly respiratory) Allergic reactions (anaphylaxis)



















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