POS0080 TOFACITINIB TREATMENT IN CHILDREN WITH RHEUMATIC DISEASES: SINGLE-CENTER EXPERIENCE

Autor: R. Raupov, V. Masalova, Evgeny N. Suspitsin, Vyacheslav Chasnyk, Lubov Sorokina, T. Ermachenkova, T. Likhacheva, M. Kostik, Olga Kalashnikova, T. Gabrusskaya, E. Gaidar, M. Dubko, L. Snegireva, E. Isupova, M. Kaneva
Rok vydání: 2021
Předmět:
Zdroj: Annals of the Rheumatic Diseases. 80:247.1-248
ISSN: 1468-2060
0003-4967
DOI: 10.1136/annrheumdis-2021-eular.1913
Popis: Background:While efficacy of tofacitinib (TOF) has been proven in many adult immune-mediated conditions, the information on its’ safety and efficacy in the pediatric population is limited.Objectives:to evaluate the safety and efficacy of TOF in children with immune-mediated diseases.Methods:from 23 children whom TOF has been initiated, 17 children with treatment duration of > 6 months were extracted including 16 girls and 1 boy with the following diagnosis: JIA (n=10), autoinflammatory diseases (AID) (n=5) and juvenile dermatomyositis (JDM) (n=2) due to impossibility to taper corticosteroids (CS) or previous biologic treatment failed. The treatment outcome was classified according to the opinion of the attending physicians as complete response (CR) i.e., the absence of disease activity, partial response (PR) – a significant improvement of symptoms and disease activity or no response (NR) - no changes in disease activity.Results:Mean duration of TOF treatment was 25.4±18.9 months. TOF was used as monotherapy in 3 cases, in combination with methotrexate (MTX) in 6, and in combination with other biologics in 3 children: tocilizumab (n=2) and canakinumab (n=1). Nine patients received CS. (Table 1). In two JIA patients with alopecia TOF induced intensive hair growth and controlled joint inflammation. 9 patients had CR: AID (n=3), JIA (n=4) and JDM(n=1): 7 patients had PR and 1 was NR. 13 patients had a previous history of several subsequent failed biologic: 4 biologics (n=1), 3 biologics (n=6), 2 biologics (n=1), 1 biologic (n=5). TOF treatment allowed discontinuation of CS in patient#6 and reducing the CS in 8/10 patients from 0.4 ±0.27 mg/kg to 0.15±0.1 mg/kg in 3.7±3.4 times: in 2 cases the tapering of steroids failed (Figure 1). 4 patients had side effects not requiring treatment discontinuation: liver enzymes elevation (n=2), hypercholesterolemia (n=1), lymphadenitis (n=1). In pt#6 after achievement of the remission the TOF dosage was decreased up to 2 times and tocilizumab intervals were increased up to 6 weeks.Table 1.#DiagnosisIndicationPrevious biologicsCurrent treat-mentTOF, dose, mg/kgDurationof TOF treatment, monthsGeneticvariantsdetectedEfficacy1AIDSevere inflamma-tion, aortitis, colitisINX, TCZ, ADACS, TOF0.57NOD2 c.2578G>A (p.A860T); NOD2 c.2722G>C (p.G908R)ADA2 c.927G>A (p.M309I)PR2JDMrecurrent skin rashCS, TOF, MTX0.55PR3JDMskin involvement, ulcerationCS, MTX, TOF0.77NLRP12c.154G>A (p.G52S)CR4AID,IFPskin rash, recurrent inflammation, failure to thriveCAN, TCZCS, TOF, CAN0.532RNASEH2Bc.916dupA (p.I309Nfs*7)CR5JIA,polysevere arthritisETA,TCZ, ADATOF,TCZ0.2722PR6soJIAresistant to CS and biologic systemic inflammation, arthritisTCZ, ABC, CANTOF, TCZ0.423PR7JIA,poly (RF+) alopeciaSevere arthritis, lung involvement,alopeciaETA, ABC, TCZ, ADATOF, MTX, CS0.337IL1RN c.10G>C (p.A4P); NLRP3 c.2113C>A (p.Q705L); MEFV c.1105C>T (p.P369S)CR8IFP, CANDLE-likerecurrent inflammation, digital ischemia, ulcers, CS-dependencyETA, RTX, CANTOF, CS0.2543MDA5NLRP3CR9AID, IFPsystemic inflammation, ulcersETATOF, CS0.513СR10JIA, ERAarthritisETATOF, MTX0.244CR11JIA, polyarthritisABC, ETATOF, MTX0.2538CR12JIA, polyArthritis, alopeciaETATOF0.1531PR13soJIA + MASsystemic inflammation, arthritisTCZ, CAN, ETATOF, CS0.538NR14JIA, polyarthritisINX, ETA, ADA, TCZTOF, MTX0.224PR15AIDSystemic inflammation, CS-dependencyTCZTOF,CS0.521STAT3, c1343A>CPR16JIA, ERAarthritisETATOF0.2521PR17JIA, polyarthritisADA, TCZ, ETATOF0.1539СRFigure 1.Conclusion:Tofacitinib is a promising agent in treating pediatric rheumatic diseases. In our study the best results were in AID patients with rare alleles in interferon pathway genes, patients with arthritis and alopecia and in children with JDM. Future studies are needed to identify clear indications for treatment with JAK-inhibitors.Acknowledgements:This work was supported by the RSF grant №20-45-01005.Disclosure of Interests:None declared.
Databáze: OpenAIRE
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