POS0080 TOFACITINIB TREATMENT IN CHILDREN WITH RHEUMATIC DISEASES: SINGLE-CENTER EXPERIENCE
Authors: M. Kostik, R. Raupov, E. Suspitsin, E. Isupova, T. Gabrusskaya, M. Dubko, L. Snegireva, V. Masalova, T. Ermachenkova, L. Sorokina, T. Likhacheva, M. Kaneva, E. Gaidar, O. Kalashnikova, V. Chasnyk
Journal: Annals of the Rheumatic Diseases (2021)

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 &gt; 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. # Diagnosis Indication Previous biologics Current treat-ment TOF, dose, mg/kg Duration of TOF treatment, months Genetic variants detected Efficacy 1 AID Severe inflamma-tion, aortitis, colitis INX, TCZ, ADA CS, TOF 0.5 7 NOD2 c.2578G&gt;A (p.A860T); NOD2 c.2722G&gt;C (p.G908R) ADA2 c.927G&gt;A (p.M309I) PR 2 JDM recurrent skin rash CS, TOF, MTX 0.5 5 PR 3 JDM skin involvement, ulceration CS, MTX, TOF 0.7 7 NLRP12c.154G&gt;A (p.G52S) CR 4 AID, IFP skin rash, recurrent inflammation, failure to thrive CAN, TCZ CS, TOF, CAN 0.5 32 RNASEH2B c.916dupA (p.I309Nfs*7) CR 5 JIA, poly severe arthritis ETA,TCZ, ADA TOF,TCZ 0.27 22 PR 6 soJIA resistant to CS and biologic systemic inflammation, arthritis TCZ, ABC, CAN TOF, TCZ 0.4 23 PR 7 JIA, poly (RF+) alopecia Severe arthritis, lung involvement, alopecia ETA, ABC, TCZ, ADA TOF, MTX, CS 0.3 37 IL1RN c.10G&gt;C (p.A4P); NLRP3 c.2113C&gt;A (p.Q705L); MEFV c.1105C&gt;T (p.P369S) CR 8 IFP, CANDLE- like recurrent inflammation, digital ischemia, ulcers, CS-dependency ETA, RTX, CAN TOF, CS 0.25 43 MDA5 NLRP3 CR 9 AID, IFP systemic inflammation, ulcers ETA TOF, CS 0.5 13 СR 10 JIA, ERA arthritis ETA TOF, MTX 0.2 44 CR 11 JIA, poly arthritis ABC, ETA TOF, MTX 0.25 38 CR 12 JIA, poly Arthritis, alopecia ETA TOF 0.15 31 PR 13 soJIA + MAS systemic inflammation, arthritis TCZ, CAN, ETA TOF, CS 0.5 38 NR 14 JIA, poly arthritis INX, ETA, ADA, TCZ TOF, MTX 0.2 24 PR 15 AID Systemic inflammation, CS-dependency TCZ TOF,CS 0.5 21 STAT3, c1343A&gt;C PR 16 JIA, ERA arthritis ETA TOF 0.25 21 PR 17 JIA, poly arthritis ADA, TCZ, ETA TOF 0.15 39 СR Figure 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.