The Safety and Efficacy of Tofacitinib in 24 Cases of Pediatric Rheumatic Diseases: Single Centre Experience

Mikhail M Kostik; Rinat K Raupov; Evgeny N Suspitsin; Eugenia A Isupova; Ekaterina V Gaidar; Tatyana V Gabrusskaya; Maria A Kaneva; Ludmila S Snegireva; Tatyana S Likhacheva; Rimma S Miulkidzhan; Artem V Kosmin; Anastasia V Tumakova; Vera V Masalova; Margarita F Dubko; Olga V Kalashnikova; Ivona Aksentijevich; Vyacheslav G Chasnyk

doi:10.3389/fped.2022.820586

The Safety and Efficacy of Tofacitinib in 24 Cases of Pediatric Rheumatic Diseases: Single Centre Experience

Front Pediatr. 2022 Feb 8:10:820586. doi: 10.3389/fped.2022.820586. eCollection 2022.

Authors

Mikhail M Kostik¹, Rinat K Raupov^{1

2}, Evgeny N Suspitsin^{1

3}, Eugenia A Isupova¹, Ekaterina V Gaidar¹, Tatyana V Gabrusskaya¹, Maria A Kaneva¹, Ludmila S Snegireva¹, Tatyana S Likhacheva¹, Rimma S Miulkidzhan³, Artem V Kosmin³, Anastasia V Tumakova¹, Vera V Masalova¹, Margarita F Dubko¹, Olga V Kalashnikova¹, Ivona Aksentijevich⁴, Vyacheslav G Chasnyk¹

Affiliations

¹ Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russia.
² Saint Petersburg State Health Care Establishment the City Hospital No 40 of the Resort District, Saint-Petersburg, Russia.
³ Laboratory of the Molecular Oncology, N.N. Petrov's Institute of Oncology, Saint-Petersburg, Russia.
⁴ Inflammatory Disease Section, National Human Genome Research Institute, Bethesda, MD, United States.

Abstract

JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA).

Aim of study: To evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.

Material and methods: We extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)-a significant improvement of symptoms and disease activity, or no response (NR)-no changes in disease activity.

Results: CR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1).

Conclusion: JAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.

Keywords: JAK-inhibitors; alopecia; interferon type-I; interferonopathy; juvenile dermatomyositis; juvenile idiopathic arthritis; tofacitinib.