Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial

Ruperto, Nicolino; Brunner, Hermine I.; Synoverska, Olga; Ting, Tracy V.; Mendoza, Carlos Abud; Spindler, Alberto; Vyzhga, Yulia; Marzan, Katherine; Grebenkina, Lyudmila; Tirosh, Irit; Imundo, Lisa F.; Jerath, Rita; Kingsbury, Daniel J.; Sözeri, Betül; Vora, Sheetal S.; Prahalad, Sampath; Жолобова, Елена; Aviel, Yonatan Butbul; Chasnyk, Vyacheslav; Lerman, Melissa A.; Nanda, Kabita; Schmeling, Heinrike; Tory, Heather; Uziel, Yosef; Viola, Diego Oscar; Posner, Holly; Kanik, Keith S.; Wouters, Ann; Chang, Cheng; Zhang, Richard; Lazariciu, Irina; Hsu, Ming‐Ann; Suehiro, Ricardo Maisse; Martini, Alberto; Lovell, Daniel J.

doi:10.1016/s0140-6736(21)01255-1

Cited by 114 publications

(53 citation statements)

References 24 publications

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“…Adverse events were observed in 153/225 (68%) children with JIA receiving tofacitinib, while serious adverse events were registered in seven patients. Discontinuations due to adverse events required 26 patients to discontinue this treatment in 26 (11.6%) ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…In case of infection, the discontinuation of tofacitinib leads to rapid wash-out of medication from the blood ( 41 ). Other benefits for children who are destined for life-long therapies, include the lack of immunogenicity and oral administration ( 9 , 42 ). We have to note about potential significant risks of using JAK inhibitors in combination with biologics and about the potential risks of using tofacitinib dose greater than 5mg two times a day.…”

Section: Discussionmentioning

confidence: 99%

“…The success of the use of kinases-blockers in oncology ( 4 ) has paved the way for the use of JAK-inhibitors in rheumatic diseases, especially in rheumatoid arthritis: ruxolitinib ( 5 ), tofacitinib ( 6 ) and baricitinib ( 7 ). Food and Drug Administration (FDA) has approved tofacitinib for the treatment of rheumatoid arthritis ( 8 ), psoriatic arthritis, ulcerative colitis, and since 2020 for polyarticular juvenile idiopathic arthritis 1 There are data from RCT in JIA available ( 9 ). Clinical trials of JAK-inhibitors for systemic lupus erythematosus, dermatomyositis, alopecia areata, atopic dermatitis, Crohn's disease, and uveitis are still ongoing ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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 StudyTo evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.Material and MethodsWe 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.ResultsCR 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).ConclusionJAK-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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Synthetic DMARDs, such as Janus Kinase (JAK) inhibitors, are emerging as promising treatments for adult PsA ( 60 , 61 ); recently, tofacitinib, already used for adults, has been approved for JIA and JPsA ( 62 ).…”

Section: Treatmentmentioning

confidence: 99%

New Insights on Juvenile Psoriatic Arthritis

et al. 2022

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Juvenile psoriatic arthritis (JPsA) is a relatively rare condition in childhood as it represents approximately 5% of the whole Juvenile Idiopathic Arthritis (JIA) population. According to International League of Associations of Rheumatology (ILAR) classification, JPsA is defined by the association of arthritis and psoriasis or, in the absence of typical psoriatic lesions, with at least two of the following: dactylitis, nail pitting, onycholysis or family history of psoriasis in a first-degree relative. However, recent studies have shown that this classification system could conceal more homogeneous subgroups of patients differing by age of onset, clinical characteristics and prognosis. Little is known about genetic factors and pathogenetic mechanisms which distinguish JPsA from other JIA subtypes or from isolated psoriasis without joint involvement, especially in the pediatric population. Specific clinical trials testing the efficacy of biological agents are lacking for JPsA, while in recent years novel therapeutic agents are emerging in adults. In this review, we summarize the clinical features and the current evidence on pathogenesis and therapeutic options for JPsA in order to provide a comprehensive overview on the clinical management of this complex and overlapping entity in childhood.

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“…Recently tofacitinib has been approved by the Food and Drug Administration for use in JIA patients 12 . A Phase 3 randomized double‐blind placebo‐controlled study showed significant improvement in signs and symptoms, physical functioning, fewer disease flares and sustained clinical improvement 13 …”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of tofacitinib in the treatment of refractory cases of polyarticular course juvenile idiopathic arthritis: A study from Bangladesh

2022

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Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic illness in children and is a very important cause of short-and long-term morbidity and disability. 1 Worldwide incidence of JIA ranges from 0.8 to 22.6 per 100 000 children per year with the prevalence ranging from 7 to 401 per 100 000 children. 2 The exact incidence and prevalence of JIA data is not available in our country (Bangladesh). A pilot study carried out in a semi-urban area of Bangladesh showed prevalence of JIA as 60.5 per 100 000. 3

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Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial

Cited by 114 publications

References 24 publications

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

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

New Insights on Juvenile Psoriatic Arthritis

Efficacy and safety of tofacitinib in the treatment of refractory cases of polyarticular course juvenile idiopathic arthritis: A study from Bangladesh

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