Tofacitinib Yields Rapid and Sustained Improvement in Juvenile Idiopathic Arthritis

By Reuters Staff

November 29, 2021

NEW YORK (Reuters Health) - Tofacitinib significantly reduces the number of flares in children with polyarticular course juvenile idiopathic arthritis (JIA), according to the first phase-3 clinical trial to assess the efficacy of a Janus kinase (JAK) inhibitor in JIA.

JIA is a heterogeneous group of chronic conditions with no known cause that develop before age 16 years, the study team explains in The Lancet.

"Per current recommendations, patients with the most severe forms, polyarticular course JIA and systemic JIA, are treated with conventional synthetic and biological disease-modifying antirheumatic drugs (DMARDs), which have considerably improved long-term outcomes over the past 30 years," note Dr. Nicolino Ruperto of IRCCS Istituto Giannina Gaslini, in Genova, Italy, and colleagues.

In their study, tofacitinib led to "rapid and sustained clinical improvement in polyarticular course JIA disease activity with no new potential safety risks identified," they report.

The study enrolled 225 children (mean age, 13 years; 75% female) with polyarticular course JIA from 64 centers in 14 countries. Most patients (65%) received concomitant methotrexate.

During the first part of the study, patients received oral, open-label tofacitinib in doses based on weight (5 mg twice daily or lower) for 18 weeks. Patients with at least JIA/ACR 30 response were then randomly allocated to continue tofacitinib (72 patients) or switch to placebo (70 patients) for 26 weeks. The primary endpoint of the study was JIA flare rate by 44 weeks during the second part of the study.

The rate of JIA flare was significantly lower in patients treated with tofacitinib (29% vs. 53%; hazard ratio, 0.46; 95% confidence interval: 0.27 to 0.79).

"There were no new potential safety risks identified for tofacitinib in children and adolescents. Indeed, overall, safety was consistent with that previously reported in patients with rheumatoid arthritis," the researchers report.

Adverse events occurred in 77% of patients treated with tofacitinib and 74% treated with placebo, and serious adverse events occurred in 1% and 2%, respectively.

The most common adverse events were upper-respiratory-tract infections (15%), disease progression (6%), and JIA exacerbation (4%). Over the entire tofacitinib exposure period, 107 of 225 patients (48%) developed infections or infestations. No deaths occurred.

The findings "suggest a favorable benefit-risk balance in patients with polyarticular course JIA treated with oral tofacitinib," the study team concludes.

The authors of a linked comment say an important consideration is that the study excluded patients with active uveitis within three months of enrollment and included only one patient with a history of inactive uveitis.

"Uveitis is the most common and potentially serious extra-articular manifestation of JIA. It affects between 12% and 30% of patients and is a considerable cause of JIA-associated morbidity. Thus, evidence of the effect of tofacitinib on uveitis incidence or activity ... would be important in informing real-world treatment choices, both in polyarticular course JIA and more broadly," write Dr. Sarah Clarke and Dr. Athimalapiet Ramanan with Bristol Royal Hospital for Children in the U.K.

"The inclusion of patients with JIA-associated uveitis in pediatric investigation or study plans would greatly aid in addressing this issue," they add.

"Despite its limitations, the trial by Ruperto and colleagues represents an important step in the treatment of JIA by providing the first indications of the efficacy of tofacitinib in JIA and addressing the need for a globally accessible, oral therapy," the editorial writers conclude.

The study was funded by Pfizer. Several authors have disclosed financial relationships with the company.

SOURCE: and The Lancet, online November 9, 2021.