Tofacitinib bested placebo for disease flares in polyarticular JIA
ATLANTA — Results of a double-blind, randomized, placebo-controlled trial showed a clear benefit of tofacitinib in controlling disease flares in juvenile idiopathic arthritis, according to a speaker at ACR/ARP 2019.
Hermine Brunner, MD, MSc, director of the division of rheumatology at Cincinnati Children’s Hospital Medical Center, addressed the need for novel therapies in JIA, particularly those that can be ingested orally, in an interview with Healio Rheumatology. “The oral formulation is appealing to children because currently available advanced medications for children with JIA are injectable or require infusion,” she said. “Children are happy to have an oral medication that is similarly effective as those treatments.”
The phase 3 withdrawal study included patients aged 2 to younger than 18 years with polyarticular course JIA, psoriatic arthritis or enthesitis-related arthritis. Protocols called for an 18-week open-label run-in phase in which patients received active therapy until reaching ACR30 response. Patients were then randomly assigned oral tofacitinib (Xeljanz, Pfizer) or placebo twice a day. Dosing was based on body weight.
“We wanted to limit the amount of time children were receiving placebo,” Brunner said.
She noted that the drug comes in tablet form, or in a solution that tastes like grape juice. Disease flare at week 44, or week 26 of the second phase of the study, served as the primary outcome measure. Secondary endpoints included JIA ACR50/30/70 response rates and change from baseline in Childhood Health Assessment Questionnaire Disability Index by week 44. The researchers also assessed for safety outcomes.
Results showed that 185 patients completed the first phase of the study, at which point 88 patients were assigned tofacitinib and 85 were assigned placebo. Ultimately, 61 patients in the tofacitinib arm and 38 patients in the placebo arm completed the trial.
Primary endpoint results showed that 52.9% of patients in the placebo arm, compared with just 29.2% of those assigned tofacitinib, experienced a disease flare (P = .0041). Brunner noted that this nearly cut the risk in half (HR =0.459; 95% CI, 0.268, 0.785).
“We were not surprised by this result,” Brunner said, adding that the effects of tofacitinib, even from the first phase of the study, carried for quite some time. “It took about 40 days for the placebo and tofacitinib curves to separate in terms of flare events. There is the pharmacological half-life of the drug, but the immune response is much longer.”
Tofacitinib also yielded improvements in ACR30 (70.8% vs. 47.1%; P = .0031), ACR50 (66.7% vs. 47.1%; P = .0166), and ACR70 (54.2% vs. 37.1%; P = .0387) response.
“All of these results are pretty astounding,” Brunner said of the durability of tofacitinib effect. “It is a testament to the acceptability of this study design in pediatric patients.”
Safety data showed one serious adverse event each in the tofacitinib and placebo groups in the second phase of the study. “Serious side effects were rare, and there were no deaths,” Brunner said. “Nobody developed tuberculosis or a malignancy.” – by Rob Volansky
Brunner H. Abstract #L22. Tofacitinib for the treatment of polyarticular course juvenile idiopathic arthritis: results of a phase 3 randomized, double-blind, placebo-controlled withdrawal study. Presented at ACR/ARP Annual Meeting; Nov. 9-13, 2019; Atlanta.
Disclosure: Brunner reports receiving research grants from BMS, MedImmune, Novartis and Pfizer Inc; being an employee of CCMHC; receiving consulting fees or other remuneration from AbbVie, AstraZeneca-MedImmune, Bayer, Biocon, BMS, Boehringer-Ingelheim, Janssen, Eli Lilly, Novartis, Pfizer Inc, R-Pharm, and Roche; and is a member of speakers’ bureaus for GSK, Novartis, and Roche.