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Tofacitinib Not Superior to Placebo in Systemic Juvenile Arthritis Double-Blind Trial
However, fewer patients experienced flares in the tofacitinib group than in the placebo group, among other positive findings.
Tofacitinib did not statistically significant prolong time to systemic juvenile idiopathic arthritis (sJIA) disease flare in a double-blind (DB) study compared to placebo, however, improvements in disease activity were seen during the open-label (OL) phase.1
These findings, from a phase 3, randomized, withdrawal study (NCT03000439), were presented by Hermine Brunner, MD, MDc, MBA, Director, Division of Rheumatology, and professor, Department of Pediatrics, Cincinnati Children’s at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC.
“What we did see is that the medication was well tolerated, and based on the OL part, it has, in my mind, at least some therapeutic benefit for a subset of patients with sJIA,” Brunner told HCPLive® during the meeting.
The study consisted of an OL phase and a DB phase. In part 1 of the OL phase, patienst received tofacitinib 5 mg twice daily or equivalent weight-based dose and had 16 weeks to achieve and maintain an adapted JIA-ACR30 response for at least 4 weeks before proceeding to the second OL part, in which patients treated with over 0.2 mg/kg/day corticosteroids attempted to taper while maintaining clinical response. Participants who responded to both stages were then able to enter the DB phase and were randomized to either continue tofacitinib or switch to placebo. The primary endpoint was time to sJIA disease flare in the DB phase. These reported data are from a prespecified interim analysis performed after 28 participants reported an sJIA flare in the DB phase.
Brunner and colleagues enrolled 100 pediatric participants from members of the PRINTO/PRCSG networks, 59 of which were randomized into the DB phase (28 receiving tofacitinib and 31 receiving placebo). The study did not meet its primary objective of statistically significantly prolonging time to sJIA disease flare compared with placebo in the DB phase (hazard rate, 0.633 [95% CI, 0.296-1.354]; 1-sided P = .1171) and thus the prespecified futility stopping criterion was met.1
The investigators did find that fewer patients in the tofacitinib group experienced flares (n = 11; 39.3%) than those in the placebo group (n = 17; 54.8%). The median time to flare was 295 days in the placebo group and could not be calculated for the tofacitinib group as less than half of patients had a flare.1
During the first part of the OL phase, aJIA-ACR30/70/90 responses were reached by 71 (86.6%), 28 (34.1%) and 15 (18.3%) participants at week 8. Clinically meaningful improvements in CHAQ-DI and JADAS-27 CRP were also reported. During corticosteroid taper in part 2, responses were generally maintained, with 38 participants (70.4%) achieving tapering criteria.1
At DB randomization, investigators observed imbalances in disease activity, with a greater proportion of patients with JADAS-27 CRP inactive disease and aJIA-ACR100 responses randomized to placebo compared with those randomized to tofacitinib. The tofacitinib group generally maintained efficacy on JADAS-27 CRP and aJIA-ACR100 outcomes during the DB phase. The frequency of treatment‑emergent (TE) adverse events (AEs) was also similar between groups during this phase with no severe/serious AEs reported in the tofacitinb group. Notably, there were a greater number of sJIA flare TEAEs in the placebo group (n = 14; 45.2%) than the tofacitinib group (n = 8; 28.6%), which led to higher rates pf TEAEs leading to discontinuation in the placebo group.1
“There is an unclear understanding what the interplay is between the currently approved medication and the development of interstitial lung disease (ILD). There are some groups who say, based on the scientific evidence, it's not the medication, we see the lung disease because the patients survive. But there are some of the opinion that these medications are dangerous, and one could argue that a different class of medications that are not biologics, such as a JAK inhibitor, or another small molecule, could actually help to provide another therapeutic option for these children,” Brunner said.
The role of biologics in the development of ILD was definitely a big topic during the meeting, as some studies have shown higher rates of ILD in patients with RA and PsA initiating biologics.2
