“Our patients and parents have been waiting for oral alternatives to injectable drugs and the JAK inhibitors have come at the right time,” Prof. Athimalaipet Ramanan (Bristol Medical School, UK) expressed as he reported on the phase 3 JUVE-BASIS trial (NCT03773978) of baricitinib in juvenile idiopathic arthritis (JIA) with an unusual design1. “All patients, in order to be ethical and also not to subject our paediatric patients to placebo, were given access to the drug, and, at 12 weeks, the responders were randomised on a 1 to 1 basis to either continue the drug or switch to placebo,” Prof. Ramanan explained. The double-blind withdrawal period extended from week 12 through 44 and the primary endpoint was the time to disease flare. Enrolled JIA patients (n=220) had to be between 2 and 18 years while having a history of inadequate response to conventional synthetic or biologic disease-modifying antirheumatic drugs (cs or bDMARD).
At baseline, the mean age of the participants was 13.3 years and the mean disease duration was 4 years. Of the 220 participants, 52.7% had already been treated with biologics, 57.7% were on methotrexate, and 32.7% on corticosteroids. After the lead-in, JIA-ACR30 responses were reached by 76.3%, with corresponding rates for JIA-ACR50 at 63.5%, JIA-ACR70 at 46.1%, and JIA-ACR90 at 20.1%. “But the key was really in the withdrawal phase,” Prof. Ramanan stressed. Of the patients who stayed on baricitinib, 17.1% had a flare compared with 50.6% in the group that was switched to placebo (P<0.001). “Not only do those who get switched to placebo have a higher incidence of flaring, but they were also more likely to flare quickly (as quickly as 4 weeks),” Prof. Ramanan commented on this significant result in the primary endpoint with a hazard ratio of 0.241 (P<0.001) in favour of baricitinib.
In weeks 0–12, the discontinuation rate due to adverse events (AE) was 0.9%. During the withdrawal part, 2 participants in the placebo and 1 participant in the baricitinib arm ended the trial because of AE. From weeks 12–44, treatment-emergent AEs were observed in 46.9% of placebo and 65.9% of baricitinib participants. Serious AEs occurred in 3.7% (placebo) and 4.9% (baricitinib) of participants. All in all, the researchers valued the safety results as consistent with the known safety profile of baricitinib.
These findings support baricitinib, an oral JAK1/2 agent, as an alternative treatment for JIA patients with an inadequate response to cs or bDMARD. “These are very interesting findings for our patients and parents of children with JIA,” Prof. Ramanan interpreted the trial results.
Reference:
1. Ramanan AV, et al. Baricitinib in juvenile idiopathic arthritis: a phase 3, double-blind, placebo-controlled, withdrawal, efficacy and safety study. LB0002, EULAR 2022, Copenhagen, 1-4 June, Copenhagen, Denmark.