A Randomized Phase 2b Study of ABT-494, a Selective JAK Inhibitor in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate
This dose-ranging study evaluated the efficacy of the novel, selective JAK1 inhibitor ABT-494 versus placebo in patients with moderate-to-severe RA and inadequate response (IR) to MTX.
In this 12-week, randomised, double-blind study (BALANCE II), the efficacy and safety of
ABT-494 dosed at 3mg, 6 mg, 12 mg, 18 mg (all twice daily) and 24 mg (once daily) was assessed. Patients included had not received prior biologic therapy.
Of the 299 patients included in the analysis, the proportions of patients achieving the primary efficacy endpoint, ACR20 response at Week 12, was significantly higher with
ABT-494 than placebo for all doses except 3 mg. A significant dose-response relationship was identified for all doses (P<0.01). The onset of action was rapid, with significant difference in ACR20 (P≤0.027) and DAS28(CRP) observed for all doses versus placebo at Week 2. Mean decreases in DAS28(CRP) from baseline increased over time with statistically significant improvements observed versus placebo at each time point for each dose.
Although the incidence of adverse events (AEs) was higher with ABT-494 than placebo, and there appeared to be a trend towards higher incidence at higher doses, AE incidence was similar across the groups, with most being mild and infections the most frequent.
Optimal doses in terms of risk-benefit will be evaluated in phase 3 studies to confirm the efficacy and safety of ABT-494 observed here.