Arthritis Rheumatol 2016;68:2867–77The summary and accompanying slide deck have been developed in conjunction with the Genovese et al. study (Study 1) which examined ABT-494 in MTX-IR patients in order to compare and contrast the data. In these two Phase 2b studies, ABT-494 (a novel selective JAK-1 inhibitor) was shown to be effective in patients with active RA who were non-responders to MTX or at least one TNF inhibitor.Patients with active RA who had an inadequate response to MTX (study 1) or were refractory to or intolerant of previous treatment with at least one TNF inhibitor (study 2) were randomised to placebo or ABT-494 3-, 6-, 12- or 18 mg twice daily for 12 weeks, while continuing stable MTX treatment. Study 1 included an additional dose of 24 mg once daily.The primary efficacy endpoint was the proportion of patients achieving at least an ACR20 response at Week 12. In MTX inadequate responders, this was achieved by 62%–80% of ABT-494-treated patients, compared with 46% for placebo (P<0.05 for 6-, 12- and 24 mg doses). The response rates in anti-TNF inadequate responders were between 53% and 71%, compared with 34% for placebo (all P<0.05).The incidence of AEs was similar across ABT-494 groups in study 1; most were mild, and infections were the most frequent. In study 2, infection rates were higher at higher doses of ABT-494, but no infections were serious.Selective JAK inhibition with ABT-494 was effective in patients with active RA refractory to treatment with MTX or TNF inhibitors. ABT-494 demonstrated a safety and tolerability profile consistent with other JAK inhibitors in RA.