medwireNews: Results of the SELECT-BEYOND trial suggest that the Janus kinase (JAK) inhibitor upadacitinib may be a useful treatment option for patients with treatment-refractory rheumatoid arthritis (RA).
Speaking to medwireNews, lead author Mark Genovese (Stanford University School of Medicine, Palo Alto, California, USA) said: “This phase III trial specifically focused on patients who had already had an inadequate response to biologics.”
He explained that participants with active RA who were undergoing stable treatment with conventional DMARDs but had experienced an inadequate response or intolerance to at least one biologic agent were randomly assigned to receive the selective JAK1 inhibitor at a dose of 15 mg or 30 mg once daily, or to receive placebo, for 12 weeks. After this time, patients in the placebo group were randomly allocated to one of the upadacitinib groups for an additional 12 weeks.
At the 12-week follow-up, a significantly higher proportion of patients receiving upadacitinib achieved at least a 20% improvement in ACR criteria (ACR20) compared with those given placebo, with rates of 65% for the 164 patients in the 15 mg group and 56% for the 165 patients in the 30 mg group versus 28% for the 169 participants receiving placebo.
Describing this as a “really tremendous response rate,” Genovese said that “we’ve never seen a trial that’s had [ACR20 response rates] in the 60s for this population.”
Furthermore, patients receiving upadacitinib 15 mg or 30 mg were significantly more likely to achieve low disease activity – defined as a Disease Activity Score at 28 joints based on C-reactive protein of 3.2 points or lower – than those in the placebo group, with 43% and 42% versus 14% of patients, respectively, meeting this coprimary endpoint.
“This is a phenomenal response in 12 weeks with a drug refractory population,” remarked Genovese.
The clinical improvements observed at week 12 were maintained at week 24, and patients who switched from placebo to upadacitinib at week 12 experienced a similar positive response.
Genovese explained that the safety findings were “fairly consistent with what you would expect to see” in the population studied.
In all, 55.5% of patients receiving upadacitinib 15 mg, 67.3% of patients receiving upadacitinib 30 mg, and 56.2% of those in the placebo group experienced adverse events (AEs) from baseline to week 12, and 2.4%, 9.1%, and 5.3% of patients, respectively, discontinued treatment due to AEs. The corresponding rates of serious adverse events were 4.9%, 7.3%, and 0.0%.
One patient in each of the upadacitinib groups experienced pulmonary embolism between baseline and week 12, and herpes zoster infection occurred in one patient in the 15 mg group, four patients (2.4%) in the 30 mg group, and one patient receiving placebo. Two deaths were reported in patients receiving upadacitinib during the study; one patient died due to cardiac failure between baseline and week 12, and one patient died from unknown causes between weeks 12 and 24.
Summing up the results, Genovese said the SELECT-BEYOND trial demonstrated that upadacitinib is a “very effective drug in a refractory patient population.”
The findings were presented in a late-breaking poster session at the 2017 ACR/ARHP Annual Meeting in San Diego, California, USA.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group
This information is brought to you by medwireNews and is not sponsored by, nor a part of, the American College of Rheumatology