Two out of three rheumatoid arthritis patients treated once daily for 12 weeks with 15 mg of oral upadacitinib met the American College of Rheumatology’s criteria for a 20% improvement (ACR20), according to top-line results from the phase 3 SELECT-BEYOND trial. Patients receiving an oral once-daily dose of 30 mg achieved an ACR20 of 56%, AbbVie announced, compared with 28% ACR20 for a placebo group.
AbbVie said that two patients died in the trial but the deaths were not linked to the drug.
SELECT-BEYOND evaluated upadacitinib (ABT-494), an investigational JAK1-selective inhibitor, in patients with moderate-to-severe rheumatoid arthritis (RA) who did not adequately respond or were intolerant to treatment with biologic disease-modifying antirheumatic drugs. The 12-week results met the study's primary endpoints of ACR20 and low disease activity (LDA).
At week 12 in patients receiving oral once-daily upadacitinib, an ACR20, ACR50, and ACR70 response was achieved in 65%, 34%, and 12% of patients with the 15 mg dose, respectively, and 56%, 36%, and 23% with the 30 mg dose, respectively, compared to 28% 12%, and 7% in the placebo group. LDA was achieved by 43% and 42% of patients in the 15 mg and 30 mg groups, respectively, compared to 14% of patients receiving placebo. Clinical remission was achieved by 29% and 24% of patients in the 15 mg and 30 mg groups, respectively, compared to 10% of patients receiving placebo. All results were statistically significant compared to placebo (P
Results continued to be encouraging through week 24. Of patients treated with upadacitinib from study entry, ACR20, ACR50, and ACR70 responses were achieved in 62%, 43%, and 22% of patients with the 15 mg dose and 59%, 43%, and 24% with the 30 mg dose. LDA was achieved by 52% of patients receiving either dose of upadacitinib.
ACR20, ACR50, and ACR70 are defined as 20%, 50%, and 70% improvements in tender and swollen joint counts, patient assessments of pain, global disease activity and physical function, physician global assessment of disease activity, and acute phase reactant.
AbbVie said the safety profile of upadacitinib was consistent with previously reported trials, with no new safety signals. During the placebo-controlled period, serious adverse events occurred in 5%, 7%, and 0% of patients in the 15 mg, 30 mg, and placebo groups, respectively.
There were two deaths reported during the study. One was a patient in the 15 mg dose group whose cause of death was unknown. The second was a patient in the 30 mg dose group who presented with fever and diarrhea, subsequent heart failure, and presumed pulmonary embolism (PE) during hospitalization.
“At the time of initial report, both events were considered by the investigator as having no reasonable possibility of being related to the study drug,” AbbVie spokeswoman Jillian Griffin told Reuters.
Including the case described above, two cases of PE and no deep vein thrombosis (DVT) were reported during the placebo-controlled period. In the previously reported phase 3 SELECT-NEXT trial, no cases of DVT or PE occurred. Across the SELECT RA program, including both the placebo-controlled and extension periods, the rate of DVT and PE remains consistent with the background rate for the RA patient population.
Reuters noted that in April 2017, the FDA declined to approve Eli Lilly’s rival JAK inhibitor, baricitinib, calling for an additional clinical study. Three months later, Lilly said the FDA was concerned about a small but increased number of potentially dangerous blood clots seen in baricitinib patients in clinical trials.