Results from the phase 3 SELECT-BEYOND clinical trial evaluating Upadacitinib ( ABT-494 ), an investigational oral JAK1-selective inhibitor, in patients with moderate to severe rheumatoid arthritis who did not adequately respond or were intolerant to treatment with biologic DMARDs ( bDMARDs ) were announced.
Results showed that after 12 weeks of treatment, both once-daily doses of Upadacitinib ( 15 mg and 30 mg ) met the study's primary endpoints of ACR20 and low disease activity ( LDA ).
All ranked secondary endpoints were also achieved with both doses.
Rheumatoid arthritis is a chronic and debilitating disease that affects an estimated 23.7 million people worldwide.
Despite progress in the treatment of rheumatoid arthritis, many patients still do not achieve remission or low disease activity targets.
Results at week 12 showed that of patients receiving an oral once-daily dose of 15 mg or 30 mg Upadacitinib, ACR20/50/70 response was achieved in 65/34/12% of patients with the 15 mg dose, respectively, and 56/36/23% with the 30 mg dose, respectively, compared to 28/12/7% in the placebo group.
These results were statistically significant compared to placebo ( p less than 0.001 ) for all comparisons except ACR70 for the 15 mg dose.
Additionally, a significantly higher proportion of Upadacitinib patients in both doses achieved LDA and clinical remission targets at week 12 compared to patients receiving placebo ( p less than 0.001 ).
Low disease activity 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.
Results continued to be encouraging through week 24. Of patients treated with Upadacitinib from study entry, ACR20/50/70 response was achieved in 62/43/22% of patients with the 15 mg dose and 59/43/24% with the 30 mg dose at week 24.
Low disease activity was achieved by 52% of patients receiving either dose of Upadacitinib.
Clinical remission was achieved by 32% and 35% of patients in the 15 mg and 30 mg groups, respectively.
Comparisons to placebo cannot be made at week 24, since all placebo patients received either Upadacitinib 15 mg or 30 mg beginning at week 12.
In this study, the safety profile of Upadacitinib was consistent with previously reported phase 2 trials and the phase 3 SELECT-NEXT clinical trial.
No new safety signals were detected.
During the placebo-controlled period, serious adverse events occurred in 5/7/0% of patients in the 15 mg/30 mg/placebo groups, respectively.
There were two deaths reported during the study. One was a patient in the 15 mg dose group with cause of death 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 during hospitalization.
Inclusive of the case mentioned above, a total of two cases of pulmonary embolism and no deep vein thrombosis were reported during the placebo-controlled period. ( Xagena )
Source: Abbvie, 2017