New phase 3 data from the SELECT-CHOICE clinical trial have shown that Upadacitinib ( Rinvoq ), 15 mg, once daily, met the primary endpoint of non-inferiority versus Abatacept ( Orencia ) on change from baseline in Disease Activity Score 28 C-Reactive Protein ( DAS28-CRP ) at week 12.
In addition, Upadacitinib met the key secondary endpoints of superiority versus Abatacept on change from baseline in DAS28-CRP at week 12 and proportion of patients achieving clinical remission at week 12 as measured by DAS28-CRP less than 2.6.
The study evaluated Upadacitinib in adult patients with moderate to severe active rheumatoid arthritis and prior inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs ( DMARDs ).
SELECT-CHOICE is the sixth and final phase 3 study from the SELECT rheumatoid arthritis clinical trial program.
Upadacitinib is a selective and reversible JAK inhibitor, approved for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more DMARDs.
Despite tremendous progress in the treatment of rheumatoid arthritis, about 70% of patients are still not achieving clinical remission with established therapies.
SELECT-CHOICE represents the first head-to-head study in rheumatoid arthritis patients who have failed biologic DMARDs and has compared Upadacitinib to a different biologic DMARD.
In this study, Upadacitinib met both the primary ( non-inferiority ) and secondary ( superiority ) endpoints, with a change from baseline in DAS28-CRP at week 12 of -2.52 compared to -2.00 in patients treated with Abatacept.
In addition, 30% of patients receiving Upadacitinib has achieved clinical remission at week 12 ( DAS28-CRP less than 2.6 ) compared to 13% of patients receiving Abatacept ( p less than 0.001 ).
ACR20/50/70 responses were also higher in the Upadacitinib group compared to the Abatacept group ( 76/46/22% versus 66/34/14%, respectively, nominal p less than 0.05 ) at week 12.
Improvements in disease activity and remission rates were maintained through 24 weeks.
The safety profile of Upadacitinib ( 15 mg ) was consistent with that observed in previously reported studies in rheumatoid arthritis, with no new safety risks detected.
Through week 24, serious adverse events occurred in 3.3% of patients in the Upadacitinib group, compared to 1.6% of patients in the Abatacept group.
There were three cases of serious infection reported in the Upadacitinib group and one in the Abatacept group.
There were also 23 cases of hepatic disorder ( primarily liver enzyme elevations ) in the Upadacitinib group compared to five cases of hepatic disorder in the Abatacept group.
All hepatic disorder events were non-serious.
Most of the events were transient ALT/AST elevations and considered mild to moderate in severity. None led to study drug discontinuation.
Four cases of herpes zoster were reported in the Upadacitinib group and four cases in the Abatacept group.
Across both groups, there were no malignancies reported.
One major adverse cardiovascular event ( MACE ) and two adjudicated cases of venous thromboembolic events ( VTE ) were reported in the Upadacitinib group, and both patients had at least one risk factor for VTE. There were no MACE and thromboembolic event reported in the Abatacept group.
There were two deaths in the Upadacitinib group, one of which was non-treatment emergent, as well as one non-treatment emergent death in the Abatacept group. ( Xagena )
Source: Abbvie, 2020