AbbVie announced positive top-line results from the phase 3 SELECT-COMPARE clinical trial where after 12 weeks, 15 mg, once daily, upadacitinib (formerly ABT-494) met primary endpoints of ACR20 and clinical remission versus placebo in treatment of those with moderate to severe rheumatoid arthritis who are on a stable background of methotrexate and had an inadequate response.
All ranked secondary endpoints were also achieved versus placebo or adalimumab (40 mg every other week).
The study showed that at week 12, 71% of patients receiving an oral once-daily dose of 15 mg upadacitinib achieved an ACR20 response versus 36% of patients receiving placebo.
“These results show a significant impact on both signs and symptoms and radiographic progression compared to placebo, as well as improvements in important measures such as ACR response and low disease activity compared to adalimumab,” Michael Severino, MD, executive vice president, research and development and chief scientific officer, AbbVie, said in a statement. “We are excited by these strong results which add to the body of evidence that support the potential of upadacitinib to be an important treatment option for patients with rheumatoid arthritis.”
A greater proportion of patients receiving upadacitinib achieved clinical remission (based on Disease Activity 28 [DAS28] C-Reactive Protein [CRP]) versus those receiving placebo at week 12 (29% versus 6%, respectively).
Additionally, patients achieved ACR50/70 responses of 45%/25%, versus 15%/5% receiving placebo at week 12. Low disease activity based on DAS28 (CRP) was seen in 45% of patients receiving upadacitinib versus 29% receiving adalimumab and 14% receiving placebo at week 12, respectively.
Findings also demonstrated superiority of upadacitinib over adalimumab on ranked secondary endpoints. At week 12, 45% of upadacitinib patients achieved ACR50 versus 29% of patients receiving adalimumab. Upadacitinib was also superior to adalimumab in pain reduction, measured by the Patient’s Assessment of Pain, and improvements in physical function, measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 12.
Following 26 weeks of treatment, upadacitinib (n= 593) significantly inhibited radiographic progression measured by the change in modified total Sharp score (mTSS) from baseline, versus placebo (n= 599) (.24 versus .92, p<0.001). Inhibition of joint damage is important for rheumatoid arthritis patients because this can lead to permanent loss of function and subsequent disability.
The safety profile was consistent with previously reported results, and no new safety signals were detected.
Through week 26, serious adverse effects occurred while on the original randomized treatment assignment in 3.7% of patients receiving upadacitinib, 4.3% of patients receiving adalimumab and 2.9% of patients on placebo.
Researchers noted that serious infections occurred in 1.8%/1.5%/0.8% of patients on upadacitinib/adalimumab/placebo groups, respectively. There were no deaths in the upadacitinib group, 2 deaths in the adalimumab group and 2 deaths in the placebo group.
Additionally, there were no adjudicated major adverse cardiovascular events (MACE) reported in the upadacitinib group through week 26, however, there were 2 patients with MACE in the adalimumab group and 3 in the placebo group.
In terms of adjudicated venous thromboembolic events (VTE) through week 26, 1 patient had a deep vein thrombosis (DVT) and another with a pulmonary embolism (PE) in the upadacitinib group, 3 patients with PE in the adalimumab group and 1 with PE in the placebo group.
The rate of DVT and PE remains consistent with the background rate for the patient population.
The SELECT-COMPARE phase 3 trial is designed to evaluate the safety and efficacy of upadacitinib versus placebo and adalimumab in adult patients with moderate to severe rheumatoid arthritis. In the trial, patients received background methotrexate and were randomized 2:2:1 to receive 15 mg once-daily upadacitinib, placebo or 40 mg adalimumab (given via subcutaneous injection every other week).
Primary endpoints included the percentage of subjects achieving ACR20 and clinical remission, based on DAS 28 (CRP) after 12 weeks of treatment, while secondary endpoints included change in the mTSS versus placebo, a comparison versus adalimumab in percentage of subjects achieving ACR50, low disease activity, changes in pain as measured by the Patient’s Assessment of Pain (based on VAS) and changes in physical function measured by the HAQ-DI.
SELECT-COMPARE, an ongoing study, consists of a 48-week randomized, double-blind treatment period, followed by a long-term extension study of up to 5 years. The trial is part of the larger, more robust SELECT phase 3 program that evaluates the assessments of efficacy, safety and tolerability across more than 4000 patients with moderate to severe rheumatoid arthritis in 6 studies.
Upadacitinib is currently being tested in phase 3 trials of in rheumatoid arthritis, psoriatic arthritis and Crohn’s disease, and is being investigated to treat ulcerative colitis, ankylosing spondylitis, atopic dermatitis and giant cell arteritis.
Currently, upadacitinib is not approved by regulatory authorities and the drug’s safety and efficacy have not been established.
APRIL 09, 2018