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The results highlight a significant improvement in rheumatoid arthritis signs and symptoms for those who used upadacitinib over placebo and adalimumab.
Roy Fleischmann, MD
New research suggests combination therapy with upadacitinib plus methotrexate maintains significantly higher levels of clinical response in patients with rheumatoid arthritis compared to adalimumab and methotrexate through 72 weeks.
The findings were presented at the European E-Congress of Rheumatology 2020 (EULAR 2020) due to the cancellation of the live EULAR 2020 annual meeting. The results highlighted a significant improvement in rheumatoid arthritis signs and symptoms for those who used upadacitinib over placebo and adalimumab.
Roy Fleischmann, MD, and a team of investigators reported the safety and efficacy of upadacitinib versus adalimumab up to 72 weeks in patients with rheumatoid arthritis from the ongoing long-term extension of the SELECT-COMPARE study. The SELECT-COMPARE study contained patients with inadequate response to methotrexate. The team aimed to learn if upadacitinib, a Janus Kinase (JAK) 1-selective inhibitor, could help such patients.
Patients were randomized to either receive once-daily upadacitinib (15 mg), placebo, or adalimumab (40 mg) every other week. All patients continued background methotrexate. For the first 48 weeks, the study was double-blind.
A patient was rescued from placebo to upadacitinib, upadacitinib to adalimumab, or adalimumab to upadacitinib if there was <20% improvement in their tender and swollen joint count at weeks 14, 18, and 22. Patients were also rescued between weeks 14-26 if their Clinical Disease Activity Index was >10 at week 26.
Placebo patients who were not rescued were switched to upadacitinib at week 26. Patients then continued their upadacitinib or adalimumab in a blinded manner until the final patient had their week 48 visit. After that, patients received open-label treatment. Each patient then had a study visit at week 60, 72, and every 12 weeks after.
Overall, Fleischmann and the team included more than 1500 patients—651 were randomized at baseline to receive upadacitinib, while 651 received placebo and 327 patients were randomized to adalimumab. Following initial randomization, 252 patients were switched from upadacitinib to adalimumab, 159 went from adalimumab to upadacitinib, and all placebo patients were switched to receive upadacitinib.
At week 48, 1403 patients entered long-term extension of the study. There were 1091 patients in the upadacitinib group—565 switched from placebo, 66 rescued from adalimumab, and 460 on continued upadacitinib. There were 312 patients on adalimumab—110 rescued from upadacitinib and 202 on continued adalimumab. Cumulative exposures were 1396.7 and 515.1 patient-years for upadacitinib and adalimumab.
Upadacitinib plus methotrexate was well-tolerated based on the frequency of adverse events, including serious adverse events, adverse events leading to discontinuation of the study drug, and adverse events of special interest, which included serious infections, malignancy, adjudicated major adverse cardiac events, or venous thrombosis. Rates of events including those of special interest were comparable between upadacitinib plus methotrexate and adalimumab plus methotrexate. Herpes zoster, lymphopenia, hepatic disorder, and CPK elevation were higher with upadacitinib plus methotrexate.
Significantly greater proportions of those who received upadacitinib plus methotrexate achieved ACR20/50/70 (P <.01/.001/.001) at weeks 60 and 72, along with low disease activity (P <.001) and remission (P <.001) compared to patients who received adalimumab plus methotrexate. There were significantly better improvements in pain and function in the upadacitinib group compared to adalimumab.
The study, “Long-Term Safety and Effectiveness of Upadacitinib or Adalimumab in Patients With Rheumatoid Arthritis: Results at 72 Weeks From the Select-Compare Study,” was published on the EULAR 2020 website.