Researchers Explore Safety Profile of Upadacitinib in Rheumatoid Arthritis Patients

Stanley Cohen, MD

Recent studies show upadacitinib, a Janus kinase inhibitor, has promise in treating rheumatoid arthritis.

A team, led by Stanley B. Cohen, MD, Metroplex Clinical Research Center, examined the safety profile of upadacitinib at 15 mg and 30 mg once daily for patients with moderately to severely active rheumatoid arthritis.

In the study, the investigators analyzed and summarized treatment-emergent adverse events and laboratory data from 5 randomized, placebo- or active-controlled phase 3 trials testing upadacitinib for patients with rheumatoid arthritis.

Exposure-adjusted event rates were shown for placebo (3 trials; 12/14 weeks), methotrexate (2 trials; mean exposure: 36 weeks), adalimumab (1 trial; mean exposure: 42 weeks), upadacitinib 15 mg (5 trials; mean exposure: 53 weeks), and upadacitinib 30 mg (4 trials; mean exposure: 59 weeks).

A total of 3834 patients received 1 or more doses of upadacitinib 15 mg (n = 2630) or 30 mg (n = 1204), for a total of 4020.1 patient-years of exposure. The most common reported treatment-emergent adverse events were upper respiratory tract infections, nasopharyngitis, and urinary tract infections.

The rates of serious infections were similar between upadacitinib 15 mg and adalimumab. However, these rates were higher when compared to methotrexate. The rates of herpes zoster and creatine phosphokinase (CPK) elevations were higher in both study drug groups when compared to methotrexate and adalimumab. In addition, the rates of gastrointestinal perforations were higher in the upadacitinib 30 mg group.

The rates of deaths, malignancies, adjudicated major adverse cardiovascular events (MACEs), and venous thromboembolic events (VTEs) were similar across all the treatment groups.

“In the phase III clinical program for [rheumatoid arthritis], patients receiving upadacitinib had an increased risk of herpes zoster and CPK elevation versus adalimumab,” the authors wrote. “Rates of malignancies, MACEs and VTEs were similar among patients receiving upadacitinib, methotrexate or adalimumab.”

Earlier this year, upadacitinib demonstrated superior improvement in signs and symptoms of rheumatoid arthritis when compared to abatacept based on a change in Disease Activity Score-28-joint count (DAS28)C-reactive protein (CRP).

A team of researchers based in Switzerland assessed the efficacy and safety of upadacitinib versus abatacept in patients with prior inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs. The team randomized patients to receive either once-daily upadacitinib 15 mg or intravenous abatacept (at day 1 and weeks 2, 4, 8, 12, 16, and 20). All patients continued background stable conventional synthetic DMARDs.

In total, 612 patients were treated and 67% had received 1 prior biologic DMARD, 22% received 2 prior biologic DMARDs, and 10% received >3 prior biologic DMARDs.

Clinical remission, ACR50, and ACR70 responses remained higher with upadacitinib versus abatacept through week 24 (nominal P <.05). However, incidence of serious treatment-emergent adverse events, adverse events leading to discontinuation, hepatic disorders, and Creatine Phosphokinase elevations were higher with upadacitinib versus abatacept.

Upadacitinib showed superior improvement in signs and symptoms versus abatacept. In addition, the study authors noted the safety profile of upadacitinib was consistent with the phase 3 rheumatoid arthritis studies and no new risks were identified.

The study, “Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme,” was published online in the Annals of the Rheumatic Diseases.