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Treatment with the recently approved oral, selective JAK-1 inhibitor upadacitinib (Rinvoq, AbbVie) resulted in significant improvements in various patient-reported outcomes among individuals with rheumatoid arthritis who have had inadequate responses to biologic DMARDs, researchers report in Arthritis Research & Therapy.
Treatment with the recently approved oral, selective JAK-1 inhibitor upadacitinib (Rinvoq, AbbVie) resulted in significant improvements in various patient-reported outcomes among individuals with rheumatoid arthritis who have had inadequate responses to biologic disease-modifying antirheumatic drugs (DMARDs), say researchers recently writing in Arthritis Research & Therapy.
Rheumatoid arthritis is associated with substantial clinical burden and shortened life expectancy. Many patients with rheumatoid arthritis experience impaired physical functioning, chronic pain, fatigue, stiffness, and sleep disturbances, resulting in a reduced health-related quality of life (HRQOL).
Despite several treatment options, a significant proportion of patients with rheumatoid arthritis become refractory to available therapies. Janus kinase (JAK) inhibitors are a new class of targeted synthetic DMARDs approved for use in rheumatoid arthritis. Upadacitinib, a potent JAK inhibitor with preferential activity against JAK1, has been evaluated across rheumatoid arthritis populations, including inadequate responders to conventional-synthetic DMARDs and biologic DMARDs.
“Not only is it essential to demonstrate that new treatments reduce the signs and symptoms of active RA in patients with refractory disease, but it is also necessary to show that these new treatments improve HRQOL outcomes from the patient’s perspective,” wrote the authors of the study, led by Namita Tundia, Ph.D., of AbbVie in Chicago.
In this phase 3 study, called SELECT-BEYOND, researchers compared upadacitinib in dosages of 15 or 30 mg per day versus placebo among 498 patients who had not responded to biologic DMARDs and were receiving background conventional-synthetic DMARDs. While the trial has previously shown that more upadacitinib-treated patients had ACR20 responses and lower disease activity than placebo, this latest analysis assessed clinically meaningful improvements in patient-reported outcomes at 12 weeks. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning stiffness, and Insomnia Severity Index (ISI).
Change on PtGA at week 12 was -26.04 (95% CI -30.16 to -21.93) among patients prescribed upadacitinib, 15 mg per day, and -29.27 (95% CI -33.43 to -25.12) for those receiving 30 mg per day, versus -10.03 (95% CI -14.22 to -5.84) for those receiving placebo (P≤0.001 vs placebo for both). On the HAQ-DI, the respective changes for the 15 mg and 30 mg groups were -0.41 (95% CI -0.50 to -0.33) and -0.44 (95% CI -0.52 to -0.35), versus -0.16 (95% CI -0.25 to -0.08) in the placebo group (P≤0.001 for both).
On a visual analog scale of pain, the respective changes from baseline in the 15 mg and 30 mg groups at week 12 were -25.91 (95% -30.05 to -21.76) and -30.92 (95% CI -35.12 to -26.72), versus -10.38 (95% CI -14.60 to -6.16) for placebo (P≤0.001 for both). The physical component summary score of the SF-36 showed respective changes from baseline in the 15 mg and 30 mg groups of 5.83 (95% CI 4.60 to 7.05) and 7.02 (95% CI 5.78 to 8.25) versus 2.39 (95% CI 1.14 to 3.64) for placebo (P≤0.001 for both).
Changes in the duration of morning stiffness were -81.47 minutes (95% CI -109.52 to -53.42) and -79.13 minutes (95% CI -107.26 to -51) for the 15 mg and 30 mg groups, respectively, versus -15.07 (95% CI -43.30 to 13.16) for the placebo group (P≤0.001 for both). On the ISI, only the 30 mg group had a significantly greater change versus placebo (-3.32, 95% CI -4.15 to -2.49 vs -1.69, 95% CI -2.55 to -0.83, P<0.01).
"Upadacitinib treatment resulted in rapid and clinically meaningful improvements in outcomes of importance to patients with refractory disease: disease activity, pain, physical function, and morning stiffness, even in a difficult-to-treat population," the authors wrote.
Due to the short duration of the study, the authors recommended further research is needed to determine whether the benefits of upadacitinib persist in the long term.
Vibeke Strand, Michael Schiff, Namita Tundia, et al. “Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs.”Arthritis Research and Therapy. December 2, 2019. doi:10.1186/s13075-019-2059-8