Treatment with the recently approved oral selective JAK-1 inhibitor upadacitinib (Rinvoq) resulted in significant benefits in various patient-reported outcomes among individuals with refractory rheumatoid arthritis (RA), analysis of data from a phase III trial found.
For instance, change on the patient global assessment of disease activity at week 12 was -26.04 (95% CI -30.16 to -21.93) among patients receiving upadacitinib, 15 mg per day, and -29.27 (95% CI -33.43 to -25.12) for those given 30 mg per day compared with -10.03 (-14.22 to -5.84) for those receiving placebo (P≤0.001 vs placebo for both), according to Vibeke Strand, MD, of Stanford University in California, and colleagues.
And on the Health Assessment Questionnaire Disability Index (HAQ-DI), the changes at week 12 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), respectively, compared with -0.16 (95% CI -0.25 to -0.08) in the placebo group (P≤0.001 for both), the researchers reported online in .
Aside from the objective findings such as swollen joints, radiographic changes, and diminished life expectancy, patients with RA commonly report numerous subjective disease manifestations that can have a negative influence on their quality of life and functioning, including pain, fatigue, stiffness, and sleep disturbances. "Thus, understanding the patient's perspective of how a therapy impacts multiple aspects of health-related quality of life is crucial when evaluating the efficacy of treatments for RA," the investigators observed.
was a phase III trial comparing upadacitinib in dosages of 15 or 30 mg per day versus placebo among patients who had not responded to biologic disease-modifying antirheumatic drugs (DMARDs). have shown that treatment with the JAK inhibitor at those two doses resulted in higher rates of 20% improvement on the criteria of the American College of Rheumatology at week 12 (65% and 56% vs 28%, P<0.0001 for both). Significantly more patients in the two upadacitinib groups also achieved low disease activity, defined as a Disease Activity Score in 28 joints below 3.2 (43% and 42% vs 14%, P<0.0001 for both).
To explore whether the improvements seen on those conventional disease assessment measures were accompanied by benefits on patient-reported outcomes, Strand and colleagues analyzed the results on various measures of pain, health-related quality of life, morning stiffness, and insomnia severity.
Mean age for the patients was 57, the majority were women, and mean RA disease duration was 13 years. Previous treatment with one or more tumor necrosis factor inhibitors had failed for almost 90% of patients, most often for lack of efficacy. During the trial, patients also were on conventional DMARDs.
On a visual analog scale of pain, the 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), respectively, compared with -10.38 (95% CI -14.60 to -6.16) for placebo (P≤0.001 for both).
The Short Form 36 (SF-36) Health Survey rates health-related quality of life over eight domains. At baseline, mean SF-36 scores averaged 25 to 50 points lower than in the general population, which represented "substantial impairments," the authors noted. At week 12, the physical component summary score of the SF-36 showed 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), respectively, compared with 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 two upadacitinib groups versus -15.07 (95% CI -43.30 to 13.16) for the placebo group (P≤0.001 for both). On the Insomnia Severity Index, only the 30 mg group had a significantly greater change compared with placebo (-3.32, 95% CI -4.15 to -2.49 vs -1.69, 95% CI -2.55 to -0.83, P<0.01).
The median time to response on both the pain visual analog scale and the HAQ-DI was 2 weeks for the upadacitinib groups compared with 4 weeks in the placebo group.
"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," Strand and colleagues concluded.
A limitation of the study was its short duration, and further studies will be needed to determine whether the benefits of upadacitinib persist long term, the team noted.
Disclosures
The study was funded by AbbVie.
The authors reported financial relationships with AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Eli Lilly, Novartis, Pfizer, Regeneron, Sanofi, UCB, Merck, Celltrion, Roche, and Sandoz; several were employees of AbbVie.
Primary Source
Arthritis Research & Therapy
Strand V, 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 Res Ther 2019; doi:10.1186/s13075-019-2059-8.