乌鸦传媒

Patients with rheumatoid arthritis (RA) treated with upadacitinib (Rinvoq) reported outcomes that were similar or superior to those seen with adalimumab (Humira), a post-hoc analysis of randomized clinical trial data found.

At week 12 of a phase III study known as SELECT-COMPARE, the least squares mean change from baseline on patient global assessment was -30.39 (95% CI -32.62 to -28.16) for patients given upadacitinib, according to the study by Vibeke Strand, MD, of Stanford University in California, and colleagues.

In contrast, changes from baseline were -23.55 (95% CI -26.43 to -20.67, P<0.05) for those receiving the standard of care active comparator adalimumab, and -15.24 (95% CI -17.44 to -13.04, P<0.05) for those assigned to placebo, the investigators reported in . (The analysis was sponsored by upadacitinib's manufacturer, AbbVie, and some authors were company employees.)

Patient-reported outcomes such as pain, fatigue, and morning stiffness that reflect health-related quality of life in RA have assumed greater significance in recent years, as these aspects of disease can have a significant impact on work productivity and social/leisure activities.

Upadacitinib is a Janus kinase (JAK) inhibitor with primary activity against JAK-1 that was approved for use in RA in 2019. enrolled 1,629 patients with moderate to severely active RA who had previously had an inadequate response to methotrexate, randomizing them to oral upadacitinib, 15 g once daily, subcutaneous adalimumab, 40 mg every other week, or placebo. All patients also received background methotrexate.

In the original study, at week 26 more patients in the upadacitinib group achieved remission or low disease activity than in the adalimumab or placebo groups.

Patients' mean age was 54, 79% were women, and disease duration averaged 8 years. Mean Disease Activity Scores in 28 joints were 5.8 to 5.9, indicating high disease activity.

Impairments in quality of life on measures such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and the Short Form (SF)-36 were considered substantial, the investigators reported.

At week 12, changes from baseline in the upadacitinib group differed significantly on all patient-reported outcomes compared with placebo, and were significantly greater than adalimumab for several:

• Pain, -31.76 (95% CI -33.96 to -29.56) vs -25.31 (95% CI -28.16 to -22.47)

• HAQ-DI, -0.61 (95% CI -0.66 to -0.56) vs -0.51 (95% CI -0.57 to -0.44)

• Morning stiffness severity, -3.37 (95% CI -3.59 to -3.15) vs -2.86 (95% CI -3.14 to -2.57)

• FACIT-F, 8.95 (95% CI 7.98 to 9.93) vs 7.44 (95% CI 6.25 to 8.64)

• SF-36 physical, 7.89 (95% CI 7.11 to 8.68) vs 6.27 (95% CI 5.31 to 7.23)

In addition, changes from baseline at week 12 in all eight individual domains of the SF-36 (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health) were greater when upadacitinib was compared with placebo and were significantly different from adalimumab in six domains (role-physical, bodily pain, general health, vitality, social functioning, physical functioning).

Compared with placebo, significantly more patients receiving upadacitinib achieved minimum clinically important differences on many outcomes at week 12, and more patients on upadacitinib achieved scores equal to or greater than normative values in HAQ-DI (21% vs 14%, P<0.05) and SF-36 physical (16% vs 11%, P<0.05).

Beginning at week 14, patients with less than 20% improvement in tender or swollen joints were switched from placebo to upadacitinib or adalimumab or from upadacitinib to adalimumab. At week 26, all patients on placebo were given upadacitinib.

At week 48, patients on upadacitinib had significantly greater changes from baseline compared with adalimumab on these outcomes:

• Patient global assessment, -35.71 (95% CI -38.37 to -33.05) vs -29.99 (95% CI -33.32 to -26.66)

• Pain, -36.75 (95% CI -39.42 to -34.08) vs -31.87 (95% CI -35.20 to -28.54)

• HAQ-DI, -0.69 (95% CI -0.76 to -0.63) vs -0.57 (95% CI -0.65 to -0.50)

• Morning stiffness severity, -3.87 (95% CI -4.14 to -3.61) vs -3.38 (95% CI -3.71 to -3.05)

• FACIT-F, 9.67 (95% CI 8.66 to 10.68) vs 8.24 (95% CI 6.98 to 9.50)

• SF-36 physical, 9.51 (95% CI 8.65 to 10.37) vs 7.84 (95% CI 6.77 to 8.92)

In addition, more patients receiving upadacitinib reported clinically meaningful improvements from week 12 to week 48 for patient global assessment, pain, HAQ-DI, FACIT-F, severity and duration of morning stiffness, and SF-36 physical and mental components.

"Overall, patient-reported outcomes with upadacitinib treatment met or exceeded treatment with adalimumab, especially in key domains of pain, function, and vitality/fatigue," the investigators wrote. "Upadacitinib may offer an effective treatment option for methotrexate-inadequate responsive patients with RA with better effects than a mainstay of current standard of care, adalimumab."

A limitation of the study, the researchers said, is that clinical trial participants have specific inclusion and exclusion criteria and thus may differ from the larger RA population overall.

Comment