Upadacitinib matches, exceeds adalimumab for improving patient-reported outcomes in RA
Upadacitinib is equivalent or superior to adalimumab in improving patient-reported outcomes among those with rheumatoid arthritis and an inadequate response to methotrexate, according to data published in Rheumatology.
“Despite major progress in the treatment of RA, there still remains a large unmet need, as a minority of patients with RA achieve or maintain remission or low disease activity (LDA) with stringent metrics,” Vibeke Strand, MD, MACR, FACP, of Stanford University, and colleagues wrote. “Novel therapies as well as different ways to utilize existing therapies are therefore needed to complement available interventions to address the unmet need.”
“Upadacitinib (UPA) is a potent JAK inhibitor with preferential activity towards JAK-1, recently approved for the treatment of RA,” they added. “UPA has also shown efficacy as combination therapy and monotherapy in [patients with an inadequate response to methotrexate (MTX-IR)]. Improvements in [patient-reported outcomes (PROs)] with UPA were reported in conventional synthetic DMARD-IR and biologic DMARD-IR populations in the phase 3 program; however, the effect of UPA on PROs in comparison with widely used therapies such as [adalimumab (ADA)] is not well known.”
To analyze the effect of upadacitinib (Rinvoq, AbbVie), compared with placebo and adalimumab (Humira, AbbVie), on patient-reported outcomes among patients with RA and an inadequate response to methotrexate, Strand and colleagues studied data from SELECT-COMPARE. According to the researchers, SELECT-COMPARE is a phase 3, double-blind, parallel-group, placebo-controlled, active-comparator trial of adults with moderate to severely active RA and an inadequate response to methotrexate.
Participants were assigned to one of three groups, with 651 receiving 15 mg of upadacitinib once daily, another 651 receiving a matching placebo and 327 patients treated with 40 mg of adalimumab every other week. In addition, all participants received a stable background of methotrexate therapy. Later, at weeks 14, 18 and 22, participants with less than 20% improvement in tender or swollen joints were switched from placebo or adalimumab to upadacitinib, or from upadacitinib to adalimumab.
At week 26, all patients in the placebo group were transferred to upadacitinib, and any participants who had not achieved low disease activity were switched from upadacitinib to adalimumab or adalimumab to upadacitinib, if not rescued earlier in the study.
Patient-reported outcomes were assessed in all participants over 48 weeks. These outcomes included Patient Global Assessment of Disease Activity (PtGA), visual analogue scale (VAS), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the 36-Item Short Form Survey (SF-36), morning stiffness duration and severity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and work stability. The researchers evaluated least squares mean changes, as well as the proportions of participants reporting improvements that were greater than or equal to minimal clinically important differences and scores greater than or equal to normative values.
According to the researchers, upadacitinib and adalimumab resulted in greater least square mean changes from baseline, compared with placebo, across all patient reported outcomes (P < .05) at week 12, as well as pain and morning stiffness severity (P < .05) at week 2. In addition, upadacitinib was superior to placebo (P < .05), and similar to adalimumab, in reported improvements greater than or equal to minimal clinically important differences across all outcomes at week 12.
Meanwhile, upadacitinib resulted in greater least square mean changes from baseline in PtGA, pain, HAQ-DI, morning stiffness severity, FACIT-F and the SF-36 physical component summary, compared with adalimumab, (all P < .05) at week 12. More patients who received upadacitinib, compared with adalimumab, reported scores greater than or equal to normative values in HAQ-DI and SF-36 physical component summary (P < .05) at week 12. In addition, more participants in the upadacitinib group, compared with the adalimumab group, maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and morning stiffness through 48weeks.
“Upadacitinib and adalimumab resulted in greater least square mean changes from baseline, compared with placebo, across all patient reported outcomes at week 12, and pain and morning stiffness at week 2,” Strand told Healio Rheumatology. “These improvements with upadacitinib were greater than adalimumab in PtGA, pain, HAQ, morning stiffness severity, FACIT-F, SF-36 physical component summary and six out of eight domains. The improvements were clinically meaningful and similarly reported between upadacitinib and adalimumab.
“More upadacitinib than adalimumab patients reported scores greater than or equal to normative values — eg, as if they didn’t have arthritis — in HAQ-DI and SF-36 physical component summary at week 12,” she added. “Also, more upadacitinib treated patients than adalimumab continued to report clinically meaningful improvements in PtGA, pain, HAQ, FACIT and morning stiffness to 48 weeks. This is important as reflects clinical efficacy of UPA at approved dose of 15 mg once daily.”