Upadacitinib superior to methotrexate in treating rheumatoid arthritis
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Upadacitinib monotherapy, at 15 or 30 mg daily, significantly improves clinical, radiographic and patient-reported outcomes in rheumatoid arthritis, compared with weekly methotrexate, according to data published in Arthritis & Rheumatology.
“The Janus kinase (JAK) enzymes (JAK1, JAK2, JAK3, and TYK2) are important mediators of multiple cytokine-signaling pathways for normal cellular processes as well as for immune mediated inflammation,” Ronald van Vollenhoven, MD, of Amsterdam University Medical Centers, in the Netherlands, and colleagues wrote. “Orally administered JAK inhibitors (tsDMARDs) are approved for their established efficacy as monotherapy and combination therapy (with csDMARDs), versus bDMARDs across diverse RA patient populations.”
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“Upadacitinib, a potent, reversible JAK inhibitor, met all primary and ranked secondary endpoints in each of the pivotal Phase III trials, both as monotherapy and in combination with csDMARDs, across the spectrum of methotrexate-experienced patients with established RA via the SELECT clinical development program: NEXT, BEYOND, MONOTHERAPY and COMPARE,” they added.
To analyze the effect of upadacitinib (Rinvoq, AbbVie) monotherapy among patients with RA who have had little or no exposure to methotrexate, van Vollenhoven and colleagues conducted the SELECT-EARLY trial. A total of 947 patients, recruited from 236 sites across 43 countries, were randomized into one of three groups, with 315 participants receiving weekly methotrexate, 317 receiving 15mg of upadacitinib daily and 315 treated with 30 mg of upadacitinib daily. Treatments continued for 24 weeks.
The primary endpoints were the proportions of patients achieving 50% or greater response in the American College of Rheumatology (ACR) criteria at week 12, as well as the proportion of participants demonstrating a 28joint Disease Activity Score, including Creactive protein (DAS28-CRP), of less than 2.6 at week 24. A total of 840 participants completed 24 weeks of treatment.
According to the researchers, both upadacitinib dosages met their primary endpoints, with 52% of participants in the 15 mg group, as well as 56% of those in the 30 mg group, achieving ACR50 at week 12, compared with 28% of those treated with methotrexate (P < .001). In addition, 48% of patients in the 15 mg group, along with 50% in the 30 mg group, demonstrated a DAS28-CRP of less than 2.6, compared with 19% of those who received methotrexate (P < .001).
In addition, participants treated with upadacitinib, regardless of dose, reported statistically significant and clinically meaningful improvements in multiple outcomes, compared with methotrexate. Overall, 88% of those treated with 15 mg, and 89% of those in the 30 mg group demonstrated no radiographic progression. The frequency of treatment-emergent adverse events, through 24 weeks, was 65% for methotrexate, 64% for 15 mg of upadacitinib and 71% for 30 mg of upadacitinib. A total of six deaths were reported, including two in the 15 mg arm, three in the 30 mg arm and one in the methotrexate group.
“Overall, the study showed that upadacitinib was more effective than methotrexate and had a good benefit-risk profile,” van Vollenhoven told Healio Rheumatology. “Note that the FDA approval, and the [European Medicines Agency] approval, for upadacitinib is for patients who have already tried methotrexate where the methotrexate did not work sufficiently well, so what was done in this trial is currently off-label. Moreover, I think it is not likely that any new drug will be used as first-line treatment from the start, and methotrexate is still recommended by all major rheumatology organizations as the first treatment for RA.”
“I do expect that with time there will be changes in the way we practice, so that we will one day be able to choose the first-line therapy individually for each patient by matching their individual disease profile with the best treatment for them,” he added. “I think this was very much a forward-looking study that suggest a possible future for patient-centered and individualized therapy approaches, which could be applied both in RA but also in other autoimmune diseases.”
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