Support for switching between upadacitinib and adalimumab in RA patients
medwireNews: 48-week results from the SELECT-COMPARE study indicate that upadacitinib has sustained efficacy in patients with rheumatoid arthritis (RA), and that individuals with an inadequate response to upadacitinib or adalimumab may benefit from switching to the alternate therapy.
The primary results of SELECT-COMPARE demonstrated that upadacitinib “was superior to placebo or adalimumab on background methotrexate for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks,” explain Roy Fleischmann (University of Texas Southwestern, Dallas, USA) and co-investigators.
They note that while clinical trials of Janus kinase (JAK) inhibitors “have demonstrated robust outcomes” among participants switching from a tumor necrosis factor (TNF) inhibitor to a JAK inhibitor due to inadequate response, there are “a lack of data on the outcomes of patients who are switched from a JAK inhibitor to a TNF inhibitor for the same reasons,” and “SELECT-COMPARE was uniquely designed” to evaluate this scenario.
In SELECT-COMPARE, patients with active RA despite methotrexate treatment were randomly assigned to receive upadacitinib 15 mg/day, adalimumab 40 mg every 2 weeks, or placebo, all given alongside methotrexate.
Participants with an inadequate response to adalimumab or placebo in the first 26 weeks were switched to upadacitinib, while those with an inadequate response to upadacitinib were switched to adalimumab. An inadequate response was defined as less than 20% improvement in tender or swollen joint counts at week 14, 18, or 22, or CDAI of more than 10 points at week 26, and all patients remaining on placebo at week 26 were switched to upadacitinib.
As reported in the Annals of the Rheumatic Diseases, ACR 20, 50, and 70 response rates at week 48 were significantly higher among the 651 patients originally assigned to upadacitinib compared with the 327 given adalimumab, at 65% versus 54%, 49% versus 40%, and 36% versus 23%, respectively.
In all, 48.6% of participants treated with adalimumab switched to upadacitinib, while 38.6% switched from the JAK inhibitor to the TNF inhibitor.
Fleischmann and team report that for many patients, responses “were rapid and continued to improve” after the switch, “with a consistently higher magnitude for those switched to upadacitinib from adalimumab versus those switched to adalimumab from upadacitinib.”
For example, at 6 months after switching, remission according to a CDAI score of 2.8 points or lower was achieved by 15% of patients switched to upadacitinib and 5% of those switched to adalimumab, while remission according to a DAS28-CRP score of less than 2.6 points was achieved by 35% and 21%, respectively.
The researchers note, however, that “this study was not powered to assess which switch strategy is more efficacious,” and “further appropriately powered studies, including other [biologic and targeted synthetic DMARDs], are needed to answer this important clinical question.”
They say that rates of treatment-emergent adverse events “appeared comparable between upadacitinib and adalimumab” in the SELECT-COMPARE study, with the exception of higher herpes zoster risk among upadacitinib-treated patients, at rates of 3.1 versus 1.3 per 100 patient–years.
“No new safety findings were observed with longer-term exposure to upadacitinib or in the period following the switch from adalimumab to upadacitinib,” they add.
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