Upadacitinib bests abatacept for efficacy in RA, with greater adverse event risk
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Upadacitinib is superior to abatacept in achieving remission and DAS28-CRP change, but is associated with more serious adverse events, among patients with rheumatoid arthritis refractory to biologic disease modifying antirheumatic drugs, according to data.
“Studies have shown remission with the use of upadacitinib in approximately 30% of patients regardless of previous treatment, including those who had not previously received methotrexate or who had had treatment failure with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs,” Andrea Rubbert-Roth, MD, of the Cantonal Clinic St. Gallen, in Switzerland, and colleagues wrote in the New England Journal of Medicine.
“Abatacept, a drug approved for the treatment of rheumatoid arthritis, modulates T-cell co-stimulation by binding to CD80 and CD86 receptors on antigen-presenting cells, thereby inhibiting T-cell proliferation and B-cell stimulation,” they added. “The efficacy and safety of abatacept have been shown in phase 3 trials involving patients with active rheumatoid arthritis and an inadequate response to methotrexate or biologic DMARDs.”
To compare the efficacy and safety of upadacitinib (Rinvoq, AbbVie) with abatacept (Orencia, Bristol-Myers Squibb) among patients with RA and an inadequate response to biologic DMARDs, Rubbert-Roth and colleagues conducted the 24-week, phase 3, double-blind SELECT-CHOICE trial. Participants were randomly assigned to receive either 15 mg of oral upadacitinib each day or intravenous abatacept, each in combination with conventional synthetic DMARDs. In all, 303 were treated with upadacitinib, while 309 were assigned to the abatacept group.
The primary endpoint was the change from baseline to week 12 in the composite Disease Activity Score for 28 joints, based on C-reactive protein level (DAS28-CRP), assessed for noninferiority. Secondary endpoints at week 12 included the superiority of upadacitinib over abatacept regarding in the DAS28-CRP change from baseline, and the percentage of patients achieving clinical remission, defined as a DAS28-CRP of less than 2.6.
According to the researchers, the changes in DAS28-CRP from baseline to 12 weeks was –2.52 for upadacitinib and –2 for abatacept (P < .001). Meanwhile, the proportion of patients who achieved complete remission was 30% for upadacitinib, compared with 13.3% for abatacept (P < .001). However, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group during the treatment period. In addition, more patients in the upadacitinib group demonstrated elevated hepatic aminotransferase levels, compared with those treated with abatacept.
“SELECT-CHOICE is the first head-to-head trial in RA patients who failed to biologic DMARDs,” Rubbert-Roth told Healio Rheumatology. “The key takeaway message is that, in a situation where a patient has active RA despite conventional DMARD treatment, and had previously failed to a biologic — which is most often a TNF inhibitor — their chance of achieving remission is higher with a JAK inhibitor versus a switch to a biologic with a different mode of action. This is why we chose abatacept, which has previously shown to be effective in TNF-[inadequate response] patients.”
“There were numerically more serious adverse events with upadacitinib compared to abatacept,” she added. “Data from head-to-head trials like SELECT-CHOICE provide the basis for physicians and patients for shared decision making to outweigh risk and benefits of different treatment options.”
Perspective
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Gary R. Feldman, MD, FACR
At week 12, upadacitinib demonstrated significant noninferiority as well as superiority and higher remission rates in comparison to abatacept. On comparison of the data from 12 to 24 weeks the variance between the treatment groups in all the components of the DAS28-CRP were reduced. At week 24 the calculated differences between the 2 agents’ change of each core component of the DAS28-CRP from baseline were: tender-joint count 4%, swollen-joint count 1%, patient’s global 5% and CRP 67%.
Because of a lack of a prespecified statistical plan for adjustment for multiple testing, there was no statistical analysis of the data from the core components. It is also stated in the footnotes that, “no clinical inferences can be drawn from these data.”
This randomized clinical trial found that upadacitinib at week 12 of therapy was significantly superior to abatacept both in reduction of disease activity and percentage of remissions as measured by change in DAS28-CRP in RA patients refractory to biologic DMARDs, but on calculating data of the core components of the DAS28-CRP at week 24 of therapy the margins of differences were reduced compared between the two agents. More serious adverse events were reported in the upadacitinib treated patients, notably cardiovascular and venous thromboembolic events.
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Teri Puhalsky, RN, CRNI
I am happy to see a trial like this: One class of medications vs. another, with patients that we see in practice who have not had the relief of their symptoms as we had intended. There is a long list of medication options for our patients, with more on the way, so it is essential to keep in mind the safety profile associated with them. We want the best outcomes for our patients, so adverse events and serious adverse events are important in helping the patient make an informed decision when choosing or changing drug therapy.
Is the benefit worth the risk? One way to reduce risk is to ensure that all the patient’s comorbidities are treated effectively. Gathering baseline data, joint counts and labs, and then regularly evaluating them, will allow us to determine efficacy. I am hopeful that more head-to-head medication trials are in the works with real-world patients. This type of study will assist us as we navigate a complicated disease process with many treatment options.
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