Elsubrutinib, upadacitinib combination lowers lupus activity through 104 weeks
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WASHINGTON — A drug combining elsubrutinib with upadacitinib led to lower disease activity for up to 104 weeks in patients with moderately to severely active systemic lupus erythematosus, according to data presented at ACR Convergence 2024.
“ABBV-599 is a combination of two drugs: one is elsubrutinib, which is a selective Bruton tyrosine kinase inhibitor, and a drug familiar to most of you, upadacitinib, which is a Janus kinase inhibitor primarily selective for JAK-1,” Joan T. Merrill, MD, of the Oklahoma Medical Research Foundation, told attendees.
In a previously reported phase 2 study that assessed different combinations of the drugs for patients with SLE, two combinations brought statistically significant improvements in various endpoints at 48 weeks: Upadacitinib (Rinvoq, AbbVie) alone at 30 mg and the higher-dose version of ABBV-599 (AbbVie), which consisted of upadacitinib 30 mg plus elsubrutinib (AbbVie) 60 mg, Merrill said.
For a longer-term assessment, Merrill and colleagues conducted a long-term extension study through 104 weeks. The study included 127 patients with SLE, including 45 on the combination drug, 47 on upadacitinib alone and 35 initially placebo-treated patients who were switched to the combination. The researchers examined efficacy using the SLE Responder Index (SRI-4), BILAG-based Combined Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS), as well as mean glucocorticoid doses and flares.
According to the researchers, the proportions of patients who achieved SRI-4 continued increasing through week 104, rising to 85.4% (95% CI, 74.5-96.2) among patients on ABBV-599, 82.1% (95% CI, 70-94.1) in patients using upadacitinib 30 mg, and 61.3% (95% CI, 44.1-78.4) among those switched from placebo.
Similar results were observed with the BICLA endpoint, according to Merrill. Response rates were 78% (95% CI, 65.4-90.7) for ABBV-599, 69.2% (95% CI, 54.7-83.7) for upadacitinib 30 mg, and 54.8% (95% CI, 37.3-72.8) for the placebo switch group.
“You can see really the same pattern — that the placebo group didn’t make it back up there after they got switched to active combination treatment, but there was sustained improvement over the entire period for the two dosing groups that had started out that way,” Merrill said.
Meanwhile, secondary endpoints, including LLDAS and flares per patient-years, were improved or maintained. Glucocorticoid usage was nearly zero in all three groups by week 104.
There were treatment-emergent adverse events among 75.6% of patients on ABBV-599, in 66% of those using upadacitinib 30 mg, and in 85.7% of those switched from placebo, according to the researchers.
“In the first part of the trial, it was roughly 80% to 85% of the patients who had treatment-emergent adverse events,” Merrill said. “I don’t want to make anything out of it being that much better, but certainly it is not worse. As for things that you think about when you’re looking at this class of drugs, there’s just no signal here of any major danger from tuberculosis, malignancy. We saw some non-melanoma skin cancer in one patient, which got excised, and they were fine.
“In patients with moderately to severely active lupus, either upadacitinib 30 mg alone, or the combination treatment of that with elsubrutinib 60 mg, resulted in lower disease activity, and it was sustained throughout the second part of the trial,” she added.
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Merrill J. Abstract #2577. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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