SELECT-EARLY: Better RA outcomes with upadacitinib vs methotrexate
medwireNews: Treatment with the Janus kinase (JAK) inhibitor upadacitinib leads to significantly better clinical and radiographic outcomes than methotrexate therapy among patients with moderate-to-severe rheumatoid arthritis (RA) who have no or limited prior methotrexate exposure, show the SELECT-EARLY results.
“These head-to-head data provide consistent evidence of the efficacy of this JAK inhibitor versus the gold standard of initial RA therapy, supporting the potential of upadacitinib as a new therapeutic option for patients with RA,” say Ronald van Vollenhoven (Amsterdam University Medical Centers, the Netherlands) and co-investigators in Arthritis & Rheumatology.
The phase 3 trial included 945 patients with a median RA duration of 0.5 years (range 0–44 years) and risk factors for radiographic progression who were randomly assigned to receive 24 weeks of monotherapy with upadacitinib 15 mg or 30 mg once daily or methotrexate 7.5–20 mg once weekly. Less than 10% of participants had previously taken methotrexate, while around a quarter had received other conventional DMARDs, primarily sulfasalazine or hydroxychloroquine.
van Vollenhoven and colleagues report that ACR50 response rates at week 12 – the primary endpoint requested by the US FDA – were significantly higher among patients in the upadacitinib 15 mg and 30 mg groups compared with the methotrexate arm, at 52% and 56% versus 28%, respectively.
Similarly, a significantly higher proportion of upadacitinib- versus methotrexate-treated patients achieved the EMA-mandated primary endpoint of remission according to a DAS28-CRP score of less than 2.6 points at week 24, with corresponding rates of 48%, 50%, and 19%.
Both doses of upadacitinib were also associated with a significant reduction in radiographic progression compared with methotrexate, and the proportion of participants with no radiographic progression (mTSS score ≤0) at week 24 was significantly higher among those treated with upadacitinib 15 mg or 30 mg versus methotrexate (88 and 89 vs 78%).
Therefore, “[t]reatment with [upadacitinib] 30 mg was associated with minimal additional efficacy compared to 15 mg,” say the study authors. However, they note that the higher dose was associated with an increased risk for some treatment-emergent adverse events (TEAEs), including infections and serious infections.
Overall, 64.0%, 71.3%, and 65.3% of participants in the 15 mg, 30 mg, and methotrexate arms, respectively, experienced TEAEs. The corresponding rates of infection were 32.8%, 36.6%, and 32.8%, and rates of serious infection were 1.6%, 2.5%, and 1.3%.
There were six deaths in the study, including two in the upadacitinib 15 mg group, three in the 30 mg group, and one in the methotrexate group.
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