JAK Inhibitor Achieves Important Milestone in RA

The JAK inhibitor upadacitinib has been shown to lead to significant improvements in clinical, radiographic, and patient-reported outcomes as monotherapy as compared to patients who were treated with methotrxate, shows a newly published study in Arthritis and Rheumatology.

The study, which was sponsored by AbbVie, included 947 patients with moderately to severely active rheumatoid arthritis who were treatment naive or had little exposure to methotrexate as first-line therapy. They patients were randomized to once-daily upadacitinib at 15 mg or 30 mg or to weekly methotrexate (7.5–20 mg per week for 24 weeks) with 89% of patients completeing the full 24 weeks.

Both groups met the primary endpoint of ACR50 at week 12 with 52% and 56% of the treatment groups achieving ACR50 as compared to 28 percent of patients who received methotrexate. (P<0.001).

And, 48 percent and 50 percent of patients, respectively, achieved a 28-joint Disease Activity Score including C-reactive protein (DAS28, CRP) of less than 2.6 at 24 weeks as compared to 19 percent of patients treated with methotrexate.

"Statistically significant and clinically meaningful improvements in multiple patient-reported outcomes were recorded with both upadacitinib doses versus methotrexate. Overall, 88% and 89% of upadacitinib 15 mg and 30 mg patients had no radiographic progression (mTSS of less than zero; methotrexate: 78%; at least P<0.01). Through week 24, the frequency of treatment-emergent adverse events was similar between the methotrexate (65%) and upadacitinib 15mg arms (64%), but slightly higher in the upadacitinib 30 mg arm (71%)," the authors wrote.

This the first study to report a JAK-inhibitor achieving Boolean remission by week 24 in 24–25 percent of methotrexate-naïve patients.

This study, called SELECT-EARLY, was designed to study the safety and efficacy of upadacitinib as monotherapy in patients with moderately to severely active rheumatoid artritis and poor prognostic features who are either naïve or have limited exposure to methotrexate. The study was led by Ronald van Vollenhoven, of Amsterdam University Medical Centers, The Netherlands.