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Benefits of upadacitinib (Rinvoq) monotherapy versus methotrexate seen at the conclusion of the 48-week double-blind phase of a randomized clinical trial for rheumatoid arthritis (RA) persisted for 24 more weeks in an open-label extension.

At week 48, 20% improvements on the criteria of the American College of Rheumatology (ACR20) were seen in 74% of patients receiving upadacitinib 15 mg/day, and in 75% of those given this selective JAK inhibitor in dosages of 30 mg/day, compared with 57% of those randomized to methotrexate monotherapy in weekly doses up to 20 mg, according to Ronald van Vollenhoven, MD, PhD, of Amsterdam University Medical Center.

And at week 72, ACR20 responses for the 15- and 30-mg upadacitinib groups were 71% and 72%, compared with 50% of the methotrexate group, van Vollenhoven reported in a poster session at the .

The initially enrolled 945 methotrexate-naive patients with moderately to severely active RA and poor prognostic factors such as seropositivity for rheumatoid factor or anti-citrullinated peptide antibodies. It was conducted at 236 centers in 43 countries, and was sponsored by upadacitinib manufacturer AbbVie.

Patients' mean age at baseline was 54, and three-quarters were women. Median time since diagnosis was 0.5 years.

Mean baseline Disease Activity Score in 28 joints (DAS28) was 5.9, and in 78% the DAS28 was above 5.1, indicating high disease activity. Tender and swollen joint counts were 25 and 17, respectively, and the mean pain score on a 100-point visual analog scale was 66.

A total of 781 patients completed the 48-week double-blind phase, and 775 entered the long-term extension phase. Among the 7% of patients who discontinued treatment during the extension phase, the most common reasons were because of adverse events (2.1%), withdrawal of consent (1.5%), and lost to follow-up (1.3%).

After week 48, treatment was open-label. For patients who had not achieved remission on the Clinical Disease Activity Index (≤2.8) by week 26, rescue therapy was provided, which was methotrexate for the upadacitinib groups and upadacitinib for the methotrexate group.

Already at week 12, ACR50 responses were reported in 52% of the 15-mg group, which is the approved dosage, and 56% of the 30-mg group, compared with 28% of those in the methotrexate group.

Other outcomes at week 72 included 50% improvement, which were 62% and 67% in the 15- and 30-mg groups, respectively, compared with 39% for placebo, while for 70% improvements, the responses were 47% and 54% versus 26%.

Week 72 DAS28 scores below 3.2 and 2.6, indicating low disease activity and remission, respectively, were observed in 63% and 52% of the 15-mg group and in 69% and 61% of the 30-mg group, compared with 38% and 28% of the methotrexate group.

Also at that time point, Clinical Disease Activity Index scores of 10 or lower were seen in 60% of the 15-mg group and 69% of the 30-mg group compared with 42% of the methotrexate group, while scores of 2.8 or lower were observed in 35%, 44%, and 19%, respectively.

"The efficacy of upadacitinib was underscored by the fact that about one-third of patients achieved remission according to the very strict ACR/European League Against Rheumatism Boolean remission," van Vollenhoven said during his poster presentation.

Serious adverse events and adverse events leading to discontinuation were similar across the three groups. Higher rates of herpes zoster were seen in the upadacitinib groups, at 5.6 and 5.2 per 100 patient-years in the 15 - and 30-mg groups compared with 1.1 per 100 in the methotrexate group. There also were more cases of elevated creatine phosphokinase among the upadacitinib groups.

Two patients in the methotrexate group developed a venous thromboembolic event, as did one in the 30-mg group but none in the 15-mg group.

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