July 29, 2019
2 min read

Upadacitinib outperforms adalimumab in methotrexate-refractory RA

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Roy M. Fleischmann

Upadacitinib, a JAK1 inhibitor, is superior to adalimumab and placebo at improving signs, symptoms and physical function among patients with rheumatoid arthritis who have had an inadequate response to methotrexate, according to data published in Arthritis & Rheumatology.

“We have multiple medications for RA and the question now is in what order do we select them,” Roy M. Fleischmann, MD, of the University of Texas Southwestern Medical Center, told Healio Rheumatology. “This study evaluated the lower dose of upadacitinib — 15 mg vs. 30 mg — and compared its efficacy in combination with methotrexate, including clinical, functional and radiographic, to adalimumab in combination in methotrexate. The question posed is, ‘Which agent is effective in more patients after an incomplete response?’”

To analyze the efficacy and safety of upadacitinib (ABT-494, AbbVie), compared with adalimumab (Humira, AbbVie) and placebo, among patients with RA and an inadequate response to methotrexate, Fleischmann and colleagues conducted the SELECT-COMPARE trial. The global, double-blinded, phase 3 study included 1,629 adults evaluated at 286 sites in 41 countries. Participants were randomly assigned in a 2:2:1 ratio to receive either 15 mg of upadacitinib, 40 mg adalimumab or placebo each day, all while being treated with stable background methotrexate.

Primary endpoints included ACR20 and DAS28-CRP of less than 2.6 compared with placebo at week 12. In addition, the researchers assessed radiographic progression at week 26. Investigator-reported adverse events were collected and summarized up to week 26. An independent, blinded Cardiovascular Adjudication Committee reported on cardiovascular events, using predefined definitions, and deaths.

Image of arthritic hand 
Upadacitinib is superior to adalimumab and placebo for patients with RA who have had an inadequate response to methotrexate, according to data.

According to the researchers, both primary endpoints were met in patients treated with upadacitinib at week 12 (P .001), with ACR20 achieved by 71%, compared with 36% in the placebo group, and the DAS28CRP outcome demonstrated by 29%, compared with 6% in the placebo group. Upadacitinib demonstrated superiority to adalimumab in ACR50, as well as in changes in pain and the health assessment questionnaire disability index. Upadacitinib was also superior to adalimumab based on the percent of patients who achieved a DAS28CRP of 3.2 or less.

In addition, more patients treated with upadacitinib demonstrated low disease activity or remission, compared with both placebo and adalimumab (P .001). Radiographic progression was more inhibited, and observed in fewer patients, among those treated with upadacitinib compared with placebo (P .001).

Adverse events at week 26 included were comparable between the upadacitinib and adalimumab groups. The adalimumab group demonstrated the highest proportion of patients with serious adverse events and treatment-related discontinuation. Rates of herpes zoster and creatine phosphokinase elevations were highest among patients treated with upadacitinib. Three malignancies, five major adverse cardiovascular events, and four deaths were reported among participants, none of which occurred in the upadacitinib group. There were six venous thromboembolic events, including one in the placebo group, two among patients treated with upadacitinib and three in the adalimumab group.

“The results indicate that a better choice would be upadacitinib rather than adalimumab — both are effective, but upadacitinib is effective in more patients than adalimumab,” Fleischmann said. “In a patient with an inadequate response to methotrexate, it is very reasonable to consider upadacitinib as first-line therapy over adalimumab. If the patient has access to both medications, upadacitinib may be considered first because of efficacy as well as convenience, as it is oral.” – by Jason Laday

Disclosure : Fleischmann reports consulting and speaking fees, as well as honoraria, from AbbVie, Akor, Amgen, Celltrion, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi, Taiho and UCB. See the full study for additional authors’ disclosures.