Upadacitinib superior to placebo, adalimumab in active RA on methotrexate
CHICAGO — Among patients with rheumatoid arthritis who experienced an inadequate response to methotrexate, a daily 15-mg dose of the JAK1 inhibitor upadacitinib was superior to both placebo and adalimumab at improving disease signs and symptoms.
Additionally, upadacitinib was associated with significantly lower radiographic progression compared with placebo, according to results presented here by Roy Fleischmann, MD, of University of Texas Southwestern Medical Center at Dallas.
Fleischmann and colleagues conducted SELECT-COMPARE, a phase 3, randomized, double blind study, to analyze the safety and efficacy of upadacitinib (ABT-494, AbbVie) compared with placebo and adalimumab in patients with active RA despite treatment with methotrexate (n = 1,629).
Patients were randomly assigned 2:2:1 to once-daily upadacitinib at 15 mg, placebo or 40 mg of adalimumab every other week. All patients continued stable background methotrexate.
Primary outcomes were ACR20 and number of patients who achieved Disease Activity Score 28-joint count C-reactive protein (DAS28CRP) less than 2.6 (NRI) at 12 weeks. Secondary outcomes included noninferiority and superiority of upadacitinib compared with adalimumab at 12 weeks, as well as radiographic inhibition for upadacitinib vs. placebo at 26 weeks. Patients whose improvement in tender joint count and swollen joint count was less than 20% were rescued between weeks 14 and 26 — from placebo to upadacitinib, upadacitinib to adalimumab or adalimumab to upadacitinib.
The study met all primary and secondary outcomes, and 91% of patients completed the trial through week 26.
ACR20 and DAS28CRP less than 2.6 were reached by significantly more patients assigned to upadacitinib compared with placebo (70.5% vs. 36.4% achieved ACR20 and 28.7% vs. 6.1% achieved DAS28CRP < 2.6) at week 12. Additionally, upadacitinib met superiority vs. adalimumab at 12 weeks — and maintained through week 26 — for ACR50 (45.2% vs. 29.1%), DAS28CRP 3.2 or less (45% vs. 28.7%), change from baseline in pain (–31.76 vs. 25.31) and change from baseline in health assessment questionnaire disability index (–0.6 vs. –0.49).
At study end, radiographic progression occurred among significantly fewer patients assigned to upadacitinib compared with placebo (change in mTSS was 0.24 vs. 0.92). Similarly, more patients assigned to upadacitinib had no radiographic progression compared with those assigned to placebo (change in mTSS 0 was 83.5% vs. 76%).
Though the rate of adverse events and serious infections was higher among patients assigned to upadacitinib compared with placebo, it was similar to the rate among patients assigned to adalimumab. Herpes zoster was the most common infection in the upadacitinib group vs. the placebo and adalimumab groups. Of the three malignancies, five major adverse cardiovascular events and four deaths reported, none occurred in the upadacitinib group. Venous thromboembolism occurred among one patient assigned to placebo, two assigned to upadacitinib and three assigned to adalimumab.
“The take-away is that ... this is the second trial where JAK is superior to adalimumab, and it really raises the question, in a methotrexate incomplete responder, ‘What’s the best drug to use, assuming access is equal, which it never is?’,” Fleischmann told Healio Rheumatology. “It may be that this class — the JAK class — is actually better than the biologic class. I’m sure there will be other studies that will look at this, but the first few studies would suggest that [it is], and I think that’s very important.” – by Stacey L. Adams
Disclosure: Fleischmann reports relationships with AbbVie, Lilly, Gilead and Pfizer. Please see the study for all other authors’ relevant financial disclosures.
Fleischmann R, et al. Abstract 890. Presented at ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.