Jenna Dvorin

—an investigative, small-molecule, oral JAK1-selective inhibitor&mdash;proved superior to adalimumab (ADA) or a placebo (PBO) in inhibiting rheumatoid arthritis’ radiographic progression up to 26 weeks, according a new study.

While it hasn’t been formally approved yet, upadacitinib is critical to ongoing trials in treating psoriatic arthritis, Crohn’s disease, atopic dermatitis, and ulcerative colitis, alongside being considered for treating ankylosing spondylitis and giant cell arteritis. UPA was also granted 

 by the US Food and Drug Administration (FDA) in 2018.

The SELECT-COMPARE study randomized 1629 patients to once-daily UPA 15 mg (n= 651), PBO, or ADA 40 mg (n= 327) every other week, alongside background methotrexate (MTX). From weeks 14-26, patients switched treatments if they saw less than 20% improvement in tender/swollen joint count or if the Clinical Disease Activity Index was greater than 10.

Before week 26, efficacy was judged via non-responder imputation and binary endpoints; after week 26, last observation carried forward determined continuous and binary endpoints.

Regarding patients on UPA, 38.7% were switched between weeks 14 and 16, but of those who remained on UPA, 86% completed week 48 of the study. Patients on ADA, on the other hand, saw 48.6% switched between weeks 14 and 26, and of those who remained, only 76% completed week 48. Those who did not complete the study largely exited due to actual or predicted adverse events.

Cumulative exposures were 1243.3 patient-years (PYs) for UPA and 467.8 PYs for ADA. At week 26, week 48, and additional checkpoints, UPA was significantly more effective at improving signs and symptoms based on the rheumatoid arthritis classification criteria ACR scale, and achieving clinical remissions based on Disease Activity Score 28 C-Reactive Protein.

UPA also slowed radiographic progression far more effectively than the placebo in weeks 26-48. UPA even had a lower rate of adverse events than did ADA, with the exception of Herpes zoster.

"These data continue to support the potential of upadacitinib to help maintain consistent disease control for patients living with moderately to severely active rheumatoid arthritis," said Professor Ronald van Vollenhoven, MD, PhD, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands, in a statement.

These results further confirm the additional integrated safety analyses, which took place across 5 SELECT phase 3 studies.

"While remission is the primary treatment goal, in accordance with the American College of Rheumatology and the European League Against Rheumatism recommendations, a majority of patients do not achieve clinical remission today, despite currently available treatment options," van Vollenhoven said.

The study was funded by global biopharmaceutical company AbbVie, which also discovered and developed upadacitinib. Marek Honczarenko, MD, PhD, vice president of Immunology Development at AbbVie, said the study adds to the past decade of critical advances in understanding RA management—and the pursuit of achieving patient remission.

"As data continue to emerge from the SELECT program, we look forward to deepening our understanding of the benefits and risks of JAK inhibition on treatment outcomes in different patient populations with moderately to severely active rheumatoid arthritis," Honczarenko said.

The study was presented at the 2019 European Congress of Rheumatology (EULAR).

Articles

A new study of AbbVie’s original JAK1-selective inhibitor indicates that it outdoes adalimumab without sacrificing safety in rheumatoid arthritis treatment.

Upadacitinib Better than Adalimumab in Rheumatoid Arthritis

Results from the SPIRIT-H2H study indicate that in patients with active psoriatic arthritis, ixekizumab (Talz) is superior to adalimumab (Humira) in the proportion of patients who simultaneously reduced disease activity by ≥50% and achieved complete skin clearance.

The research was presented at a late-breaking session at the European Congress of Rheumatology (EULAR 2019) in Madrid, Spain, by Philip Mease, MD, Swedish Medical Center/Providence St. Joseph Health and University of Washington.

“In the SPIRIT-H2H trial, Taltz demonstrated effectiveness in improving the signs and symptoms of active psoriatic arthritis,” said Mease. “Head-to-head data like these are significant and help inform treatment decisions. This study underscores that Taltz is an important option for healthcare providers to consider for their patients.”

The assessor-blinded SPIRIT-H2H study included 566 patients who were naïve to biologic disease-modifying anti-rheumatic drugs (bDMARDs) and inadequately responded to conventional synthetic DMARDs. Of those, 465 participants had active psoriatic arthritis and were randomized to either ixekizumab (n = 234) or adalimumab (n = 231) at the FDA-approved doses for those treatments for 52 weeks. The study also included 101 patients with moderate to severe plaque psoriasis who were randomized to ixekizumab (n = 49) or adalimumab (n = 52) at the approved dose for psoriasis.

Meeting the primary endpoint, at 24 weeks, 36% of patients receiving ixekizumab had achieved both disease activity reduction of ≥50% according to the American College of Rheumatology (ACR50) and complete skin clearance as measured by the Psoriasis Area and Severity Index (PASI 100) compared to 28% for adalimumab (

“For patients with active psoriatic arthritis, it’s important to find a treatment that is effective and consistent in alleviating the debilitating joint symptoms, while also improving skin clearance,” said Christi Shaw, president of Lilly Bio-Medicines.

However, ixekizumab was not superior for both ACR50 and PASI 100, when the endpoints were analyzed separately. Patients taking ixekizumab were significantly more likely than those taking adalimumab to achieve PASI 100 (60% vs 47%; 

 <.01) at 24 weeks, while the difference in ACR50 was not significant between groups (51% vs 47%).

Ixekizumab was found statistically significantly superior to adalimumab for several secondary endpoints at week 24 including, PASI 75 (80% vs 69%), PASI 90 (72% vs 56%), minimal disease activity (48% vs 35%), and Psoriatic Arthritis Disease Activity Score very low disease activity (PASDAS VLDA <1.9; 29% vs 19%)(

The safety results for ixekizumab were similar to previous studies with no new signals observed. The most frequent adverse reactions for ixekizumab and adalimumab were infections (36.0% vs 30.7%, respectively), injection site reactions (9.5% vs 3.2%), allergic/hypersensitivity reactions (2.5% vs 3.9%) and cerebrocardiovascular events (1.1% vs 1.8%).

The US Food and Drug Administration (FDA) approved 

ixekizumab for the treatment of psoriatic arthritis

 in December 2017. Adalimumab was first approved in 2002 for rheumatoid arthritis and the label has since been expanded to include indications for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult and 

, ulcerative colitis, plaque psoriasis, hidradenitis suppurative, and uveitis.

Multicentre, Randomised, Open-Label, Assessor-Blinded, Parallel-Group Head-to-Head Comparison of the Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients with Psoriatic Arthritis Naive to Biologic Disease-Modifying Anti-Rheumatic Drugs: 24-Week

,” was presented on June 14 at EULAR 2019.

Ixekizumab (Talz) was significantly more likely to both reduce disease activity by ≥50% and achieve complete skin clearance than adalimumab (Humira).