Roy M. Fleischmann, MD and primary investigator for SELECT-COMPARE, the phase III clinical trial of Rinovoq, AbbVie’s oral once-daily JAK inhibitor for adults with moderate to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. In this article the Rheumatology Network’s Amy Reyes interview’s Dr. Fleischmann, the clinical professor at the University of Texas Southwestern Medical Center in Dallas.
TrialSite News summarizes the discussion—follow the source below to read the entire interview.
What is Rinovoq (Upadactinib)?
Rinovoq (ABT-494) is a drug treatment for rheumatoid arthritis. It was approved by the U.S. FDA in August 2019. It was developed by AbbVie.
What is its Mechanism of Action?
The Janus Kinases (JAKs), a family of cytoplasmic tyrosine kinases, they function to transduce cytokine-mediated signals via the JAK-STAT pathway. There are four JAK subtypes, each of which has overlapping receptor responsibilities. Inhibitors of this enzyme family (Jakinibs) have shown efficacy in treating certain inflammatory and autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. However, the first generation of these drugs, tofacitinib, and ruxolitinib lacked subtype selectivity, affecting JAK1/JAK3 and JAK1/JAK2 respectively. This has led to dose-limiting side effects in the otherwise promising class of drugs. Upadacitinib is a second-generation Janus Kinases inhibitor that is selective for the JAK1 subtype of this enzyme over the JAK2 (74-fold), JAK3 (58-fold) and TYK2 subtypes.
The study titled “A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)” targeted 1,629 patients across up to 370 study sites. In Phase III randomized, double-blind study the sponsor sought to compare ABT-494 to Placebo and to Adalimumab in subjects with moderately to severely active rheumatoid arthritis who are on a stable background of Methotrexate (MTX) and who have an inadequate response to MTX.
Do JAK Inhibitors fill an Unmet Need?
Dr. Fleischmann notes that although TNF and IL-6 inhibitors are welcome additions for treatment plans and in many cases have worked well with patients not responding to methotrexate (or who cannot take this drug). However, there is a class of patient with active disease despite these options. He notes that JAKi has demonstrated a positive impact on patients who haven’t done well with TNF inhibitors such as adalimumab (HUMIRA). These oral monotherapies in most patients they are helping to meet the unmet needs of patients who cannot take methotrexate are adverse to interferons or who show a preference for oral medication. As they are effective prior to a TNFi, Dr. Fleishmann notes “they are a reasonable option as first-line post methotrexate or later in the paradigm.”
Call to Action: Follow the link below to read the rest of the interview with Dr. Fleischmann should you or a loved one have a Rheumatoid Arthritis diagnosis and think a second opinion may be beneficial.Source: Rheumatology Network