The 2015 ACR guideline for the treatment of rheumatoid arthritis recommends the use of TNF inhibitors before JAK inhibitors in patients who fail to respond adequately to conventional DMARD treatment. However, over the past several years, a growing amount of data suggests that JAK inhibitors may be more effective than TNF inhibitors for the treatment of RA. So, is it time to revisit that recommendation?
A pair of renowned experts in the field tackled that question on Friday, Nov. 6, during the ACR Convergence 2020 session The Great Debate: Janus Kinase Inhibitors Should/Should Not Be Used Before Biologics After Methotrexate Failure in RA. Registered attendees have on-demand access to watch a replay of the session through Wednesday, March 11.
Vibeke Strand, MD, argued in favor of the early use of JAK inhibitors, presenting data from various studies showing that patient-reported outcomes for pain and global assessment improve faster (2-3 days) and maximum response is achieved faster (approximately 3 months) for patients using JAK inhibitors than for patients taking biologics (approximately 6 months).
“The JAK inhibitor class is an exciting development for rheumatology and a broad variety of autoimmune diseases—and in RA, they should be used early,” said Dr. Strand, adjunct clinical professor in the Division of Immunology at Stanford University School of Medicine. “Based on phase three trials, responses are better in progressively earlier disease duration and less treatment-experienced patients. There’s well-established efficacy for this class in RA, based on head-to-head comparisons with one TNF inhibitor, which has indicated either equivalency or superiority.”
Additionally, she said, JAK inhibitors have the benefit of convenience, as they are administered orally, have a short half-life, adverse effects have been shown to often resolve over a short timeframe, and the risks have been well identified. She also noted that there is a need for vaccination, a careful patient history, attention to risk factors for venous thromboembolic events (VTEs) and arterial thromboembolism events, and surveillance for serious infections and malignancies.
Michael E. Weinblatt, MD, took the opposing side, saying that there is more long-term data supporting the use of TNF inhibitors and that more study is needed to support the safety and efficacy of JAK inhibitors in RA treatment. Dr. Weinblatt is the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, and R. Bruce and Joan M. Mickey Distinguished Chair in Rheumatology at Brigham and Women’s Hospital.
Dr. Weinblatt highlighted efficacy and toxicity concerns surrounding JAK inhibitors, including worries about venous thromboembolic events and increases in herpes zoster. Additionally, he argued that TNF-inhibitors appear to have a better record when it comes to treating RA in pregnant patients. Overall, he said, patient selection and cost are also key factors in determining which treatment approach to pursue.
“We have over 22 years of approved clinical experience with anti-TNFs and over 30 years of trial experience, whereas we only have eight years of approved clinical use of the jakinibs. And the cost — in Europe, the cost of an adalimumab biosimilar or etanercept biosimilar is about $5,000. The jakinibs in the U.S. are $50,000 to $60,000. So, there’s a major cost savings with biosimilars,” Dr. Weinblatt said. “In summary, you have equal efficacy, dose flexibility with the anti-TNFs, higher rates of zoster with the jakinibs and uncertainty regarding risk of VTE and [pulmonary embolism], and a requirement for laboratory monitoring with the jakinibs. To me, the choice is obvious.”