Evolving insights on JAK inhibitors for rheumatoid arthritis management
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Key takeaways:
- Understanding of the safety and efficacy of JAK inhibitors continues to evolve.
- Real-world data sheds light on adverse events.
Physician understanding about the safety and efficacy of Janus kinase inhibitors for patients with rheumatoid arthritis has evolved with real-world and clinical trial data.
RA is a progressive and chronic inflammatory disorder that causes damage to the synovial lining of the joints. Patients with untreated RA can have persistent pain, inflammation and swelling of the joints, as well as deformities and loss of manual function in certain parts of the body.
Janus kinase (JAK) inhibitors are small-molecule oral treatments available for patients with RA. JAK inhibitors are a disease-modifying anti-rheumatic drug that offer an effective, long-term option for patients with RA.
Exploring more feasible treatments and alternatives has led to JAK inhibitors becoming one of the first novel targeted therapies for patients with RA, according to Jeffrey A. Sparks, MD, an associate professor of medicine at Brigham and Women’s Hospital and Harvard Medical School. Methotrexate has been the first-line choice DMARD for 90% of patients with moderate or severe RA. Biologic therapies with TNF inhibitors have also been used in the past.
Physician understanding of JAK inhibitors for treatment of RA continues to evolve to address the unmet needs of patients with RA. MTX injections may not be desirable for patients and TNF inhibitors demonstrate a significant association with psoriasis. Loss of response or intolerability has also been reported by patients with RA undergoing treatment with MTX and TNF inhibitors.
There are currently three JAK inhibitors approved for the treatment of RA in the United States: tofacitinib (Xeljanz, Pfizer), upadacitinib (Rinvoq, Abbvie) and baricitinib (Olumiant, Eli Lilly & Co.).
JAK inhibitors are oral medications and may be easier to administer to patients, said Sparks. The retention rates of patients prescribed JAK inhibitors for RA remains high.
“JAK inhibitors are quite effective and have a quick onset of action,” said Sparks. He emphasized the importance of implementing adherence strategies to improve retention rates of patients with RA.
With the use of JAK inhibitors, patients may notice a quick improvement and be motivated to continue taking the medication. However, they may also be a bit less likely to adhere, particularly compared with infusion drugs, Sparks said.
“Adherence strategies are needed across all medications in rheumatology, including JAK inhibitors. It has helped that most JAK inhibitors are now administered once daily,” he said.
Real-world data is an important adjunct to clinical trial data for JAK inhibitors. According to Sparks, “real-world studies may find signals for adverse events that could not be detected in trials that typically have small sample size and short follow-up. There are some subgroups at higher risk of poor outcomes, including risk of shingles, venous thromboembolism, cardiovascular disease, and cancer.”
“It will take more education about the importance of the medication to optimize retention rates,” said Sparks. “The ORAL Surveillance trial was one of the most important safety studies ever conducted in RA. It had a very large sample size, an active comparator group and lengthy follow-up.”
The ORAL Surveillance (ORALSURV) trial was an FDA-mandated phase 3b/4 study assessing the risk of major adverse cardiovascular events (MACE) and malignancies. The trial compared tofacitinib with anti-TNF therapy in older patients with RA who had cardiovascular risk factors.
According to researchers, “major adverse cardiac events were reported in 47 patients in the 5 mg tofacitinib group, 51 patients in the 10 mg group and among 37 participants receiving a TNF inhibitor.”
“This [ORALSURV] did not reach the pre-specified metrics to establish non-inferiority of the JAK inhibitor tofacitinib compared to TNF inhibitors for the outcomes of cardiovascular disease and cancer,” Sparks said. “However, the effect sizes were quite modest and the trial was enriched for people who had risk factors for these outcomes.”
More studies and information are needed on JAK inhibitors, but Sparks is sure this is only the beginning.
“I would like to see JAK inhibitors investigated for other rheumatic diseases and to evaluate whether JAK inhibitors other than tofacitinib have risks of cardiovascular disease and cancer,” he concluded.
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