When treating rheumatoid arthritis, establishing insurance coverage guidelines regarding transitions between Janus kinase (JAK) inhibitors is urgently needed, a local rheumatology expert said. 

Professor Lee Sang-heon of the Rheumatology Department at Konkuk University Hospital spoke on the latest treatment guidelines for rheumatoid arthritis and shared data from clinical studies of JAK inhibitors at a media session by AbbVie Korea last Friday.

According to Lee, reimbursing such switching therapy is necessary because patients may develop resistance after long-term use or unsuccessful administration of JAK inhibitors.

"There's an upward trend in the number of rheumatoid arthritis patients in Korea, yet there remains a significant unmet need in achieving remission and pain control," Lee said. "Specifically, there are no current reimbursement guidelines for switching between JAK inhibitors."

Lee stressed that he believes that upcoming research findings and clinical evidence will necessitate a reimbursement criteria update.

According to Lee, JAK inhibitors are a safe therapeutic option, particularly drawing attention to the fact that JAK inhibitor Pfizer's Xeljanz (ingredient: tofacitinib) – first introduced in 2013 – has demonstrated safety.

The emphasis comes in light of a setback Xeljanz faced in the domain of safety in the past.

Previously, in 2021, during the ORAL Surveillance clinical trial, cardiovascular issues associated with Xeljanz arose. Compared to tumor necrosis factor (TNF) inhibitors, there were detected risks of myocardial infarction, stroke, major cardiovascular events, and cancer.

However, Lee highlighted that upon reviewing additional safety data, tofacitinib showed virtually no significant difference in cardiovascular risks compared to TNF inhibitors.

"While a slight increase in risks was observed, it was deemed statistically insignificant," Lee said. "Furthermore, a clinical study focusing on Korean rheumatoid arthritis patients found no significant difference in the risk of myocardial infarction, stroke, cardiovascular-related mortality, major cardiovascular events, or cancer rate between JAK inhibitors and TNF inhibitors."

In contrast, the clinical benefits offered by JAK inhibitors are seen as substantially more significant, he added.

Lee noted that in patients who showed an inadequate response to methotrexate (MTX) or targeted anti-rheumatic drugs (csDMARD/bDMARD), AbbVie's Rinvoq demonstrated approximately 20 percent improved treatment response rates.

"If rheumatoid patients can achieve better therapeutic responses, it can significantly reduce the risks of comorbidities associated with rheumatoid arthritis, including cardiovascular events," he said. "This suggests that JAK inhibitors can play a pivotal role in reducing cardiovascular complications in these patients."

Lee explained that this is why there is an increasing demand for establishing guidelines to switch between different JAK inhibitors.

Currently, there are four approved JAK inhibitors for rheumatoid arthritis in Korea -- Pfizer's Xeljanz, Eli Lilly's Olumiant, AbbVie's Rinvoq, and Galapagos Jyseleca.

Xeljanz inhibits JAK1, JAK2, JAK3, and TYK2, Olumiant targets JAK1 and JAK2, and Rinvoq and Jyseleca selectively inhibits JAK1.

"This means that each drug has a slightly different mechanism of action," Lee said. "As a result, there is frequent switching between these drugs overseas, primarily because prolonged use of one drug may lead to increased resistance."

Although overseas clinical settings permit switching between JAK inhibitors, in Korea, if a patient fails one JAK inhibitor, they cannot transition to another, as there are no established payment standards for such a switch, he added.

Lee further mentioned research indicating that switching from one JAK inhibitor to another resulted in a longer drug persistence compared to TNF inhibitors.

"The primary reason for not allowing switches between JAK inhibitors is the lack of substantial clinical evidence," Lee said. "As JAK inhibitors are relatively new, related literature and research are limited."

However, it is rumored that if sufficient evidence is presented, health authorities will actively consider allowing switching, he added.

Lee concluded that, fortunately, a research paper on this topic is set to be published next year, and with that evidence, Korea can push for changes in the reimbursement guidelines.

Meanwhile, during the session, Lee also highlighted the complexity of rheumatoid arthritis.

"Rheumatoid arthritis often coexists with other conditions such as hypertension, hyperlipidemia, diabetes, angina, and depression," he said. "Approximately 53 percent of all rheumatoid arthritis patients suffer from these associated illnesses."

He recalled that earlier in his career, the treatment goal was simply managing pain using aspirin. However, recent immunological research has paved the way for the development of various treatment drugs.

"Primary treatment objectives for treating rheumatoid arthritis nowadays is about achieving remission," Lee said. "If this is unattainable, maintaining low disease activity (LDA) becomes the goal."

Around 40 percent of patients currently achieve remission, while the rest are in the LDA category, he added.