They’ve been approved for the US market since 2012, but Janus kinase (JAK) inhibitors are still the new kid on the block in terms of rheumatoid arthritis treatment. As such, the real-world evidence on this class of drugs is scarce compared to established treatments.
Now, researchers in Japan have taken an important step in changing that, using extensive patient data to show that JAK inhibitors are as effective a first-line treatment as existing medications, even though they’re still largely considered a back-up plan if others fail.
“Real-world patients have different characteristics compared with the patients recruited in randomized controlled trials,” the researchers note in the study. “Therefore, it is important to investigate the effectiveness and safety of JAK inhibitors in real-world settings.”
Analyzing the data of 622 patients from the ANSWER cohort study, the scientists evaluated four JAK inhibitors; baricitinib (BAR) known in the US as Olumiant, tofacitinib (TOF) known as Xeljianz, and upadacitinib (UPA) known as Rinvoq. They also assessed peficitinib (PEF), or Smyraf, which is predominantly available in Japan and Southeast Asia.
“We found that most patients have success with these medications, and the efficacy and safety of each of these JAK inhibitors was not significantly different in the treatment of rheumatoid arthritis,” says lead author Dr Shinya Hayashi, a arheumatology specialist at Kobe University. “These medications offer options when biologic disease-modifying antirheumatic drugs (DMARDS) have failed.”
JAK inhibitors interrupt signals that cause inflammation. With rheumatoid arthritis, the body makes too many proteins called cytokines, which play a key role in inflammation. When these cytokines attach to immune cell receptors, the message is given to make even more of the proteins. JAK inhibitors block this messaging pathway, which calms the immune system response and, in turn, relieves painful arthritis inflammation.
JAK inhibitors are also effective for treating skin conditions such as eczema and vitiligo, and there are now around a dozen different types approved for use in the US.
Traditionally, the first treatment for rheumatoid arthritis is usually injections of methotrexate, a DMARD. Then, if the drugs don’t do the trick, or they come with too many side effects, a patient may then be switched to an orally administered JAK inhibitor. The patients in the study had received the JAK inhibitor following poor responses to DMARDs.
But because they’re a newer class of medication, much like glucagon-like peptide 1 (GLP-1) agonists for weight loss, they are often considered a ‘when all else fails’ plan B. Doctors generally prescribe DMARD biologics first, because there’s more long-standing research available on these.
The researchers, assessing the data with various pain-indicator surveys, found that around 90% of the 622 patients were still taking their JAK inhibitors six months after beginning them.
Overall, about one-third of patients saw their arthritis enter remission within the six months, with more than 80% experiencing ‘low disease activity,’ in which symptoms were largely controlled.
The hesitancy in JAK inhibitors uptake has been due to concerns about real-world efficacy beyond controlled trials – which this study lays to rest – and potential side effects.
While the researchers say the study has its limitations, such as six months being a short time frame for long-term side effects, and a lack of studies comparing all classes of drugs, the four JAK inhibitors performed similarly to each other, and their effectiveness proved to be on par with existing DMARDs. A previous clinical study, showed they had comparable efficacy to TNF inhibitors, another type of DMARD.
Around 1.3 million Americans have rheumatoid arthritis, a chronic autoimmune condition that can greatly diminish quality of life and prove stubborn to treat.
The study was published in the journal Rheumatology.