Two hands viewed in X-ray format showing red areas of inflammation around the joints to indicate arthritis or rheumatic disease
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Real world research led by the Kobe University Graduate School of Medicine in Japan shows that Janus kinase (JAK) inhibitors are effective, non-invasive treatments for rheumatoid arthritis with manageable side effects.

In the U.S., around 1.3 million people have rheumatoid arthritis and have to live with the chronic autoimmune condition, which leads to progressive joint damage if left untreated. While a number of different therapeutic options are available such as biological disease-modifying antirheumatic drugs (DMARDs), they do not work for all patients, are associated with significant side effects and often become ineffective over time.

“The use of biological DMARDs such as TNF-alpha inhibitors and IL-6 inhibitors enable the achievement of low disease activity and remission in rheumatoid arthritis patients. However, biological DMARDs are administered through the subcutaneous or intravenous route owing to high molecular weights and often cause secondary ineffectiveness,” wrote lead researcher Shinya Hayashi, Kobe University Graduate School of Medicine, and colleagues in the journal Rheumatology.

“Recently, JAK inhibitors that are orally administered low molecular weight compounds were developed and used for the treatment of rheumatoid arthritis patients.”

JAK inhibitors can regulate immune responses and are therefore useful for the treatment of autoimmune diseases, skin conditions and some cancers. At least 12 such drugs have been approved by the U.S. FDA to treat a range of different conditions including rheumatoid arthritis.

Despite this, there has been discussion about how effective JAK inhibitors really are for treating a wide range of patients as they tend to be used mostly in patients who cannot tolerate other therapies such as DMARDs.

“The efficacy and safety of these JAK inhibitors were generally analyzed in randomized controlled trials. However, in real-world settings, JAK inhibitors are usually used in patients with intolerance to methotrexate due to comorbidities or with multiple biological DMARD failures,” explain the authors.

“Real-world patients have different characteristics compared with the patients recruited in randomized controlled trials. Therefore, it is important to investigate the effectiveness and safety of JAK inhibitors in real world settings.”

In this study, 622 patients were selected from the ANSWER cohort study, an observational, multicenter registry of patients with rheumatoid arthritis in Japan. Those included were treated with four different JAK inhibitors: tofacitinib, baricitinib, peficitinib or upadacitinib, after first being treated with other medications such as biological DMARDS and methotrexate.

The overall health and disease activity of the patients was assessed six months after starting treatment with the JAK inhibitors. Retention rates for those treated with tofacitinib, baricitinib, peficitinib or upadacitinib were similar at six months at 87%, 90%, 83% and 83%, respectively. Discontinuation due to adverse events in the respective groups was 9%, 5%, 7% and 6%.

Notably, around one in three patients had achieved disease remission at six months, with 75% reaching low disease activity if not complete remission. No major differences between the groups were seen for efficacy rates.

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