Latest JAK Inhibitor Shows RA Improvement Over Older Biologic Treatment

The results from a new trial comparing the efficacy and safety of upadacitinib (Rinvoq) to abatacept (Orencia) for treating rheumatoid arthritis patients was recently published in the New England Journal of Medicine.

In a six-month-long Phase 3 clinical trial, patients with RA refractory to biologic disease-modifying anti-rheumatic drugs (DMARDS) — or in other words, patients who didn’t experience significant improvement on biologic treatments — were given either upadacitinib (303 patients) or abatacept (309 patients) in a double-blind study.1

The researchers tracked their RA with a composite Disease Activity score and C-reactive protein (CRP) testing.1

How upadacitinib and abatacept compared

They found greater improvement for the patient’s RA who took upadacitinib versus abatacept with the percentage of remission in the first group reaching 30 percent versus 13 percent.1

However, patients taking upadacitinib experienced more serious adverse events with one death, one nonfatal stroke, and two venous thromboembolic events. More patients in this group also had higher abnormal liver function tests.1

Two RA treatments, two different modes of action

The two drugs examined in this study work by two very different approaches to the immune system, despite having the same goal of calming RA inflammation.

Abatacept is a biologic administered by infusion that blocks T-cells in the immune system, also referred to as an immunomodulator. Through this process, it reduces inflammation signals in the body. This biologic has been around for a while as it was approved to treat RA in late 2005.

Upadacitinib was approved in August 2019, so it is one of the latest new treatments for RA. It is one of three treatments belonging to the new drug class called JAK (Janus kinase) inhibitors (not a biologic) that targets a type of cytokine or chemical pathway for inflammation. It is taken orally as a pill.

Side effects to consider regardless of treatment type

Like just about all DMARD treatments for RA, both these drugs lower the immune system, which can increase the risk for serious infection. Upadacitinib can also increase the risk for deep vein thrombosis, pulmonary embolism, and stroke in general. JAK inhibitors as a group also have shown this, along with the increased risk of gastrointestinal (stomach or intestines) tears, increased cholesterol, and increased liver enzymes.

Unfortunately, all RA treatments have side effects and increased health risks — cancer is a commonly known one. With this in mind, patients often have to try medications for a period of time and monitor how their bodies react while under the care of watchful rheumatologists.

My refractory RA experience

In my case, I tried two biologics and one JAK inhibitor before I found a treatment that proved effective for my refractory case of RA. Only the third biologic showed the kind of significant results we look for with improved symptoms and a CRP in the normal range.

I also struggled with different side effects from the treatments. For me, the JAK inhibitor I took gave me uncomfortable stomach issues and chronic headaches. After several months I felt my body was telling me that it wasn’t a good fit, so I moved on.

RA treatment challenges

Many people with RA cycle through many more treatments than I did before landing on something that works for them. (It’s important to note that I was diagnosed as a child more than 40 years ago, so biologics were not available for at least the first half of my illness. Then I had other health issues that delayed me from trying biologics to treat my RA.)

A second challenge is that patients frequently have the experience that a treatment will work for a while, like a year or two, then fade in effectiveness. Why is a mystery, but I often wonder if the body adapts or the RA finds a workaround in order to do its voodoo once again.

Encouraging signs for RA treatment

The results of this new clinical trial are very encouraging because it looked at patients with difficult-to-treat RA by comparing an older biologic to a new treatment (JAK inhibitor). The findings are encouraging for the ongoing improvement in treatment, along with potentially easing the methodology of taking a pill versus a time-consuming infusion (or injection). While everyone reacts differently to treatment, the success numbers from this study speak for themselves as far as the potential benefits.

It’s my belief that if patients have found something that works for them, they should stick with it. But positive results like these show me that ongoing discussions with the rheumatologist are important for exploring treatment options should what I am on begin to fail.

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