JAK Inhibitors: How This New Rheumatoid Arthritis Treatment Works

Rheumatoid arthritis (RA) is an autoimmune disease, meaning it’s caused by an overactive immune system. Instead of just attacking harmful viruses and bacteria, an immune system with RA attacks your synovium—the protective space between joints.

The synovium is like a cushion between joints, and it creates a fluid that lubricates the joints so they don’t grind together. This helps you move smoothly and painlessly. But when your immune system turns against your synovium, the synovial fluid could thicken and swell, causing pain and stiffness in the joints. This is called synovial hypertrophy.

In normal joints, the synovium is about one to three cells thick. In someone with RA, however, the synovium is eight to 10 cells thick. If left untreated, this hypertrophied synovium—also called pannus—can invade and erode cartilage and bone, causing deformities in the joint. It can also weaken the muscles, ligaments, and tendons surrounding the joint.

“The goal of treating rheumatoid arthritis is to basically control inflammation,” says Saakshi Khattri, MD, a rheumatologist and assistant professor at the Department of Rheumatology, Icahn School of Medicine at Mount Sinai Hospital in New York City. “If you decrease inflammation, hopefully the joint destruction that is happening, or that might happen further down the line, is aborted.”

How JAK Inhibitors Help Control Inflammation

“When the immune system is revved up, you have all these cytokines, which are specialized protein molecules that are produced in the blood,” says Dr. Khattri. The Janus kinase (JAK) pathway acts like a switch in these cytokine-producing cells. This “switch” increases the inflammatory cytokines in the blood, which causes inflammation in the synovium.

JAK inhibitors are a type of disease-modifying antirheumatic drug (DMARD). A JAK inhibitor helps ease joint pain, swelling, and destruction by blocking the activity of the Janus kinase, which decreases inflammatory or proinflammatory molecules in the blood.

How to Know If Your Treatment Is Working

There are several ways to know if your JAK inhibitor, or other rheumatoid arthritis treatment, is working. The subjective way is simply assessing how you feel. “If a treatment is working, a patient will feel that the amount of morning stiffness they have is decreasing,” says Dr. Khattri. Here are some other ways to combat morning joint pain caused by RA.

Another way to learn if your RA treatment is working is to go to your doctor to test for inflammatory markers in the blood. “ESR (erythrocyte sedimentation rate) and CRP (c-reactive protein) are things that we can measure in blood, and we can compare the values post-treatment to what it was pre-treatment,” says Dr. Khattri.

“At the end of the day, it’s how a patient feels. Sometimes inflammatory molecules might not go down as expected, but how they feel overall is the more important question,” says Dr. Khattri.

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