Biologics and JAK Inhibitors: What’s the Difference?

Medically Reviewed by David Zelman, MD on February 12, 2024
3 min read

If you have rheumatoid arthritis, your doctor may prescribe a biologic or janus kinase (JAK) inhibitor. Both of these medicines dampen an overactive immune system, which is your body’s defense system against germs. They help block the inflammation that can cause swelling, pain, and joint damage.

Although biologics and JAK inhibitors treat the same issues, there are important differences between the two. Each works in its own way.


Both of these medications belong to a family of drugs called disease-modifying antirheumatic drugs (DMARDs). These medicines stop or slow down the disease process instead of only treating the symptoms. 

Biologics: These drugs are genetically engineered proteins that are made in a lab. Biologics zero in on specific parts of your immune system that drive inflammation. Most of the time, they block chemicals outside of cells called cytokines. These are proteins that help cells talk to each other. Some cytokines attach to the receptors on the surface of immune cells, causing changes that trigger inflammation.

There are four main categories of biologics:

  • Tumor necrosis factor inhibitors
  • B-cell inhibitors
  • Interleukin inhibitors
  • Selective co-stimulation modulators

Each one targets a certain cell or cytokine.

JAK inhibitors: JAK inhibitors stop inflammation from inside cells. These small molecules block enzymes called JAK1, JAK2, JAK3, and tyrosine kinase 2. When cytokines attach to cell receptors, JAK enzymes send messages within the cell. This sets off a series of signals that leads to inflammation. JAK inhibitors halt this process early on, like removing a domino in a chain.

JAK inhibitors prevent the action of many cytokines. Experts say there are more than 200 different cytokines, and about 60 of them use JAK enzymes.

Biologics and JAK inhibitors have different targets, and each works in its own way to fight inflammation.

Other differences include:

  • How you get them: You get biologics through a shot into your skin or an infusion in your bloodstream. You may need to go to your doctor’s office or give yourself a shot. It depends on what kind of biologic drug you’re on, but you’ll need treatment anywhere from daily to every few months. JAK inhibitors are taken as pills, usually once or twice a day.
  • When they became available: The first biologic drug for rheumatoid arthritis was approved in 1998. JAK inhibitors became available much later in 2012. This means that there’s more research on biologic drugs’ track record. Doctors often have a better idea of how safe they are and how well they work.

Although they have different actions, biologics and JAK inhibitors also have similarities.

  • Results: Biologics and JAK inhibitors can lower inflammation and protect against the rheumatoid arthritis joint damage. Both drugs can ease symptoms, such as pain, and improve quality of life. Studies suggest JAK inhibitors are just as effective as biologic drugs.
  • Side effects and risks: Early research suggests that biologic drugs and JAK inhibitors cause side effects at roughly the same rate. Because both suppress the immune system, they increase your risk of serious infections and certain cancers. JAK inhibitors may be safer because they aren’t linked to any allergies. Biologic drugs may cause an allergic reaction in a small number of people.

The first drug doctors prescribe for rheumatoid arthritis is usually methotrexate, a kind of DMARD. If methotrexate stops working or causes too many side effects, you’ll need to add or switch to a new drug. These include biologics and JAK inhibitors.

Most of the time, doctors prescribe biologics first. That's because more research has been done on these drugs. But roughly 30% of the time, biologic drugs aren’t enough. They may not help, or they may stop working. If that’s the case, your doctor may suggest JAK inhibitors.

Or you may decide on JAK inhibitors first. Many people prefer taking pills instead of getting a shot or IV. Talk to your doctor about your best option.