Update on the Use of JAK Inhibitors in Rheumatoid Arthritis Treatment

Research advances have led to a change in how doctors manage rheumatoid arthritis (RA). The European League Against Rheumatism (EULAR) is a group of RA experts that makes recommendations on how doctors should treat RA.1

Per EULAR’s suggestion, there is no longer a preference for biologic disease-modifying antirheumatic drugs (bDMARDs) if the first line of treatment fails.1 Adding a target-specific DMARD (disease-modifying antirheumatic drug), like a Janus kinase (JAK) inhibitor, is just as successful in treating RA.1

How do RA medications work?

RA damages the synovium, which is the tissue around the joints; this damage is due to chronic inflammation and swelling.2 The goal of RA drugs is to stop swelling. DMARDs are a type of medication used for RA treatment. Different DMARDs work to stop swelling in different ways.

What DMARDs are used for RA treatment?

The generic names of commonly used DMARDs are:1

  • Conventional synthetic DMARDS (csDMARDs) – methotrexate, leflunomide, sulfasalazine, hydroxychloroquine.
  • Targeted synthetic DMARDs (JAK inhibitors) – baricitinib, tofacitinib, upadacitinib.
  • Biologic DMARDs (bDMARDs) – adalimumab, certolizumab, etanercept, golimumab, infliximab, sarilumab, tocilizumab, abatacept, rituximab.

DMARDs can also be used with other drugs like steroids or non-steroidal anti-inflammatory drugs (NSAIDs).2 These drugs also stop swelling.

What is the treatment update for RA?

The first line of treatment for RA did not change.1 Doctors will still try methotrexate and steroids first and an extra csDMARD may be given. Doctors will monitor you for 3 to 6 months to see if the drugs are helping.1 They will look for the following signs and symptoms:1

  • High disease activity
  • Swollen joints
  • Bone erosions – a wound on the bones caused by inflammation
  • Markers in your blood – inflammatory markers or antibodies like rheumatoid factor (RF) and/or anticitrullinated protein antibody (ACPA) in the blood may mean your RA is worsening.

JAK inhibitors are just as good as biologic DMARDs

If doctors see any of these symptoms, EULAR suggests using JAK inhibitors or bDMARDs.1 The change in treatment is that doctors no longer prefer bDMARDs over JAK inhibitors. JAK inhibitors have proven to be just as good as bDMARDs in controlling RA.1

What is a JAK inhibitor?

JAK inhibitors are target-specific DMARDs. They go inside your cells looking for targets called enzymes.3 Enzymes help our cells carry out important processes. One of these processes is inflammation. The purpose of JAK inhibitors is to stop enzymes from causing inflammation.3

Success of JAK inhibitors for RA treatment

JAK inhibitors can help improve RA symptoms. People on JAK inhibitors also report less pain.3,4 Most people felt better within the first few weeks of treatment; using these drugs for several months led to the most improvement.3,4

What JAK inhibitors are currently approved for use?

Three JAK inhibitors are used for people with RA. They are:4-6

  • Tofacitinib (Xeljanz®) – taken as a pill. This drug was approved for use in 2012 by the U.S. Food and Drug Administration (FDA).
  • Baricitinib (Olumiant®) – taken as a pill. The FDA approved this drug in 2018.
  • Upadacitinib (Rinvoq®) – taken as a pill. Approved by the FDA in 2019.

Many other JAK inhibitors, like filgotinib and peficitinib, are being investigated in clinical trials.4

What are the active ingredients of JAK inhibitors?

The active ingredient in tofacitinib (Xeljanz®) is tofacitinib citrate. It is available in regular and extended-release pills.4

The active ingredient in baricitinib (Olumiant®) is baricitinib.5

The active ingredient in upadacitinib (Rinvoq®) is anhydrous upadacitinib. It is available as an extended-release pill.6

What are the side effects of JAK inhibitors?

The most common side effect is respiratory infection.6-8 Because JAK inhibitors change the way your immune system works, you may be at a higher risk of getting infections.3,4 If you are taking a JAK inhibitor and get an infection, call your doctor right away.

Tell your doctor if you have any history of heart disease. Some JAK inhibitors raise the risk of heart problems and certain cancers.8 A 2018 study noted that there may be a risk of blood clots due to taking JAK inhibitors.7 These drugs may also raise the amount of fat or cholesterol in your blood.6-8 Ask your doctor about all the side effects of JAK inhibitors.

Health considerations for JAK inhibitors

Your doctor may not prescribe a JAK inhibitor if you are pregnant. Having liver or kidney problems may also stop doctors from using JAK inhibitors to treat you.8 Underlying health problems may mean you cannot safely take JAK inhibitors. Tell your doctor before getting vaccinations while on JAK inhibitors.

Taking JAK inhibitors

JAK inhibitors may be helpful in treating your RA. Your doctor will work with you to find the right mix of drugs to try and put RA into remission. If you try 1 JAK inhibitor and show no improvement in 3 months, your doctor may switch you to another JAK inhibitor or bDMARD.1 Tell your doctor of any new symptoms or changes you have noticed while taking JAK inhibitors.


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