How Xeljanz Works

One way that cells in the body communicate with each other is with special signalling proteins called cytokines. Cytokines are made and released by cells and drift around and until they encounter another cell and bind to a receptor on its surface. When a cytokine binds to the surface of a cell, it passes its message to the cell’s nucleus (its “brain” or command centre) using a process called signal transduction. The nucleus responds to a signal by producing the appropriate protein or peptide that’s coded for in its DNA (this is called activation of transcription).

One of the important signal transduction pathways in the body uses an enzyme called Janus Kinase (JAK) and another molecule called Signal Transducer and Activation of Transcription (STAT) to send a signal to a cell’s nucleus. The JAK-STAT pathway is important for sending signals related to bone marrow and immune system activation.

Xeljanz is a newer small molecule that enters a cell and binds to the ATP binding site on the enzyme Janus Kinase (JAK). In doing this, it prevents JAK from activating STAT which would then complete the process of sending its signal to the cell’s nucleus.

In rheumatoid arthritis and many other autoimmune disorders, the immune system is not functioning correctly. It attacks the joints the same way it attacks disease-causing germs. By disrupting a key signal sending process related to immune system activation, Xeljanz interferes with the ability of immune system cells to talk with each other. When these cells can’t communicate as effectively, they have a hard time coordinating their attack on the joints. The end result is improvement in the symptoms of a patient’s arthritis.

Side Effects of Xeljanz

The most common side effects of Xeljanz include include upper respiratory tract infections (common cold, sinus infections) and related symptoms. It might also cause headaches or diarrhea. Patients should tell their doctor if these effects are troublesome.

LESS SERIOUS side-effects include:

  • Nausea, indigestion, and diarrhea
  • Headaches
  • Upper respiratory tract infection (nasopharyngitis)
  • Cholesterol Levels – Xeljanz may increase cholesterol levels. This will be monitored through blood tests

MORE SERIOUS side-effects include:

  • Infection – There have been serious and rare infections associated with the use of Xeljanz. Any infections or fevers should be taken very seriously and reviewed by a doctor
  • Blood Counts – Xeljanz can cause changes in the numbers of white blood cells (which are needed to fight infection) and red blood cells (which carry oxygen)
  • Liver – Xeljanz may irritate the liver. This does not usually cause symptoms but may be found on blood tests. It is uncommon and usually reversible when regularly monitored with your monthly blood tests
  • Bowels – Xeljanz may increase the risk of bowel perforation. This is very rare.
  • Kidneys – Xeljanz may cause a slight decrease in kidney function in some people (increased creatinine). This is monitored through regular blood tests.
  • Blood Clots – Xeljanz may increase the risk of blood clots in the legs (deep venous thrombosis or DVT) or in the lungs (pulmonary embolism or PE). Any new leg swelling or shortness of breath should be taken seriously and reviewed by a doctor.
  • Shingles – Xeljanz may increase your risk of developing shingles. Please talk to your doctor about the shingles vaccine.

How to minimize the side-effects of Xeljanz:

  • Patients should take the medicine twice a day, as prescribed by their doctor
  • Patients should get regular blood tests as requested by their doctor to monitor for side effects, and remember to attend their appointments

Who Should NOT Take Xeljanz

Patients should contact their doctor before intentionally missing a dose of Xeljanz. However, in the following situations, it would be advisable to stop taking the medicine and call a doctor:

  • Fever
  • An infection or signs of an infection
  • Pregnancy

Patients who are about to have surgery should discuss stopping Xeljanz with their doctor.

Some medications may not be safe to take with Xeljanz including ketoconazole, fluconazole, and rifampin. Patients should always discuss all of the medications that they are taking with their doctor.

Some medications may increase the risk of infection and should not be taken with Xeljanz, including biologics and other potent immunosuppressive medications such as cyclosporine or azathioprine.

When to Call a Doctor

Patients taking Xeljanz should call their doctor if they feel sick and want to stop, or if they are concerned about any side effects.

Other reasons to call a doctor while taking Xeljanz include:

  • Developing a fever or suspected infection
  • Planning for surgery
  • Becoming pregnant or planning on pregnancy
  • Planning on getting any vaccinations
  • New leg swelling or shortness of breath
  • Severe abdominal pain