What You Need to Know About Xeljanz

An Oral JAK Inhibitor Approved to Treat Ulcerative Colitis

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Xeljanz (tofacitinib) is a drug manufactured by Pfizer, Inc. and is the first entry into in a class of medications called Janus kinase (JAK) inhibitors. Xeljanz was approved to treat rheumatoid arthritis in November 2012, psoriatic arthritis in December 2017, and to treat adults with moderately to severely active ulcerative colitis in June 2018.

This drug is an oral medication that comes in a tablet form.

For ulcerative colitis, Xeljanz is given twice a day in either a 5 mg or a 10 mg dose. Xeljanz may be given by itself (called monotherapy) or at the same time as other therapies for ulcerative colitis that do not suppress the immune system. There is an extended release version of this medication that is approved for use in rheumatoid arthritis but not for ulcerative colitis.

How Xeljanz Works

JAKs are intracellular enzymes that are found in many cells in the body, including in the bones and the joints. They transmit signals that play a role in activating the body's immune response. Xeljanz inhibits JAK-1 and JAK-3, which in turn block several types of interleukins that are responsible for activating T cells and B cells. 

It’s thought that by suppressing JAKs, and thereby inhibiting the chain of events that activates T and B cells, it may stop the inflammatory process that fuels some immune-mediated conditions, such as arthritis and inflammatory bowel disease (IBD).

Dosage

Xeljanz may be given for ulcerative colitis in a 10 mg dose twice a day for eight weeks, in what’s called the induction phase. After eight weeks, the 10 mg twice a day may be continued, or it may be changed to a 5 mg dose twice a day. Xeljanz may be taken with or without food.

It is not recommended that Xeljanz be given at the same time as immune-suppressing medications or those that are in the drug class called biologics.

Immunosuppressive medications given for ulcerative colitis may include Imuran (azathioprine) and cyclosporine. Biologics approved to treat ulcerative colitis include Entyvio (vedolizumab)Humira (adalimumab)Remicade (infliximab), and Simponi (golimumab).

Financial Assistance

There is no generic form of Xeljanz available. There is, however, financial support available from Pfizer, the manufacturer of Xeljanz, for some patients. Learn more about this program by calling 1-844-XELJANZ (1-844-935-5269) or through their website at https://uc.xeljanz.com/financial-support

Side Effects and Special Concerns

According to Xeljanz prescribing information, care should be taken when prescribing this medication to anyone who: 

  • Currently has a serious infection
  • Is at risk for perforation of the intestines
  • Has a low neutrophil or lymphocyte (types of white blood cells) count
  • Has a low hemoglobin level (less than 9 g/dL)

From the results of clinical trials in ulcerative colitis patients receiving 10 mg of Xeljanz twice a day, the most common side effects and the percentage of patients in which they occurred included:

  • Anemia (2 percent)
  • Common cold (nasopharyngitis) (14 percent)
  • Diarrhea (5 percent)
  • Gastroenteritis (infectious diarrhea) (4 percent)
  • Increased cholesterol levels (9 percent)
  • Headache (3 percent)
  • Herpes zoster (5 percent)
  • High blood pressure (2 percent)
  • Increased blood creatine phosphokinase (7 percent)
  • Nausea (4 percent)
  • Rash (6 percent)
  • Upper respiratory tract infection (6 percent)

Interactions

Medication interactions could cause the level of Xeljanz to be increased or decreased in the body, potentially altering its effectiveness. In the case of immune-suppressing drugs, the risk is that the immune system could be dampened too much, placing a patient at risk for infection. Xeljanz may interact with:

  • Ketoconazole (could increase Xeljanz dose in the body)
  • Fluconazole (could increase Xeljanz dose in the body)
  • Rifadin (rifampin) (could decrease Xeljanz dose in the body)
  • Immunosuppressive drugs such as Imuran, tacrolimus, and cyclosporine (could increase immune suppression)
  • Anti-TNF medications such as Remicade (could increase immune suppression)

During Pregnancy

Xeljanz is Pregnancy Category C drug, which means that it has not been studied extensively and the benefits expected for taking this drug during pregnancy should outweigh the potential risk. It is recommended that women who are breastfeeding not receive Xeljanz because there are no studies to understand if a nursing baby might be affected by the medication.

A small number of women have become pregnant while taking Xeljanz, and while there is no formal study done yet, there is information on how their pregnancies proceeded. There was not an increase in birth defects or in pregnancy loss in these women. Until more data is available, however, the recommendation is for women to avoid becoming pregnant while receiving Xeljanz.

There are no studies in men to determine if there is an effect on pregnancy, but in the small number of fathers who were receiving Xeljanz at the time of conception, there was not an increase in pregnancy loss or birth defects.

Warnings and Precautions

As with any medication for IBD, a gastroenterologist is going to be the best source for advice and understanding about personal risks when taking this drug because not every person has the same level of risk for adverse events. In the clinical trials for ulcerative colitis, some of the potential side effects were shown to occur more often with the 10 mg twice a day dosage versus the 5 mg twice a day dosage.

The medication guide for Xeljanz has a boxed warning regarding a risk of serious infections. In the eight week trials for patients with ulcerative colitis, there were more infections among those receiving the drug than those receiving the placebo.

In the 52 week trial, there were more infections, including shingles (herpes zoster), in the Xeljanz group than in the placebo group. Those considering Xeljanz to treat ulcerative colitis should speak with their gastroenterologist regarding the personal risk of these types of infections, in order to put it into the correct perspective. 

Prior to starting therapy with Xeljanz, people with ulcerative colitis should be tested for tuberculosis. There should also be regular monitoring for tuberculosis infection, even if the test came back negative for it. 

Xeljanz was associated with an increase in cholesterol levels in the trials for ulcerative colitis, although to a lesser degree than in trials for arthritis. It’s important to discuss this potential adverse effect with a gastroenterologist in order to better understand if cardiovascular health is an important consideration when taking this medication.

There was an increase in cases of non-melanoma skin cancer among those taking Xeljanz versus those receiving placebo in clinical trials. This has not been well-studied and so it’s unclear how much of the risk is from the underlying ulcerative colitis versus from the medication. All people with ulcerative colitis should be regularly monitored for skin cancer and should take precautions against too much sun exposure.

Effectiveness

Xeljanz was studied in three phase 3, randomized, double-blind, placebo-controlled trials in people with ulcerative colitis (OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain). The goal of the trials was to determine what percentage of those enrolled in the trial would experience remission from the ulcerative colitis. Whether or not remission occurred was decided through the use of the Mayo Score.

The Mayo score is a clinical tool used to quantify ulcerative colitis disease activity, and it measures the number of bowel movements a day, if there is bleeding, if there is mucus, and if the physician would say that the disease mild, moderate, or severe after an endoscopy procedure. The scale goes from 0 to 12, and for these trials, the score that would define remission is a 2 or lower.

OCTAVE Induction 1
There were 598 patients with ulcerative colitis enrolled in this trial. In this group of patients, previous medications that were tried to control the ulcerative colitis included coritcosteroids, Imuran (azathioprine), 6 mercaptopurine (6 MP), or an anti-tumor necrosis factor (TNF) biologic medication.

After 8 weeks, 18.5 percent of the patients with ulcerative colitis receiving Xeljanz, 10 mg twice a day, achieved remission, in comparison to a remission rate of 8.2 percent in those who received the placebo. In regards to deeper, mucosal healing, this effect was shown in 31 percent of patients receiving Xeljanz versus 16 percent receiving the placebo.

OCTAVE Induction 2
This trial included 541 patients with ulcerative colitis whose disease did not respond to other medical therapies or to an anti-TNF medication. Enrollees received either 10 mg of Xeljanz twice a day or a placebo for eight weeks.

There were 16.6 percent in the Xeljanz group that experienced remission from ulcerative colitis, versus 3.6 percent in the placebo group. In this trial, 31 percent of the participants receiving Xeljanz and 16 percent of those receiving placebo achieved mucosal healing. 

OCTAVE Sustain
There were 593 people with ulcerative colitis included in this trial. These enrollees had already responded to Xeljanz in the induction phase (eight weeks of the drug at 10 mg twice a day). At this point they were randomized to continue the drug at the 10 mg twice a day, change to 5 mg twice a day, or receive a placebo.

This trial continued for 52 weeks, to determine how patients fared on the different doses of Xeljanz or the placebo. Of those receiving 10 mg of the drug twice a day, 40.6 percent were in remission, versus 34.3 percent in the 5 mg twice a day group, and 11.1 percent in the placebo group. 

A Word From Verywell

A new class of medications for treating IBD is an important development for people who live with these diseases. It’s important to remember, however, that only a physician can help people with IBD understand which treatments will be appropriate and put the risk of adverse effects into perspective. The future of the treatment pipeline for IBD is strong and there’s hope that this new class of drugs will continue to improve and help more people with IBD achieve remission from the disease. 

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