Last updated May 4, 2023, by Jose Lopes, PhD
Fact-checked by Patricia Silva, PhD
What is Xeljanz for ankylosing spondylitis?
Xeljanz (tofacitinib) is an oral treatment for adults with active ankylosing spondylitis (AS). Marketed by Pfizer, it was approved by the U.S. Food and Drug Administration to treat AS in December 2021 and is indicated for patients who’ve had an inadequate response or are intolerant to one or more TNF blockers (therapies that suppress the immune system).
Besides AS, the small-molecule therapy is also approved in the U.S. for treating certain adult patients with rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis, and also for a subset of patients ages 2 and older with polyarticular juvenile idiopathic arthritis.
How does Xeljanz work?
AS is a form of arthritis that mainly affects the spine and the joints between the spine and the pelvis. Inflammation of the areas where soft tissues (namely ligaments and tendons) attach to the vertebrae — the bones of the spine — is a hallmark symptom of AS and causes back pain and stiffness. Inflammation in a joint may be followed by growth of new bone and, as a result, vertebrae and joints may fuse.
Xeljanz is a Janus kinase (JAK) inhibitor intended to curtail an overactive immune system that, in AS and other conditions, leads to tissue damage. In cells, the JAK/STAT pathway is known to regulate the production of inflammatory mediators and has been associated with autoimmune diseases, conditions such as AS that are characterized by an attack of the immune system against the body’s own tissues.
Specifically, Xeljanz preferentially inhibits the JAK1 and JAK3 enzymes and, to a lesser extent, JAK2 and TYK2. It acts on immune T-cells, impairing the production of inflammatory T helper 17 cells while also suppressing the production of molecules implicated in inflammation through both innate and adaptive immune processes. Xeljanz was the first JAK inhibitor approved to treat active AS.
Who can take Xeljanz?
The U.S. Food and Drug Administration approved Xeljanz tablets and Xeljanx XR extended-release tablets in December 2021 for adults with active AS who have had an inadequate response or are intolerant to one or more TNF blockers. Such medications are a type of biological disease-modifying anti-rheumatic drug (DMARD) that reduce inflammation and fight disease progression by blocking the effects of a key inflammatory mediator called tumor necrosis factor (TNF).
Who should not use Xeljanz?
There are currently no contraindications for Xeljanz’s use. However, using it in combination with biologic DMARDs or potent immunosuppressants, including azathioprine and cyclosporine, is not recommended for AS patients.
The prescribing label for Xeljanz has a boxed warning for serious infections that lead to hospitalization or death, including tuberculosis. Treatment should be interrupted in the event of a serious infection until it is controlled. All patients should be monitored for active tuberculosis before and during Xeljanz treatment.
The boxed warning also indicates:
- A higher rate of mortality from any cause with Xeljanz compared to TNF blockers, as seen in rheumatoid arthritis patients receiving the therapy.
- More frequent lymphomas (a cancer type that begins in cells of the lymphatic system) and lung cancers in rheumatoid arthritis patients on Xeljanz than in those on TNF blockers. Other types of cancer have also been observed. The risks and benefits of starting treatment should be considered in patients with a known cancer, those who develop cancer while taking Xeljanz, and those who are current or past smokers.
- A higher rate of MACE — major adverse cardiovascular events, defined as cardiovascular death, nonfatal myocardial infarction (heart attack), and stroke — seen with Xeljanz than with TNF blockers in people with rheumatoid arthritis. The benefits and risks of starting and staying on Xeljanz therapy should be considered in patients who are current or past smokers and those with other cardiovascular risk factors.
- Cases of thrombosis, when blood clots block veins or arteries, have been reported in people taking Xeljanz. Patients at increased risk or with symptoms of thrombosis should not receive the therapy.
How is Xeljanz administered?
Xeljanz is an oral medication AS patients may take as 5 mg tablets or as 11 mg extended-release tablets (known as Xeljanz XR).
Xeljanz as a regular 5 mg tablet is taken twice a day and is immediately released into the bloodstream over several hours. Tablets are round, white, and film-coated. They are marked “Pfizer” on one side and “JKI 5” on the other side.
Xeljanz XR is taken once a day and is released into the bloodstream throughout the day. Tablets are oval, pink, and film-coated. They are marked “JKI 11” on one side of the tablet.
Both forms may be taken with or without food. Xeljanz XR should be swallowed whole and is not to be crushed, split, or chewed. People taking Xeljanz XR may see the empty shell from the tablet in their stool after the therapy has been absorbed by the body.
Patients with moderate to severe kidney impairment or moderate liver impairment are recommended to take 5 mg once daily of either the immediate-release or the extended-release formulations. Those taking Xeljanz should also reduce their dose to 5 mg once daily if on strong CYP3A4 inhibitors, such as the antifungal medicine ketoconazole, or a moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor such as fluconazole, also an antifungal therapy.
Xeljanz in clinical trials
The approval of Xeljanz for AS is based on results from a Phase 3 clinical trial (NCT03502616) that enrolled 269 adults with the disease who had an inadequate response to at least two NSAIDs.
The study had a 16-week double-blind period wherein patients received Xeljanz 5 mg twice daily or a placebo and a 32-week open-label period in which all participants received Xeljanz.
Results of the Phase 3 study showed patients on Xeljanz achieved greater improvements relative to those on a placebo at week 16. This was assessed by both the ASAS20 and the ASAS40 tools, which have four domains: pain, function, inflammation, and a patient global assessment. ASAS20 reflects an improvement of at least 20%; ASAS40 reflects an improvement of at least 40%.
Also, the improvements in the ASAS domains, in other measures of disease activity, and in the Ankylosing Spondylitis Quality of Life (a questionnaire about restrictions in daily activities, pain, fatigue, and emotional state) were also greater with Xeljanz.
Overall, the safety profile of Xeljanz in AS patients was consistent with the safety profile seen in patients with rheumatoid arthritis and psoriatic arthritis.
Common side effects of Xeljanz
The most common side effects associated with Xeljanz in people with AS include:
- upper respiratory tract infection
- nasopharyngitis (common cold)
- diarrhea
- headache.
Serious infections
Xeljanz or Xeljanz XR should not be used during an active serious infection, including localized infections. Patients with chronic or recurrent infections, who have had tuberculosis or a serious or opportunistic infection, who have been to or lived in areas where tuberculosis or fungal infections are particularly present, or who have underlying conditions that may make them at risk of infections, should carefully consider the risks and benefits of Xeljanz treatment..
Monitoring signs and symptoms of infection during Xeljanz therapy is recommended. Low levels of white blood cells may increase the risk of infections.
Gastrointestinal perforations
People at increased risk of gastrointestinal perforations (holes in the digestive tract) should use Xeljanz with caution. This includes, for example, people taking NSAIDs and those with a history of diverticulitis (small bulges in the lining of the intestine). Patients with new abdominal symptoms should be immediately evaluated so gastrointestinal perforation can be identified early.
Laboratory monitoring
Xeljanz or Xeljanx XR may be associated with changes in levels of immune cells called lymphocytes and neutrophils, as well as hemoglobin (the protein in red blood cells that carries oxygen throughout the body), liver enzymes and lipids (fatty molecules). As such, levels of these cells, proteins, and molecules should be monitored before and regularly during treatment, and people with low levels of lymphocytes, neutrophils, and hemoglobin, or high levels of liver enzymes should not initiate treatment with Xeljanz or treatment should be interrupted in those who already started it.
Immunizations
Live vaccines should not be used at the same time as Xeljanz or Xeljanz XR therapy. The time between taking a live vaccine and starting treatment should be in accordance with vaccination guidelines regarding immunosuppressants.
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