Xeljanz Approved for Rheumatoid Arthritis in European Union

March 28, 2017

The European Commission has approved marketing authorization for tofacitinib citrate (Xeljanz, Pfizer, Inc) for adult patients with moderate-to-severe rheumatoid arthritis (RA), according to a company news release.

The Committee for Medicinal Products for Human Use of the European Medicines Agency recommended granting marketing authorization for this indication on January 27, 2017. The US Food and Drug Administration approved tofacitinib citrate for RA on November 6, 2012, and approved an extended-release form of the medication for patients with RA on February 24, 2016. With this approval, tofacitinib is now approved in more than 80 countries globally.

The approval is for tofacitinib citrate 5 mg by mouth twice daily in combination with methotrexate (MTX) for patients with moderate-to-severe RA who have responded inadequately to, or who are intolerant to, at least one disease-modifying antirheumatic drug (DMARD). It can be used as monotherapy in patients who are intolerant to MTX or in whom treatment with MTX is inappropriate.

"With the approval of tofacitinib, rheumatologists and patients in the [European Union] now have an additional treatment option for the management of rheumatoid arthritis that can be taken with or without methotrexate," Ronald van Vollenhoven, professor of rheumatology and director of the Amsterdam Rheumatology and Immunology Center ARC, explained in the news release. "This is an important advancement for the rheumatology community as up to one-third of people with rheumatoid arthritis may not achieve a response with current treatments and a number of patients may not sustain a response."

Tofacitinib is a Janus kinase inhibitor that acts inside the cell to disrupt a signaling pathway involved with the inflammation characteristic of moderate-to-severe active RA. Several RA treatment recommendations, including those published by the European League Against Rheumatism, the American College of Rheumatology, and the Asia Pacific League of Associations for Rheumatology, include treatment with tofacitinib.

The decision follows consideration of a submission package that included data from the Phase 3 Oral Rheumatoid Arthritis triaLs (ORAL) global development program, as well as real-world data. The clinical trial program was conducted in a diverse population of patients with RA. Results demonstrated tofacitinib was effective and safe when used both with and without MTX in the treatment of moderate-to-severe disease.

To date, tofacitinib's development program includes more than 8 years of safety data from the long-term extension studies representing more than 21,000 patient-years of exposure to the drug.

Frequently seen adverse effects include upper respiratory tract infections, headache, diarrhea, nasal congestion, sore throat, and nasopharyngitis.


Use of tofacitinib in combination with biologic DMARDs or potent immunosuppressants, such as azathioprine and cyclosporine, is not recommended. The safety and efficacy of tofacitinib in patients with hepatitis B or C have not been established, and the drug is not intended for those with severe liver problems. Safety and efficacy in children have not been established.

Tofacitinib can decrease the immune system's ability to fight infections. Some patients can develop serious or fatal infections while taking tofacitinib, including tuberculosis and infections caused by bacteria, fungi, or viruses that can invade the entire body. Patients should undergo tuberculosis testing before beginning treatment with tofacitinib and be monitored closely for signs and symptoms of tuberculosis and other infections during treatment. Patients should not begin taking tofacitinib if they have any kind of infection unless instructed by their healthcare provider.

Patients may have a higher risk for shingles.

Because tofacitinib changes the way the immune system functions, tofacitinib may increase the risk for certain cancers, and patients who take it may develop lymphoma and other cancers, including skin cancers.

Live vaccines should not be used concurrently with tofacitinib, and patients should update their immunizations according to current immunization guidelines before beginning treatment.

Some patients who have taken tofacitinib concurrently with other medications to prevent kidney transplant rejection have developed Epstein Barr virus-associated post-transplant lymphoproliferative disorder.

Some patients using tofacitinib may develop gastrointestinal perforations, particularly those who also take nonsteroidal anti-inflammatory drugs, corticosteroids, or methotrexate. Tofacitinib should be used cautiously in patients with increased risk for gastrointestinal perforation, and patients should inform their healthcare provider immediately if they have fever and continued stomach-area pain or changed bowel habits.

Tofacitinib may affect certain lab tests including low blood cell counts, increases in certain liver tests, and increases in cholesterol levels. Healthcare providers should perform these blood tests before and during treatment, and may discontinue tofacitinib because of changes in blood cell counts or liver test results.

The safety of tofacitinib when used during pregnancy has not been established, and it should not be used by women who are breastfeeding.

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