The FDA ( Food and Drug Administration ) has approved Xeljanz ( Tofacitinib citrate ) 5 mg twice daily for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to Methotrexate.
Xeljanz may be used as monotherapy or in combination with Methotrexate or other non-biologic disease-modifying antirheumatic drugs ( DMARDs ). Xeljanz should not be used in combination with biologic DMARDs or with potent immunosuppressives, such as Azathioprine and Cyclosporine.

Xeljanz is the first approved rheumatoid arthritis treatment in a new class of medicines known as Janus kinase ( JAK ) inhibitors and the first new oral DMARD for RA in more than 10 years.
Xeljanz is approved as a second-line medicine for RA, which means treatment with a biologic is not required before taking Xeljanz.

Xeljanz is specifically designed to inhibit the JAK pathways, which are signaling pathways inside the cell that play an important role in the inflammation involved in RA. With one of the largest clinical databases of any RA drug ever submitted to the FDA for review, the comprehensive, multi-study, global clinical development program evaluated approximately 5,000 patients who represent a broad cross-section of the RA patient population.

Safety findings observed in the overall Xeljanz RA program include serious and other important infections, including tuberculosis and herpes zoster; malignancies, including lymphoma; gastrointestinal perforations; decreased neutrophil and lymphocyte counts; decreased hemoglobin; liver enzyme elevations; and lipid elevations.

The most common serious adverse events were serious infections. The most commonly reported adverse events were upper respiratory tract infections, headache, diarrhea and nasopharyngitis.

In the clinical trials, Xeljanz was studied in both a 5 mg and 10 mg twice-daily dosing regimen. The FDA has approved the 5 mg twice-daily dose in the second-line setting and has indicated that further data are required to assess the benefit: risk profile of the 10 mg twice-daily dose.

FDA has approved Xeljanz with a Risk Evaluation and Mitigation Strategy ( REMS ) designed to inform healthcare providers and patients about the serious risks associated with Tofacitinib treatment. The approved REMS includes a Medication Guide for patients, a communication plan for healthcare providers and pharmacists, and periodic submissions of assessments of the REMS.
Pfizer has agreed to conduct post-marketing clinical trials to evaluate the long-term safety of Tofacitinib and to assess Tofacitinib in the pediatric population with polyarticular juvenile idiopathic arthritis.

Important safety information

Tofacitinib can lower the ability of the immune system to fight infections. Some people have serious infections while taking Tofacitinib, including tuberculosis, and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Healthcare providers should test patients for tuberculosis before starting Tofacitinib, and monitor them closely for signs and symptoms of tuberculosis and other infections during treatment.

Tofacitinib may increase the risk of certain cancers by changing the way the immune system works. Lymphoma and other cancer can happen in patients taking Xeljanz.

Some people taking Tofacitinib get tears in their stomach or intestines. Patients should tell their healthcare provider right away if they have fever and stomach-area pain that does not go away or a change in bowel habits.

Tofacitinib can cause changes in certain lab test results including low blood cell counts, increases in certain liver tests and increases in cholesterol levels. Normal cholesterol levels are important to good heart health. Healthcare providers may stop Xeljanz treatment because of changes in blood cell counts or liver test results.

Patients should tell their healthcare providers if they plan to become pregnant or are pregnant.

It is not known if Tofacitinib will harm an unborn baby. To monitor the outcomes of pregnant women exposed to Tofacitinib, a pregnancy registry has been established.

Patients should tell their healthcare providers if they plan to breastfeed or are breastfeeding. Patients and their healthcare provider should decide if they will take Tofacitinib or breastfeed. They should not do both.

In carriers of the hepatitis B or C virus ( viruses that affect the liver ), the virus may become active while using Tofacitinib. Healthcare providers may do blood tests for hepatitis before and during treatment with Xaljanz.

Common side effects include upper respiratory tract infections ( common cold, sinus infections ), headache, diarrhea, nasal congestion, sore throat, and runny nose ( nasopharyngitis ).

Source: Pfizer, 2012

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