The US Food and Drug Administration (FDA) has approved Pfizer's Xeljanz (tofacitinib citrate) 5 mg twice daily for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) 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 potent immunosuppressives, such as azathioprine and cyclosporine.

Xeljanz (ZEL'jans) is the first approved RA 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 an important new option that could potentially change the way rheumatologists treat this serious autoimmune disease,” said Ian Read, chairman and chief executive officer of Pfizer. “With its novel mechanism of action, the discovery and development of Xeljanz by Pfizer scientists reflects our commitment to R&D innovation and our dedication to bringing important and meaningful medicines to patients.”

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.

“RA is a serious and disabling disease that affects people in their everyday lives, and many patients do not adequately respond or are intolerant to currently available therapies,” said study investigator Stanley Cohen, MD, clinical professor of rheumatology at the University of Texas Southwestern Medical School; co-director, Division of Rheumatology, Presbyterian Hospital Dallas; and co-medical director, Metroplex Clinical Research Center. “In clinical trials, Xeljanz significantly reduced the signs and symptoms of RA and improved physical function. As a physician, I am pleased that we have another choice for patients living with inadequately controlled, moderately to severely active RA.”

“In clinical trials, Xeljanz demonstrated consistent efficacy across a broad range of clinical measures and patient types, including patients who inadequately responded to non-biologic DMARDs and anti-TNF agents, and it has a safety profile that is well-characterized to date,” said Geno Germano, president and general manager, Specialty Care and Oncology, Pfizer. “We are proud of the comprehensive data that support the use of Xeljanz, and we are excited to make it available to patients in the U.S. as a powerful oral option that can be taken as a second-line treatment with or without methotrexate.”

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, diarrhoea and nasopharyngitis.

Regarding the potential for further assessment by the FDA of the inhibition of structural damage, Pfizer plans to immediately discuss with the FDA the submission of the results of the previously disclosed ORAL Start (A3921069) study, which demonstrated significant efficacy of Xeljanz taken as monotherapy versus methotrexate, including inhibiting structural damage. The ORAL Start study was ongoing at the time of the New Drug Application submission and was not included in the original application to the FDA.

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. Pfizer will continue to generate additional clinical data on the 10 mg twice-daily dose and work with the FDA to understand the additional data needed for further assessment 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 Xeljanz 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 evaulate that long-term safety of Xeljanz and to assess Xeljanz in the paediatric population with polyarticular juvenile ideopathic arthritis (JIA).

Xeljanz is a prescription medicine called a Janus kinase (JAK) selective inhibitor. Xeljanz is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well.