Xeljanz(tofacitinib)

Xeljanz (tofacitinib) received initial U.S. approval in 2012. It is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate, and may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). Xeljanz is also indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other DMARDs. A supplemental New Drug Application (sNDA) for Ulcerative Colitis was approved on May 30, 2018, for the treatment of adult patients with moderately to severely active ulcerative colitis (UC).

Recommended dosages vary by indication and patient condition. For Rheumatoid Arthritis and Psoriatic Arthritis, the recommended dosage is 5 mg twice daily (XELJANZ) or 11 mg once daily (XELJANZ XR). For Ulcerative Colitis, the induction dosage is 10 mg twice daily, with maintenance at 5 or 10 mg twice daily. Dosage adjustments are recommended for patients with moderate/severe renal impairment or moderate hepatic impairment, or those receiving strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors with strong CYP2C19 inhibitors. XELJANZ/XELJANZ XR is not recommended for patients with severe hepatic impairment. Discontinuation of the 10 mg twice daily dosage for Ulcerative Colitis is advised after 16 weeks if no adequate therapeutic benefit is observed. In a study, 18% of patients were in remission at week 8.

Safety considerations include not initiating XELJANZ/XELJANZ XR in patients with an absolute lymphocyte count <500 cells/mm3, absolute neutrophil count (ANC) <1000 cells/mm3, or hemoglobin <9 g/dL. Dosing should be interrupted for patients with ANC 500 to 1000 cells/mm3. The most common adverse reactions in Rheumatoid and Psoriatic Arthritis (first 3 months, >2%) were upper respiratory tract infection, nasopharyngitis, diarrhea, and headache. A postmarketing study (3400-3) on malignancy risk has an interim report date of 01/2023 and a final report submission date of 06/2026.