The Food and Drug Administration (FDA) has now approved tofacitinib (Xeljanz) to treat moderate-to-severe ulcerative colitis. Tofacitinib was approved for the treatment of rheumatoid arthritis in 2012 and psoriatic arthritis in 2017. Only the immediate-release form of tofacitinib is approved to treat ulcerative colitis, and it is administered orally twice a day. Coadministration is not recommended with biological therapies for ulcerative colitis (such as adalimumab [Humira], golimumab [Simponi], infliximab [Remicade], and vedolizumab [Entyvio]), or with potent immunosuppressants (such as azathioprine [Azasan, Imuran] and cyclosporine [Restasis and others]).

Ulcerative colitis is a chronic inflammatory disease in which the lining of the colon becomes inflamed and develops tiny ulcers that produce pus and mucus. These pathophysiological changes bring about symptoms of abdominal discomfort and frequent, often bloody diarrhea. Patients also experience weight loss, loss of appetite, and fatigue. Symptoms of ulcerative colitis flare and then go into remission. Ulcerative colitis is one of two irritable bowel diseases (the other is Crohn's disease).

Tofacitinib, a biologic, inhibits the enzyme Janus kinase, which plays a role in the cellular processes of hematopoiesis and immune cell function. Inhibition of this function leads to a decreased inflammatory response, as well as to decreased production of various blood cells.

Tofacitinib's efficacy was determined in three controlled clinical trials. The primary end point in two eight-week studies was achievement of remission within eight weeks of treatment, and a secondary end point was improved endoscopic appearance of the mucosa at the end of eight weeks of treatment. Patients who received tofacitinib achieved these end points at a statistically higher rate than those who received placebo. The primary end point in one long-term, 52-week trial was remission at week 52. Secondary end points were improved endoscopic appearance and sustaining corticosteroid-free remission at weeks 24 and 52. Again, those receiving tofacitinib were statistically more likely to achieve these end points than those receiving placebo.

The most common adverse effects of tofacitinib treatment were diarrhea, elevated cholesterol levels, headache, herpes zoster, increased blood creatine phosphokinase, nasopharyngitis, rash, and upper respiratory tract infections. For all indications, tofacitinib carries a black box warning citing the following serious, although rarer, adverse effects: risk of lymphoma and other malignancies and risk of serious infections (such as tuberculosis and various opportunistic infections) that may require hospitalization or be fatal. Larger doses of tofacitinib used to treat ulcerative colitis may put patients at greater risk for serious infections.

Prior to initiating therapy with tofacitinib, patients should be tested for latent tuberculosis. If positive, the tuberculosis should be treated prior to starting tofacitinib. Nurses should review the patient's laboratory work for absolute lymphocyte count, absolute neutrophil count, and hemoglobin levels prior to initiating therapy. Drug initiation should be postponed if the absolute lymphocyte count is less than 500 cells/mm3, the absolute neutrophil count is less than 1,000 cells/mm3, or hemoglobin levels are less than 9 g/dL. If patients develop a serious infection while taking tofacitinib, the drug should be discontinued until the infection is controlled. Because of tofacitinib's effect on the immune system, patients receiving the drug should not receive live virus vaccines (such as the measles-mumps-rubella or varicella vaccines), as this may result in the reduced effectiveness of the vaccine.

Nurses and NPs should confirm the tofacitinib dosage needed for an individual patient, as dose adjustments are needed for patients receiving cytochrome P-450 (CYP) isoenzyme CYP2C19 and/or CYP3A4 inhibitors; patients with moderate or severe renal impairment or moderate hepatic impairment; or patients with lymphopenia, neutropenia, or anemia. Nurses should provide patient education regarding the risk of developing serious infections while receiving tofacitinib. If a patient develops any symptoms of infection, they should contact the prescriber immediately.

For full prescribing information for tofacitinib, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf.