What are the considerations and guidelines for using Xeljanz (tofacitinib) in treating rheumatoid arthritis and ulcerative colitis?

From the Guidelines

Xeljanz (tofacitinib) should be considered for the treatment of moderate to severe rheumatoid arthritis and ulcerative colitis, but only after careful patient selection and monitoring due to its safety profile, as recommended by the most recent guidelines 1.

Key Considerations

• The typical dosage for rheumatoid arthritis is 5 mg twice daily, while ulcerative colitis treatment usually begins with 10 mg twice daily for induction (8 weeks), followed by 5 mg twice daily for maintenance.
• Before starting Xeljanz, patients should undergo tuberculosis screening, hepatitis B/C testing, complete blood count, and lipid panel, as suggested by previous studies 1.
• The medication is contraindicated in patients with serious infections, severe liver disease, or absolute lymphocyte count below 500 cells/mm³, and should be used cautiously in patients at high risk of major adverse cardiovascular events, as highlighted in the latest guidelines 1.

Monitoring and Safety

• Regular monitoring is essential, including blood counts every 1-3 months and lipid testing 4-8 weeks after initiation, to minimize the risk of serious side effects.
• Patients should be aware of potential serious side effects including increased risk of serious infections, malignancy, gastrointestinal perforations, and thrombosis (particularly at higher doses), as reported in recent studies 1.

Mechanism of Action

• Xeljanz works by inhibiting Janus kinase enzymes, disrupting the signaling pathway that contributes to inflammation in these autoimmune conditions, as explained in previous research 1.

Special Considerations

• The medication should be temporarily discontinued during serious infections and for surgical procedures, and dose adjustments may be necessary for patients with renal or hepatic impairment, as recommended by the guidelines 1.
• In women of childbearing age actively contemplating pregnancy, it is recommended to avoid JAK inhibitors and S1P receptor modulators and select an alternate therapeutic option when possible, due to the lack of data on their safety during pregnancy 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Administration Instructions • XELJANZ XR (tofacitinib extended-release tablets) is not interchangeable or substitutable with XELJANZ Oral Solution. (2.1) • Changes between XELJANZ and XELJANZ XR should be made by the healthcare provider. (2. 1) • Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm3, an absolute neutrophil count (ANC) <1000 cells/mm3 or hemoglobin <9 g/dL. (2.1) Recommended Dosage Rheumatoid Arthritis • XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. (2. 2) • Recommended dosage in patients with moderate and severe renal impairment or moderate hepatic impairment is XELJANZ 5 mg once daily. (2,8.7,8.8) Ulcerative Colitis • Induction: XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks; evaluate patients and transition to maintenance therapy depending on therapeutic response. If needed, continue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for a maximum of 16 weeks Discontinue XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily after 16 weeks if adequate therapeutic response is not achieved. (2. 3) • Maintenance: XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily. For patients with loss of response during maintenance treatment, XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily may be considered and limited to the shortest duration, with careful consideration of the benefits and risks for the individual patient. Use the lowest effective dose needed to maintain response. (2. 3)

The considerations and guidelines for using Xeljanz (tofacitinib) in treating rheumatoid arthritis and ulcerative colitis are as follows:

• Rheumatoid Arthritis: The recommended dosage is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
• Ulcerative Colitis:
  • Induction: The recommended dosage is XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily for 8 weeks.
  • Maintenance: The recommended dosage is XELJANZ 5 mg twice daily or XELJANZ XR 11 mg once daily.
• Dosage adjustment is needed in patients with moderate and severe renal impairment or moderate hepatic impairment.
• Contraindications: Do not initiate XELJANZ/XELJANZ XR/XELJANZ Oral Solution if absolute lymphocyte count <500 cells/mm3, an absolute neutrophil count (ANC) <1000 cells/mm3, or hemoglobin <9 g/dL 2.

From the Research

Considerations for Using Xeljanz (Tofacitinib) in Treating Rheumatoid Arthritis

• Xeljanz (tofacitinib) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3, and is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs 3.
• Tofacitinib monotherapy and combination therapy with a conventional synthetic DMARD (csDMARD) have been shown to be effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL) in patients with RA 3, 4.
• The tolerability profile of tofacitinib is generally similar to that of biological DMARDs (bDMARDs), with infections and infestations being the most common adverse events (AEs) in tofacitinib recipients 3.
• The incidence of herpes zoster (HZ) is higher with tofacitinib than in the general RA population, although infections are clinically manageable 3.

Considerations for Using Xeljanz (Tofacitinib) in Treating Ulcerative Colitis

• Tofacitinib is approved for the treatment of moderately to severely active ulcerative colitis (UC) and has been shown to be effective in reducing symptoms and improving quality of life in patients with UC 5, 6.
• Tofacitinib may be an effective induction strategy in biologic-experienced patients hospitalized with acute severe ulcerative colitis (ASUC) 6.
• A systematic review of tofacitinib for ASUC found that it appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients who are otherwise deemed to require colectomy 7.
• However, large high-quality studies are needed to confirm the efficacy and safety of tofacitinib in treating UC and ASUC 6, 7.

Guidelines for Using Xeljanz (Tofacitinib)

• Tofacitinib should be used in accordance with the approved labeling and prescribing information, and under the guidance of a healthcare professional 3, 4.
• Patients should be closely monitored for adverse events, including infections and infestations, and herpes zoster 3.
• The dose and duration of tofacitinib treatment should be individualized based on the patient's response and tolerability 6.