What is the role of XELJANZ (tofacitinib) in the treatment of Rheumatoid Arthritis (RA)?

From the Guidelines

Xeljanz (tofacitinib) is a recommended treatment option for rheumatoid arthritis (RA) patients who have not responded adequately to methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.

Key Points

• The standard dosing of Xeljanz is 5 mg twice daily or 11 mg extended-release once daily.
• Xeljanz belongs to a class of medications called JAK inhibitors, which work by blocking Janus kinase enzymes involved in the inflammatory process of RA.
• Before starting Xeljanz, patients should undergo screening for tuberculosis and other infections, as the medication can increase infection risk.
• Regular blood monitoring is necessary to check for potential side effects like decreased white blood cell count, elevated liver enzymes, or lipid abnormalities.
• Patients should be aware that Xeljanz carries boxed warnings for serious infections, malignancy, major adverse cardiovascular events, and thrombosis.

Considerations

• Xeljanz can be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs.
• It should not be taken with biological DMARDs or potent immunosuppressants like azathioprine and cyclosporine.
• The decision to prescribe Xeljanz should be based on an aggregate of contraindications, patient preference, and costs, as well as consideration of the potential risks and benefits, including the risk of thromboembolic events, particularly in patients with high risk factors 1.

Monitoring and Safety

• Regular monitoring of patients on Xeljanz is necessary to check for potential side effects and to assess the effectiveness of treatment.
• Patients should be closely evaluated during any tapering of Xeljanz, and if a flare occurs, the prior regimen should be reinstituted promptly.
• The potential risks and benefits of Xeljanz should be carefully considered, particularly in patients with a history of serious infections, malignancy, or cardiovascular events.

From the FDA Drug Label

XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more TNF blockers

Limitations of Use: Use of XELJANZ/XELJANZ XR in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

XELJANZ is indicated for the treatment of adult patients with moderately to severely active RA who have had an inadequate response or intolerance to one or more TNF blockers. However, its use is not recommended in combination with biologic DMARDs or potent immunosuppressants. 2

From the Research

XELJANZ for RA

• XELJANZ (tofacitinib) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3 3.
• It 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, 4.
• Clinical studies have shown that tofacitinib monotherapy and combination therapy with a conventional synthetic DMARD (csDMARD) are effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL) 3, 4.
• Tofacitinib has been shown to inhibit progression of structural damage in methotrexate-naïve patients and in patients receiving tofacitinib plus methotrexate as second-line therapy 3.
• 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) 3, 4.
• However, the incidence of herpes zoster (HZ) is higher with tofacitinib than in the general RA population, although infections are clinically manageable 3, 5.

Comparison with Other Treatments

• Tofacitinib has been compared to adalimumab in terms of efficacy and tolerability, with results showing that tofacitinib is noninferior to adalimumab when added to background methotrexate 3.
• Sarilumab, a monoclonal antibody against the interleukin-6 (IL-6) receptor, has also been shown to be effective in reducing signs and symptoms of RA and improving physical function when administered in combination with csDMARD therapy 6, 7.
• Sarilumab has been compared to placebo and has demonstrated statistically significant improvements in ACR20 response rates, HAQ DI, and radiographic damage 6.