Tofacitinib Should Not Be Used as First-Line Therapy for Rheumatoid Arthritis
Tofacitinib (Xeljanz) should not be used as first-line therapy for rheumatoid arthritis and should primarily be considered after biological DMARDs have failed. 1
Positioning of Tofacitinib in Treatment Algorithm
- Tofacitinib is a JAK inhibitor classified as a targeted synthetic DMARD (tsDMARD), not a conventional synthetic DMARD (csDMARD) or biological DMARD (bDMARD) 1
- The European League Against Rheumatism (EULAR) guidelines specifically recommend that tofacitinib should be considered only after biological treatment has failed 1
- Despite approval in some countries (USA, Japan, Russia, Switzerland) for use after failure of csDMARDs, safety concerns have led to recommendations against first-line use 1
Efficacy Considerations
- Tofacitinib has demonstrated efficacy in improving clinical, functional, and structural outcomes in rheumatoid arthritis 2
- As monotherapy or in combination with csDMARDs, tofacitinib has shown effectiveness in reducing disease symptoms and improving health-related quality of life 2, 3
- In patients with inadequate response to prior DMARDs, tofacitinib 5 mg twice daily has demonstrated significant improvements in ACR20/50/70 response rates and physical function compared to placebo 3
Safety Concerns Limiting First-Line Use
- Limited long-term safety data is available compared to established csDMARDs and bDMARDs 1
- Clinical trials have revealed a numerical increase in serious infection rates compared with controls 1
- Herpes zoster infections appear to be more common with tofacitinib than with TNF inhibitors 1, 4
- Several cases of tuberculosis and non-TB opportunistic infections have been reported 1
- Hematologic abnormalities including lymphocytopenia and anemia have been observed 1
Treatment Sequence Recommendations
- First-line therapy should involve conventional synthetic DMARDs, particularly methotrexate 1
- If treatment targets are not reached with csDMARDs, biological DMARDs should be considered before tofacitinib 1
- After failure of biological DMARDs, tofacitinib may be considered as a treatment option 1
- Some evidence suggests tofacitinib may have greater efficacy and an improved benefit/risk profile in those with fewer prior treatments, but this does not override safety concerns for first-line use 5
Cost Considerations
- The annual cost of tofacitinib (approximately US$25,000) is similar to biological agents 1
- Cost-effectiveness analyses comparing tofacitinib to established first-line therapies are needed 6
- The availability of biosimilars at potentially lower costs may influence treatment sequencing decisions 1
Monitoring Requirements
- If tofacitinib is used (after biological treatment failure), close monitoring for infections, particularly herpes zoster, is essential 1, 4
- Regular monitoring of complete blood counts is necessary due to potential hematologic abnormalities 1
- Patients should be screened for tuberculosis before initiating therapy 1
In conclusion, while tofacitinib is an effective treatment option for rheumatoid arthritis, current guidelines and safety considerations support its use only after biological DMARDs have failed, not as first-line therapy.