What are the guidelines for starting tofacitinib (Janus kinase (JAK) inhibitor) in patients with rheumatoid arthritis (RA)?

Guidelines for Starting Tofacitinib in Rheumatoid Arthritis

Tofacitinib should be considered only after biological DMARD treatment has failed in patients with rheumatoid arthritis, as it has less long-term safety data compared to other treatment options. 1

Treatment Algorithm for RA with Placement of Tofacitinib

First-Line Treatment

1. Methotrexate (MTX) should be part of the first treatment strategy for active RA

   • Start as soon as RA diagnosis is made 1, 2
   • Target optimal dosing (up to 25 mg weekly) before declaring treatment failure 2
   • For MTX contraindications or intolerance, use sulfasalazine or leflunomide 1, 2

2. Consider adding low-dose glucocorticoids as bridge therapy

   • Use for up to 6 months 1
   • Taper as rapidly as clinically feasible 1, 2

Second-Line Treatment (If First-Line Fails)

1. Without poor prognostic factors:

   • Switch to or add another conventional synthetic DMARD (csDMARD) 1
   • Consider triple therapy (MTX + sulfasalazine + hydroxychloroquine) 2

2. With poor prognostic factors (RF/ACPA positivity, high disease activity, early joint damage):

   • Add a biological DMARD (bDMARD) to MTX 1, 2
   • Options include:
     • TNF inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab)
     • IL-6 receptor blockers (tocilizumab, sarilumab)
     • T-cell costimulation inhibitor (abatacept)
     • Anti-B-cell agent (rituximab) in certain circumstances 1

Third-Line Treatment (After bDMARD Failure)

1. If first bDMARD fails:

   • Switch to another bDMARD 1
   • If first TNF inhibitor fails, can use another TNF inhibitor or a biological agent with another mode of action 1

2. After biological treatment failure:

   • This is when tofacitinib should be considered 1
   • Tofacitinib 5 mg twice daily is the recommended starting dose 3

Specific Considerations for Tofacitinib

Efficacy Profile

• Tofacitinib has shown efficacy in improving clinical, functional, and structural outcomes in RA 1, 3
• Efficacy is comparable to biologic DMARDs in patients with inadequate response to MTX 4
• Provides rapid improvement in pain and physical functioning, often within 2 weeks 5

Safety Considerations

• Monitor for infections, particularly herpes zoster which occurs at higher rates than with TNF inhibitors 1, 3
• Screen for tuberculosis before initiating therapy 2
• Monitor for changes in laboratory parameters:
  • Lymphocytopenia and anemia 1
  • Increased LDL and HDL cholesterol levels 6
  • Elevated serum creatinine 7

Drug Interactions

• Dose adjustments needed with CYP3A4 and CYP2C9 inhibitors/inducers 7
• Reduced dose (5 mg once daily) recommended when co-administered with potent CYP3A4 inhibitors 3

Monitoring Recommendations

• Assess response every 1-3 months in active disease 1, 2
• Adjust therapy if no improvement by 3 months or target not reached by 6 months 1, 2
• Regular laboratory monitoring for safety parameters

Common Pitfalls to Avoid

• Using tofacitinib as first-line therapy instead of MTX 1, 2
• Initiating tofacitinib before trying bDMARDs 1
• Inadequate monitoring for infections, particularly herpes zoster 1, 3
• Overlooking drug interactions with CYP3A4 and CYP2C9 inhibitors/inducers 7
• Failing to adjust therapy if treatment target is not reached within the recommended timeframe 2

By following this structured approach to RA treatment with appropriate placement of tofacitinib after biological treatment failure, clinicians can optimize outcomes while minimizing risks in patients with rheumatoid arthritis.