What is a suitable prescription for rheumatoid arthritis including methotrexate, tofacitinib, and hydroxychloroquine (HCQs)?

Rheumatoid Arthritis Prescription Regimen with Methotrexate, Tofacitinib, and Hydroxychloroquine

For patients with moderate-to-high disease activity rheumatoid arthritis, the recommended prescription should include methotrexate at 15 mg/week orally as the anchor therapy, escalating to 25-30 mg/week within 4-6 weeks, with hydroxychloroquine 200-400 mg daily, and tofacitinib 5 mg twice daily added if disease activity remains moderate-to-high after 3 months of optimized methotrexate therapy.

Methotrexate Regimen

• Start with oral methotrexate at 15 mg once weekly 1
• Escalate dose by 5 mg/month to reach 25-30 mg/week or highest tolerable dose 1
• Add folic acid 5 mg daily (except on methotrexate day) to reduce side effects 1
• If inadequate response to oral methotrexate or intolerable side effects, switch to subcutaneous administration at same dose 2
• Monitor complete blood count, liver function, and renal function every 1-1.5 months during dose escalation, then every 1-3 months 1

Hydroxychloroquine (HCQS) Regimen

• Add hydroxychloroquine 200 mg twice daily (400 mg/day) 2
• Maximum dose should not exceed 5 mg/kg/day based on actual body weight
• Requires baseline ophthalmologic examination and yearly screening after 5 years of use
• Monitor for rare but serious adverse effects including retinopathy and cardiomyopathy

Tofacitinib Addition

• Add tofacitinib 5 mg twice daily if inadequate response to optimized methotrexate + hydroxychloroquine after 3 months 2
• Assess response after 3 months of tofacitinib therapy 2
• Contraindicated in patients with serious active infections, severe hepatic impairment
• Use with caution in patients with risk factors for venous thromboembolism 2
• Monitor for infections, lipid abnormalities, and liver enzyme elevations

Treatment Algorithm

1. Initial Phase (0-3 months):

   • Start methotrexate 15 mg orally once weekly + hydroxychloroquine 200 mg twice daily
   • Escalate methotrexate by 5 mg monthly to target dose of 25-30 mg/week
   • Evaluate response at 3 months using validated disease activity measures

2. If inadequate response at 3 months:

   • Optimize methotrexate dosing (consider subcutaneous administration)
   • Add tofacitinib 5 mg twice daily 2

3. Monitoring Schedule:

   • Disease activity assessment every 1-3 months until target achieved 2
   • Laboratory monitoring (CBC, LFTs, creatinine) every 1-3 months 2
   • Once at target for 6 months, can consider less frequent monitoring (every 3-6 months)

Important Clinical Considerations

Efficacy

• Triple therapy with methotrexate, hydroxychloroquine, and sulfasalazine has shown similar efficacy to methotrexate plus biologics 3, but this prescription uses tofacitinib instead of sulfasalazine
• Tofacitinib has demonstrated superior efficacy compared to methotrexate monotherapy in reducing signs and symptoms of RA 4

Safety Precautions

• Methotrexate: Monitor for hepatotoxicity, bone marrow suppression, and pulmonary toxicity
• Hydroxychloroquine: Regular ophthalmologic screening to detect early retinopathy
• Tofacitinib: Increased risk of herpes zoster and venous thromboembolism; monitor for infections 2

Common Pitfalls to Avoid

1. Inadequate methotrexate optimization: Ensure methotrexate is properly optimized before adding tofacitinib 1
2. Insufficient folic acid supplementation: Always prescribe folic acid with methotrexate to reduce side effects
3. Lack of regular monitoring: Adherence to monitoring schedule is essential for early detection of adverse events
4. Failure to assess response: Evaluate disease activity systematically using validated measures every 1-3 months 2
5. Overlooking comorbidities: Screen for and address tuberculosis, hepatitis B/C before starting therapy

This prescription regimen follows the treat-to-target approach recommended by current guidelines, with the goal of achieving low disease activity or remission to improve long-term outcomes including reduced morbidity, mortality, and improved quality of life 2.