What is the best treatment for knee pain likely due to Calcium Pyrophosphate Deposition Disease (CPPD) that is refractory to a prednisone course?

Treatment for Knee Pain Due to CPPD Refractory to Prednisone

For patients with knee pain due to CPPD that is refractory to prednisone, methotrexate (5-10 mg/week) is the recommended treatment option based on the most recent evidence. 1

Treatment Algorithm for CPPD Refractory to Prednisone

First-Line Options (After Prednisone Failure):

• Methotrexate (5-10 mg/week)

  • Demonstrated significant decrease in pain intensity and joint counts in refractory cases 1
  • Clinical improvement typically observed within 7.4 weeks 2
  • All patients in a small study reported excellent clinical response with marked improvement 2

• Hydroxychloroquine

  • Alternative option with NNT for clinical response of 2 (95% CI 1 to 7) 1
  • Consider when methotrexate is contraindicated

Second-Line Options:

• Low-dose colchicine (0.5 mg up to 3-4 times daily)
  • NNT of 2 at 4 months for >30% pain reduction 1
  • Caution: Monitor for diarrhea and other gastrointestinal side effects
  • Dose adjustment required in patients with renal impairment 3

Third-Line Options (For Highly Refractory Cases):

• IL-1 inhibitors (e.g., anakinra) 4
  • Consider when other anti-inflammatory therapies are ineffective or contraindicated
  • Limited evidence but promising for refractory cases

Important Considerations

Methotrexate Benefits:

• Works as both an immunosuppressant and potent anti-inflammatory agent 2
• Effective at low doses (5-10 mg/week) 1
• Significant decrease in:
  • Pain intensity (p<0.0001)
  • Swollen and tender joint counts (p<0.0001)
  • Frequency of attacks 2

Safety Profile:

• Methotrexate is generally well-tolerated at low doses 2
• Monitor for common side effects:
  • Nausea
  • Fatigue
  • Elevated liver enzymes
  • Bone marrow suppression

Special Populations:

• Elderly patients: Require careful monitoring due to increased risk of side effects
• Renal impairment: Dose adjustment or alternative therapy may be necessary
• Patients with comorbidities: Individualized monitoring based on specific conditions

Addressing Underlying Factors

• Evaluate and treat any underlying metabolic disorders that may contribute to CPPD:
  • Hyperparathyroidism
  • Hemochromatosis
  • Hypomagnesemia
  • Hypophosphatemia 1

Treatment Duration

• Long-term therapy is typically required
• Mean follow-up time in studies was 50.4 months (range 6-81 months) 2
• Regular monitoring for efficacy and side effects is essential

While the evidence base for CPPD treatment is not as robust as for other rheumatologic conditions, methotrexate has shown the most promising results for patients with CPPD that is refractory to prednisone, with significant improvement in pain, joint swelling, and frequency of attacks.