How to manage elevated Creatine Phosphokinase (CPK) levels in patients taking Repatha (Evolocumab)?

Management of Elevated CPK with Repatha (Evolocumab)

For patients with elevated Creatine Phosphokinase (CPK) levels while taking Repatha (evolocumab), continue Repatha therapy as it is safe and effective even in patients with markedly elevated CPK levels.

Assessment of Elevated CPK in Patients on Repatha

Diagnostic Evaluation

• Measure CPK levels to determine severity:
  • Grade 1 (mild): Normal CPK with muscle symptoms
  • Grade 2 (moderate): CPK 3-10× upper limit of normal (ULN)
  • Grade 3-4 (severe): CPK >10× ULN or severe symptoms 1

Rule Out Alternative Causes

• Evaluate for other causes of CPK elevation:
  • Recent strenuous exercise
  • Concurrent medications (statins, beta-blockers without ISA, certain antiepileptics)
  • Infections/febrile illness
  • Renal failure
  • Rheumatologic disorders
  • Hypothyroidism
  • Genetic muscular diseases 2
  • Recent trauma or intramuscular injections

Management Algorithm

Grade 1 (Mild Elevation with Symptoms)

1. Continue Repatha therapy - PCSK9 inhibitors are safe in patients with elevated CPK 2
2. Consider symptomatic treatment:
   • NSAIDs if no contraindications
   • Magnesium supplementation (300-400 mg elemental magnesium daily) 1
3. Monitor CPK levels every 4-6 weeks

Grade 2 (Moderate Elevation)

1. Continue Repatha therapy - Evidence shows 92% of patients with elevated CPK had reduction in CPK levels after starting PCSK9 inhibitors 2
2. Evaluate for concurrent medications that may contribute to CPK elevation
3. If patient was previously on statins:
   • Confirm statin has been discontinued
   • Note that PCSK9 inhibitors are specifically indicated for statin-intolerant patients 2
4. Monitor CPK levels every 2-4 weeks until improvement

Grade 3-4 (Severe Elevation)

1. Temporarily hold Repatha while conducting thorough evaluation
2. Assess for rhabdomyolysis (check renal function, urinalysis for myoglobinuria)
3. Consider neurology or rheumatology consultation 3
4. If no evidence of myositis or rhabdomyolysis:
   • Resume Repatha once acute issues resolved
   • Evidence shows PCSK9 inhibitors are safe even with markedly elevated CPK 2

Special Considerations

If Concurrent Myositis Suspected

• Complete muscle strength examination
• Consider EMG, MRI of affected muscles, or muscle biopsy if diagnosis uncertain 3
• If myositis confirmed:
  1. Hold Repatha temporarily
  2. Initiate prednisone 0.5-1 mg/kg/day if moderate symptoms
  3. For severe cases, consider higher dose steroids (1-2 mg/kg/day) 3
  4. Consider resuming Repatha once symptoms improve and CPK normalizes

Monitoring Recommendations

• Baseline CPK before initiating therapy
• Follow-up CPK measurement 4-6 weeks after starting therapy
• More frequent monitoring for high-risk patients:
  • Elderly (>65 years)
  • Multiple medications
  • History of muscle symptoms
  • Renal impairment 1

Key Insights

• Unlike statins, PCSK9 inhibitors like Repatha rarely cause muscle symptoms or CPK elevation 2
• In a study of patients with markedly elevated CPK (>1,000 U/L) who started PCSK9 inhibitors:
  • 92% showed >50% reduction in CPK levels
  • 46% had CPK levels return to normal
  • No serious adverse reactions were documented
  • Only 2 patients discontinued treatment (not due to muscle symptoms) 2

This evidence strongly supports continuing Repatha therapy in most patients with elevated CPK levels, as the medication is unlikely to be the cause and may actually help reduce CPK levels in patients previously affected by statin-induced myopathy.