Can Repatha (evolocumab) cause muscle pains?

Repatha (Evolocumab) and Muscle Pain

Yes, Repatha (evolocumab) can cause muscle pain (myalgia), which is documented in clinical trials as an adverse effect occurring in 4.0% of patients compared to 3.0% in placebo groups. 1

Evidence from FDA Label and Clinical Trials

Muscle-related adverse effects from Repatha include:

• Myalgia (muscle pain): Reported in 4.0% of Repatha-treated patients versus 3.0% in placebo groups in a 52-week controlled trial 1
• Musculoskeletal pain: Occurred in 3.3% of Repatha-treated patients versus 3.0% in placebo groups 1
• Muscle spasms: Reported in 1.3% of Repatha-treated patients versus 1.2% in placebo groups in pooled 12-week trials 1
• Back pain: Reported in 6.2% of Repatha-treated patients versus 5.6% in placebo groups 1

Importantly, myalgia was the most common adverse reaction leading to discontinuation of Repatha treatment (0.3% versus 0% for placebo) 1.

Mechanism and Risk Assessment

The mechanism of muscle pain with Repatha differs from statin-induced myopathy:

• Unlike statins, which can cause myopathy through interference with muscle cell metabolism, Repatha works by inhibiting PCSK9 (proprotein convertase subtilisin/kexin type 9)
• Muscle-related symptoms with Repatha are generally milder than statin-induced myopathy
• The risk of severe myopathy or rhabdomyolysis with Repatha appears to be very low

Clinical Approach to Patients with Muscle Pain on Repatha

Evaluation

When a patient on Repatha reports muscle pain:

1. Assess severity and distribution of muscle pain
2. Check for other symptoms such as weakness (which would suggest myositis rather than simple myalgia)
3. Consider laboratory testing:
   • Creatine kinase (CK) levels
   • Inflammatory markers (ESR, CRP) if clinically indicated
   • Liver function tests

Management Algorithm

1. For mild muscle pain without elevated CK:

   • Continue Repatha
   • Consider acetaminophen or NSAIDs for pain relief if no contraindications 2
   • Monitor symptoms

2. For moderate muscle pain or mildly elevated CK:

   • Consider temporary interruption of Repatha
   • Assess for other contributing factors (exercise, other medications)
   • Rule out other causes of myalgia
   • Consider rechallenge after symptoms resolve

3. For severe muscle pain or significantly elevated CK:

   • Discontinue Repatha
   • Consider referral to rheumatology or neurology
   • Evaluate for alternative lipid-lowering strategies

Important Considerations

• Concomitant statin therapy: Patients taking both statins and Repatha may have an increased risk of muscle symptoms. Consider whether symptoms began after adding Repatha to existing statin therapy.

• Drug interactions: Unlike statins, Repatha has fewer drug interactions that might increase the risk of myopathy 1

• Distinguishing from statin-induced myopathy: If a patient is on both medications, it's important to determine which drug is causing the symptoms. Statin-induced myopathy is more common and well-documented 2

• Monitoring: No routine CK monitoring is required for patients on Repatha without symptoms 1

Clinical Perspective

In meta-analyses comparing Repatha to ezetimibe, Repatha actually showed fewer muscle-associated events than ezetimibe 3, suggesting it may be a better option for patients with statin-associated muscle symptoms.

While muscle pain can occur with Repatha, the benefits of significant LDL-C reduction (60-75%) and cardiovascular risk reduction must be weighed against this potential side effect, which is generally mild and affects a small percentage of patients.