How to manage myalgia in patients taking Dupixent (dupilumab)?

Management of Dupilumab-Associated Myalgia

For mild myalgia without weakness or elevated CK, continue dupilumab and initiate acetaminophen or NSAIDs for symptom control; for moderate-to-severe myalgia or any elevation in muscle enzymes, hold dupilumab immediately and escalate to corticosteroids if inflammatory myositis is confirmed. 1

Initial Diagnostic Workup

When a patient on dupilumab develops myalgia, immediately assess whether this represents simple muscle pain versus inflammatory myositis, as the latter can be life-threatening:

• Check creatine kinase (CK) and aldolase levels to evaluate for muscle inflammation; transaminases and LDH may also be elevated in myositis 2
• Obtain troponin levels to evaluate for myocardial involvement, as drug-induced myositis can affect the heart 2, 3
• Measure inflammatory markers (ESR, CRP) to assess for systemic inflammation 4
• Assess for true muscle weakness versus pain alone: weakness suggests myositis requiring urgent intervention, while pain without weakness indicates simple myalgia or polymyalgia-like syndrome 2
• Perform complete rheumatologic and neurologic examination including muscle strength testing in proximal extremities 2

Risk Stratification and Treatment Algorithm

Grade 1: Mild Myalgia (Normal CK, No Weakness)

• Continue dupilumab and monitor symptoms 2
• Initiate acetaminophen as first-line analgesia if no contraindications 4, 2
• Escalate to NSAIDs (ibuprofen 400-800 mg three times daily or naproxen 500 mg twice daily) if acetaminophen insufficient 2
• Monitor every 2-4 weeks with repeat CK if symptoms persist 2

Grade 2: Moderate Myalgia (Mildly Elevated CK or Persistent Symptoms)

• Hold dupilumab temporarily until symptoms resolve and CK normalizes 2
• Initiate prednisone 20 mg daily if symptoms are significant or CK is elevated 4
• Refer to rheumatology for further evaluation 4, 2
• May resume dupilumab only after symptoms resolve to grade 1 or less and in consultation with rheumatology 4

Grade 3-4: Severe Myalgia or Myositis (CK ≥3x Upper Limit Normal, Weakness Present)

• Permanently discontinue dupilumab - do not rechallenge if severe myositis occurred 2, 1
• Initiate prednisone 0.5-1 mg/kg/day (approximately 20 mg or higher depending on severity) 4, 2
• Urgent rheumatology consultation and consider admission for pain control and monitoring 4
• Consider corticosteroid-sparing agents (methotrexate) if prolonged high-dose steroids needed 4

Key Differentiating Features

The critical distinction is between simple myalgia and inflammatory myositis:

• Simple myalgia: Pain without weakness, normal CK, can continue dupilumab with symptomatic treatment 2, 1
• Inflammatory myositis: True proximal muscle weakness, markedly elevated CK, requires immediate dupilumab discontinuation 4, 2
• Polymyalgia-like syndrome: Severe proximal pain with fatigue but no true weakness, highly elevated inflammatory markers but normal CK 4, 5

Timeline and Clinical Pearls

• Onset typically occurs within 4 months of dupilumab initiation 6
• Most cases resolve within weeks after discontinuation 6
• Myalgia is a rare adverse effect of dupilumab, with arthralgia and back pain being more commonly reported 1
• One case report documented severe myalgia and muscle spasms requiring cessation despite good dermatologic response 1
• Rare cases of acute myocarditis with myalgia, fever, and elevated troponin have been reported 3

Medications to Avoid

• Do not use corticosteroids for simple myalgia without evidence of inflammatory myositis, as they lack efficacy and cause significant harm 2
• Avoid strong opioids for simple myalgia 2
• Consider pregabalin 75-150 mg twice daily only if neuropathic pain component is suspected 2, 7

Special Considerations

If the patient has concurrent conditions that may contribute to myalgia:

• Hold statins temporarily if patient is on concurrent statin therapy, as this may be contributing 2
• Screen for hypothyroidism as a reversible cause of myalgia 7
• Consider alternative biologics (JAK inhibitors) if dupilumab must be discontinued for severe arthritis or myalgia 6