Treatment of Inflammatory Myopathy
Start prednisone at 0.5-1 mg/kg/day (typically 60-80 mg daily) for 2-4 weeks concurrent with a steroid-sparing immunosuppressive agent from day one—never use corticosteroid monotherapy as it fails in 86% of patients. 1
Initial Treatment Protocol
Corticosteroid Dosing Strategy
- Use higher doses (closer to 1 mg/kg) for patients at high risk of relapse and low risk of adverse events 2, 1
- Use lower doses (closer to 0.5 mg/kg) for patients with diabetes, osteoporosis, or glaucoma 2, 1
- Administer as a single daily dose for 2-4 weeks before beginning taper 2, 1
- For severe weakness, dysphagia, or respiratory muscle involvement, add IV methylprednisolone 10-20 mg/kg (250-1000 mg) for 1-5 consecutive days 2, 3
Mandatory Concurrent Steroid-Sparing Agent (Start Day One)
Methotrexate (First-line for most patients without lung disease):
- Start at 15 mg orally once weekly with 1 mg/day folic acid supplementation 2, 1
- Increase to target dose of 25 mg weekly within 3-6 months 2, 3
- Screen for hepatitis B/C and baseline liver function tests before initiating 2
- Counsel patients to avoid excessive alcohol use 2
- Women of childbearing potential require reliable contraception (teratogenic) 2
Azathioprine (Preferred for interstitial lung disease or pregnancy planning):
- Check thiopurine methyltransferase level before starting 4
- Target dose of 2 mg/kg ideal body weight 2, 3
- Takes 3-6 months to reach full efficacy 3, 4
Mycophenolate mofetil (Preferred for severe dermatomyositis skin disease):
- Start at 500 mg twice daily 2, 1
- Increase by 500 mg weekly (or every 2 weeks based on tolerability) to goal of 1000 mg twice daily 2
- May increase to 1500 mg twice daily if tolerated 2
- Monitor for leukopenia and transaminitis 2
- Women of childbearing potential require two reliable forms of contraception (teratogenic) 2
Systematic Prednisone Tapering Schedule
Begin tapering after 2-4 weeks based on clinical response—never continue high-dose steroids beyond this initial period: 2, 1
- 60 mg/day → 40 mg/day (every 2 weeks)
- 40 mg/day → 30 mg/day (every 2 weeks)
- 30 mg/day → 25 mg/day (every 2 weeks)
- 25 mg/day → 20 mg/day (every 2 weeks)
- 20 mg/day → 17.5 mg/day (every 2 weeks)
- 17.5 mg/day → 15 mg/day (every 2 weeks)
- 15 mg/day → 12.5 mg/day (every 2 weeks)
- 12.5 mg/day → 10 mg/day (every 2 weeks)
- 10 mg/day → 7.5 mg/day (every 2 weeks)
- 7.5 mg/day → 5 mg/day (every 2 weeks)
- 5 mg/day → 2.5 mg/day (every 2 weeks)
- 2.5 mg/day → 0 mg/day (every 2 weeks) 2, 1
Treatment for Severe or Refractory Disease
Intravenous Immunoglobulin (IVIG):
- Indicated for dysphagia, notable weight loss, severe rash, or weakness 2
- Dose: 1-2 g/kg ideal body weight over 2 consecutive days (1 g/kg each day) 2
- Administer once monthly for 1-6 months 2
- Check serum IgA level before administering (IgA deficiency may cause severe infusion reactions) 2
- Controlled trial evidence supports efficacy in dermatomyositis 5, 6
Rituximab:
- Two 1000-mg doses given 2 weeks apart for adults 2
- The Rituximab in Myositis study showed 83% favorable response in refractory disease 2
- Obtain baseline immunoglobulin levels (IgG, IgM, IgA), hepatitis B/C antibodies, and screen for latent tuberculosis before administering 2
- Monitor for progressive multifocal leukoencephalopathy risk 2
Cyclophosphamide (for severe ILD or refractory disease):
- Infusions given every 4 weeks for 3-6 months (may extend to 12 months) 2
- Oral mesna given 4 and 8 hours after infusion (20% of cyclophosphamide dose) to reduce hemorrhagic cystitis risk 2
- Monitor white blood cell count for nadir at 8-14 days post-infusion (avoid nadir <3.0 x 10⁹/L) 2
- Patients must maintain adequate hydration (2-3 L within 24 hours) 2
Cyclosporine/Tacrolimus:
- Reserve for severe, refractory disease due to serious adverse effects including hypertension and renal insufficiency 2
- Monitor serum trough levels routinely to avoid renal toxicity 2
Pediatric Dosing (Juvenile Dermatomyositis)
- Prednisone: 2 mg/kg/day up to maximum of 60 mg/day 2, 1
- Subcutaneous methotrexate: 15 mg/m² once weekly from treatment onset 2, 1
- Taper corticosteroids by reducing from 2 mg/kg every 2 weeks until reaching 0.5 mg/kg, then taper by 10-20% of current dose for 4 weeks until completion 2
- For body surface area ≤1.5 m²: IVIG 575 mg/m² per infusion 2
- For body surface area >1.5 m²: IVIG 750 mg/m² up to 1 g per infusion 2
Critical Monitoring Requirements
- Regular muscle strength testing and creatine kinase levels 1, 4
- Functional capacity and activities of daily living assessments 3
- MRI with T2-weighted and fat suppression sequences to assess muscle inflammation 3, 4
- Screen for steroid-related complications (bone health with DEXA scan, prescribe calcium and vitamin D supplements, add bisphosphonate if osteoporosis present) 4
- Consider Pneumocystis prophylaxis and update vaccines before starting immunosuppressants 4
Critical Pitfalls to Avoid
- Never use corticosteroid monotherapy—it fails in 86% of cases 1, 3
- Never delay initiation of steroid-sparing agents—start on day one, not after corticosteroid failure 1, 3
- Never continue high-dose corticosteroids beyond 2-4 weeks—increases morbidity without improving outcomes 1, 3
- Never use initial prednisone doses >30 mg/day or ≤7.5 mg/day 1
- Avoid prolonged administration of high-dose corticosteroids 7
Special Populations
Inclusion Body Myositis:
- Generally resistant to standard immunotherapy 5, 8
- A trial of prednisone with methotrexate is reasonable for newly diagnosed patients 1, 7
- Early initiation of therapy may be helpful in some cases 5
Anti-HMGCR-Associated Myopathy:
- Requires aggressive combination therapy from the outset—rarely responds to corticosteroids alone 3
- Follow same initial protocol with mandatory concurrent immunosuppression 3
Immune-Mediated Necrotizing Myopathy: