What are the approved immunotherapies for treatment of myasthenia gravis in pediatric patients?

Approved Immunotherapies for Pediatric Myasthenia Gravis

Currently, there are no FDA-approved immunotherapies specifically indicated for pediatric myasthenia gravis, and treatment follows adult guidelines with dose adjustments, using corticosteroids as the primary immunosuppressive agent, followed by steroid-sparing agents like azathioprine, mycophenolate mofetil, and tacrolimus. 1, 2, 3

First-Line Immunotherapy Approach

Corticosteroids (prednisone) represent the most consistently effective immunosuppressive therapy for pediatric MG, with 66-85% of patients showing positive response. 1, 2

• Start prednisone at 0.5 mg/kg orally daily for Grade 2 disease (mild generalized weakness, symptoms interfering with activities of daily living) 1
• Corticosteroids should be initiated when pyridostigmine alone provides inadequate symptom control, which occurs in approximately 50% of pediatric patients 1, 3
• Taper should begin 3-4 weeks after initiation based on symptom improvement 4

Steroid-Sparing Immunosuppressive Agents

Azathioprine is the first-choice steroid-sparing immunosuppressant for pediatric MG, though it requires several months to achieve therapeutic effect. 2, 5

• Azathioprine can be used as monotherapy or adjunctive therapy with corticosteroids for moderate to severe disease 1, 2, 5
• Mycophenolate mofetil serves as a second-choice steroid-sparing agent when azathioprine is contraindicated or ineffective 3, 5
• Cyclosporine is another second-line option, though renal toxicity and hypertension limit its use 6, 5
• Tacrolimus has shown efficacy in open-label trials for juvenile MG refractory to prednisone, including ocular manifestations 3

Acute/Rescue Immunotherapies

For Grade 3-4 disease (moderate to severe weakness, respiratory compromise), IVIG at 2 g/kg IV over 5 days (0.4 g/kg/day) or plasmapheresis for 3-5 days should be initiated immediately. 4, 1, 2

• IVIG and plasmapheresis show no pronounced differences in efficacy and are recommended as adjunct therapy for MG exacerbations 6
• These therapies provide rapid but temporary benefit while waiting for long-term immunosuppression to take effect 7, 6
• Rituximab may be considered for refractory cases, though no specific reports exist for pediatric ocular MG 3

Novel Targeted Immunotherapies

Efgartigimod alfa-fcab is FDA-approved for AChR-positive adult MG but has not been specifically approved for pediatric use. 2, 8

• Other novel agents including eculizumab, rozanolixizumab, ravulizumab, and zilucoplan have been studied in adults but lack pediatric-specific approval 8
• These agents offer faster onset of action and more favorable side effect profiles compared to conventional immunosuppression 7, 8

Surgical Immunomodulation

Thymectomy should always be performed when thymoma is present and should be evaluated in appropriate AChR-positive pediatric patients. 1, 2

• Thymectomy is effective in controlling pediatric ocular MG and shows patterns toward preventing generalization, reducing prednisone dosing, and increasing disease resolution 3
• Thymectomy is recommended for patients below age 55-60 within the first 6-12 months of disease duration in non-thymomatous cases 6

Critical Medication Avoidance

Immediately discontinue β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolide antibiotics, as these worsen myasthenic symptoms. 4, 1, 2

Pediatric-Specific Considerations

• Approximately 25% of pediatric patients with ocular MG can achieve complete remission 3
• Rates of generalization from ocular to generalized MG range from 15-35%, with higher rates in adolescents 3
• Treatment was ultimately withdrawn in nearly 20% of anti-AChR positive early-onset patients, with the lowest rate of serious side effects (4%) in this population 5
• No pediatric randomized controlled trials have been performed for steroid-sparing agents or thymectomy in ocular MG 3