Exondys 51 (Eteplirsen) is NOT Medically Necessary for This Patient
Continuation of Exondys 51 should not be certified for this 18-year-old patient because eteplirsen is only FDA-approved and clinically indicated for patients with DMD amenable to exon 51 skipping, not exon 50 deletion. This patient has a deletion of exon 50, which makes him ineligible for eteplirsen therapy, as the drug is specifically designed to skip exon 51 to restore the dystrophin reading frame in patients with mutations amenable to exon 51 skipping 1, 2, 3.
Critical Eligibility Issue: Wrong Genetic Mutation
Eteplirsen is a phosphorodiamidate morpholino oligomer (PMO) specifically designed to skip exon 51 and restore the dystrophin mRNA reading frame in patients with mutations amenable to exon 51 skipping 4, 3.
This patient has a deletion of exon 50, not a mutation amenable to exon 51 skipping, making him genetically ineligible for eteplirsen therapy 1, 2.
All clinical trials of eteplirsen (studies 201/202, PROMOVI) enrolled only patients with confirmed mutations amenable to exon 51 skipping, and efficacy data exist only for this specific genetic subset 2, 5, 3.
Evidence Base Supports Only Exon 51-Amenable Patients
The PROMOVI trial (n=78) and long-term studies demonstrated efficacy only in patients with mutations amenable to exon 51 skipping, showing increased exon skipping (18.7-fold) and dystrophin protein (7-fold) at 96 weeks 2.
Comparative studies showed eteplirsen-treated patients (exon 51-amenable) had significantly better 6MWT outcomes versus matched controls at Year 4 (difference of 159m, p=0.002), but these benefits apply only to the correct genetic population 5.
Natural history comparisons specifically noted that patients amenable to exon 51 skipping showed a more severe disease course than those amenable to other exon skipping, emphasizing the mutation-specific nature of the disease and treatment 3.
Appropriate Management for This Patient
The patient should continue glucocorticoid therapy (prednisone), which remains the cornerstone of DMD treatment even after loss of ambulation 6, 7.
Glucocorticoid Continuation Post-Ambulation
Glucocorticoids should be continued after loss of ambulation to preserve upper limb strength, reduce progression of scoliosis, and delay decline in respiratory and cardiac function 6, 7.
The patient is already on prednisone, which should be maintained at appropriate dosing (0.75 mg/kg/day or adjusted based on tolerability) to provide ongoing benefits for respiratory stabilization and scoliosis prevention 6.
Continued glucocorticoid use in non-ambulatory patients has demonstrated reduction in progressive scoliosis risk and stabilization of pulmonary function test variables 6.
Multidisciplinary Supportive Care
Aggressive respiratory management is essential given the patient's limited chest expansion and disease progression, including pulmonary function monitoring and consideration for nocturnal ventilation support as needed 6.
The patient requires cardiac monitoring given his age and disease stage, as DMD patients face significant cardiac complications; ACE inhibitors or ARBs should be considered if not already initiated 7.
Physical and occupational therapy should continue (currently receiving PT/OT 1x/week, aquatic therapy) to maintain upper extremity function and prevent contractures 6, 7.
Common Pitfall to Avoid
Do not prescribe mutation-specific therapies without confirming the exact genetic mutation amenable to that specific treatment. Eteplirsen works only for exon 51-amenable mutations, and using it for exon 50 deletion provides no therapeutic benefit while exposing the patient to unnecessary infusions and healthcare costs 1, 2, 3.