Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Angiofibroma
Treatment: Sirolimus Compound

The sirolimus compound is medically necessary; it is in accordance with generally accepted standards of good medical practice, it is clinically appropriate and considered effective, and it is not for the convenience of the patient or provider.

Facial angiofibromas, which occur in 70% to 80% of patients with tuberous sclerosis (TS or TSC), appear as innumerable pink papules that progressively enlarge and multiply over time. The lesions, which are highly visible markers of disease, may spontaneously bleed, impair vision, and cause emotional distress.  Current treatment options for facial angiofibromas include destructive approaches such as dermabrasion, surgical excision, and laser therapy.  A more targeted therapeutic approach is needed because current therapies are not effective in preventing early lesions and therefore may have less than satisfactory outcomes. It is also necessary to balance aggressive therapy against the risk of significant permanent scarring and risk of sedation with the seizures that roughly 80% of TS patients experience. 

Rapamycin, an immunosuppressant typically used in transplant patients, has antineoplastic effects that are exerted through the downregulation of angiogenesis and the correction of aberrant growth signals, which are implicated in many tumors and cancers.  Tuberous sclerosis is an autosomal dominant disease characterized by systemic hamartomas (tumors).  The defective genes normally inhibit the mammalian target of rapamycin (mTOR), which has numerous functions in the regulation of protein synthesis and cell growth. The constitutive activation of mTOR is associated with abnormal cellular proliferation, which causes TSC-related hamartomas.  Oral administration of Rapamycin is used for many of the systemic manifestations of TS, while topical rapamycin for treatment of cutaneous disease avoids the systemic exposure and adverse effects.  

The article referenced in 2010 (Arch Derm) was one case report.  The 2011 study documented improvement in two patients.   A prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston published in 2012 studied the use of topical Rapamycin in 23 subjects.  There was no detectable systemic absorption of rapamycin (all blood concentrations were less than [ ] < 1.0nanograms per milliliter [ng/mL]). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas.  The study concluded that the application of low-dose topical rapamycin (0.003-0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex. 

The safety and efficacy of this topical agent has also been confirmed in the randomized controlled trial published in 2017.  Given that other treatment options involve surgical removal or laser, this can be considered a safe and effective therapy for this condition.