Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Skin Disorders 
Treatment: Pharmacy/Prescription Drugs 
The insurer denied: Dupixent 
The denial is: Upheld in whole 

The patient is a male with atopic dermatitis (AD) affecting 30% body surface area (BSA). The patient has failed topical steroids, phototherapy and Tacrolimus. The provider requests Dupixent. 

The health plan's determination is upheld in whole. 

Dupixent is not medically necessary. Dupixent is Food and Drug Administration (FDA) approved for the treatment of moderate to severe atopic dermatitis in patients over the age of 12. Standard treatment options for patients with atopic dermatitis include a regimen of topical steroids as well as topical calcineurin inhibitors. After topical agents fail, standard practice is to pursue systemic therapy such as phototherapy. 

According to Wong et al., (2017) "Topical agents are the mainstay of treatment for mild-moderate AD and include TCS and topical calcineurin inhibitors (TCI). TCS are effective agents in addressing the pruritus and inflammation of AD and work by inducing inhibitory proteins that decrease inflammatory mediator activity. For patients with moderate-to-severe disease refractory to topical therapy, consideration should be given to the use of phototherapy or systemic immunomodulatory agents. Narrow-band ultraviolet B (UVB) (wavelength = 311 nanometer [nm]) is the most commonly used type of phototherapy for AD and is typically administered 2 to 3 times per week. Narrow-band UVB is a safe option that can provide relief from the signs and symptoms of AD Cyclosporine A is a calcineurin inhibitor that controls T-cell mediated inflammation by preventing the transcription of inflammatory cytokines. Cyclosporine A has been found to be effective in the management of severe and refractory AD in adults and children. Methotrexate, azathioprine and mycophenolate mofetil are antimetabolite medications that work as a folate antagonist, purine analog and purine synthesis inhibitor, respectively. These medications have been shown to be variably effective in treatment-resistant AD." 

Per Berth-Jones, "Thirty-seven subjects were enrolled, mean age 38 years (range 1773). Sixteen were withdrawn, 12 during azathioprine treatment and four during placebo treatment. The SASSAD score fell by 26% during treatment with azathioprine vs. 3% on placebo (probability [P] less than[<] 0.01). Pruritus, sleep disturbance and disruption of work/daytime activity all improved significantly on active treatment but not on placebo. The difference in mean improvement between azathioprine and placebo was significant for disruption of work/daytime activity (P < 0.02) but not for pruritus or sleep disturbance. Gastrointestinal disturbances were reported by 14 patients during azathioprine treatment and four were withdrawn as a result of severe nausea and vomiting. Leukopenia was observed in two patients and deranged liver enzymes in eight during treatment with azathioprine. Azathioprine is an effective and useful drug in severe AD although it is not always well tolerated. Monitoring of the full blood count and liver enzymes is advisable during treatment." 

Per Grundmann (2011), "Clinical efficacy was measured every 2 weeks using the subjective SCORAD index. Treatment with mycophenolate notably reduced the severity of AD within 4 weeks in all patients (P < 0.01). One patient had to discontinue mycophenolate therapy after 4 weeks because of the development of herpes retinitis. Except for this event, mycophenolate was tolerated well in all patients. Six of 7 patients who had responded to mycophenolate monotherapy had no relapse of disease during 20-week follow-up. In the 7 patients who finished the study, the SCORAD index was reduced by 74%, from 44.0 plus or minus () 7.8 before treatment to 11.4  5.9 at 20-week follow-up. Mycophenolate is a highly effective drug for treating moderatesevere AD, with no serious adverse effects occurring in any patients. Thus, mycophenolate might develop into a promising alternative in the therapy of moderate-severe AD."
Finally, per Dvorakova concerning Methotrexate in the pediatric population, "Forty-seven children were started on methotrexate for AD during this period. The mean Investigator Global Assessment (IGA) at the 3 to 5 month follow up improved from 4.25 to 2.8, with further improvement to 1.9 in the patients that continued therapy beyond 10 months. Changes in the Children's Dermatology Life Quality Index (CDLQI) mirrored changes in the IGA, with improvement in the mean CDLQI from 14.4 at the start of the treatment to 7.5 at the 3 to 5 month follow up. Further improvement in the CDLQI to 6.6 in patients who continued methotrexate beyond 10 months confirmed continued improvement in disease control beyond medium term therapy. The treatment was well tolerated. Methotrexate appears to be an effective, safe treatment for severe pediatric AD. Its therapeutic effects continue beyond the medium term treatment period, as reflected by further improvement in IGA and CDLQI scores in patients who continued methotrexate therapy beyond 10 months." 

The patient has no documented history of liver disease or elevated liver function tests (LFTs). The patient is not immunosuppressed or immunocompromised. The patient has no documented contraindication, intolerance, or failure (CIF) to any systemic immunosuppressive medication. Dupixent is not medically necessary.