Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Atopic Dermatitis.
Treatment: Dupixent 300MG/2ML SC SOPN, Pre-service.

The insurer denied the Dupixent 300MG/2ML SC SOPN, Pre-service.  The denial is overturned.

The patient is a man with severe atopic dermatitis using Dupixent every 2 weeks for approximately a year. It is no longer completely relieving his severe symptoms, and he requires an increasing frequency to weekly dosing. He presents with flaring of erythematous eczematous patches on bilateral hands, feet, and neck. He has previously tried and failed numerous treatments including betamethasone, mometasone, triamcinolone, Protopic, and clobetasol. Prior to starting Dupixent, more than 30% BSA (body surface area) was affected, EASI (Eczema Area and Severity Index) score 20, IGA (Investigator Global Assessment) 4. The plaques burnt, cracked, and bled. His skin disease does not improve with sunlight, and thus phototherapy would not be effective.

Yes, the Dupixent is medically necessary.

The patient has severe atopic dermatitis affecting multiple areas of the body. He has improved with dupilumab. Increasing the dosage to weekly administration is within the standard of care based on published literature.

Dupilumab is a monoclonal antibody that inhibits IL-4 (interleukin 4) and IL-13 (interleukin 13) signaling by blocking the shared IL-4Ra (interleukin 4 receptor) and originally demonstrated efficacy in phase II clinical trials. It was approved by the United States (US) Food and Drug Administration (FDA) for adults with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. It is a subcutaneous injection administered initially at a dose of 600 milligrams (mg) and then every two weeks thereafter.

Approval of dupilumab was based on clinical trials investigating dupilumab as monotherapy (SOLO 1 and SOLO 2) and in concomitant administration with topical corticosteroids (CHRONOS). Results from the SOLO 1 and SOLO 2 trials showed 36-38% of patients who received dupilumab had scores of zero or one (clear or almost clear) on the Investigator's Global Assessment scale compared with placebo (8-10%). Additionally, improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index (EASI) was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo.

Given its unprecedented efficacy, dupilumab is now a first-line therapeutic for moderate-to-severe atopic dermatitis (AD).

The patient in this case has failed topical steroids and calcineurin inhibitors.

Cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil are not Food and Drug Administration (FDA) approved for use in atopic dermatitis (Insufficient data exists to firmly recommend optimal dosing, duration of therapy, and precise monitoring protocols for any systemic immunomodulating medication. Strength of Recommendation: B Level of Evidence: I or II, depending on agent), while Dupixent is.

Systemic steroids and cyclosporine are not a reasonable long term treatment for moderate to severe atopic dermatitis due to their severe side effect profile.

There is evidence in the peer-reviewed published medical literature that supports weekly dosing of dupilumab in patients with severe atopic dermatitis as safe and effective.  In SOLO-CONTINUE, treatment-emergent ADA (antidrug antibodies) incidences were lowest with dupilumab weekly or every two weeks and were slightly higher with less frequent treatment regimens. In SOLO-CONTINUE, monotherapy with dupilumab, 300 milligrams, weekly or every two weeks for 36 weeks maintained the clinical efficacy achieved in SOLO and was significantly better than placebo across all outcomes. Less frequent administration (every four weeks or every eight weeks) resulted in reduced efficacy, no safety advantages, and numerically higher treatment-emergent ADA (antidrug antibody) incidences, whereas weekly administration had no apparent benefit over administration every two weeks. This study supports the use of 300 mg (milligrams) of dupilumab weekly or every 2 weeks as effective regimens in adults with moderate to severe AD (atopic dermatitis) for long-term maintenance of treatment response.

Furthermore, a prospective survey study assessed 23 patients with atopic dermatitis (AD) on dupilumab with standard every-other-week (EOW) dosing who were transitioned to every-week (EW) dosing. The average time from starting standard EOW (every other week) dupilumab to transitioning to EW (every week) dosing was 8.6 months. Overall, 5 of the 23 patients (22%) had Investigator Global Assessment (IGA) scores of clear or almost clear on EOW (every other week) dupilumab, while 12 of the 23 (52%) had IGA(Investigator Global Assessment) of clear or almost clear on EW (every week) dosing. Of the 17 who responded to the survey, 12 (71%) reported symptom recurrence prior to their next dupilumab dose on the EOW (every other week) dosing, and all patients claimed that increasing to EW (every week) dosing controlled their symptoms.

Weekly dosing of dupilumab may be beneficial to patients who experience recurrence of AD (atopic dermatitis) symptoms on the standard of every other week.

For the reasons above, Dupixent weekly injections are medically necessary.

No, the health plan did not act reasonably, with sound medical judgment, and in the best interest of the patient.