Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Membranous glomerulonephritis.
Treatment: HP Acthar Gel, Pre-service.

The insurer denied the HP Acthar Gel, Pre-service.  The denial is upheld. 

The patient is a male with diabetes. He has stage III chronic kidney disease due to membranous glomerulonephritis diagnosed by renal biopsy.  The patient was previously treated with mycophenolate, which was reportedly ineffective.  The patient stated that he used Acthar in the past, and that it resulted in any improvement in creatinine and proteinuria.  Acthar gel was prescribed.

No, the proposed treatment is not medically necessary.

Standard therapy for membranous glomerulonephritis, for which extensive data have been published over the last 20 years, include the Ponticelli protocol (corticosteroids with chlorambucil, or alternatively corticosteroids with Cytoxan), rituximab, and calcineurin inhibitor therapy (cyclosporine, tacrolimus). The patient has failed mycophenolate.

In a ten-year follow-up of one of the original studies in membranous glomerulonephritis by Claudio Ponticelli, treated patients (using steroids and chlorambucil or Cytoxan) had a higher likelihood of complete or partial remission (88 versus 47% in the placebo group) and a greater likelihood of surviving without renal failure (92 versus 60%).

A prospective randomized trial evaluated the efficacy of cyclosporine in 51 patients unresponsive to a six-month course of daily corticosteroid therapy. All patients received prednisone and were randomly assigned to either placebo or cyclosporine. The administration of cyclosporine was associated with a higher proteinuria remission rate at both 26 weeks (68 versus 22% for placebo) and 78 weeks (43 versus 19%). Rituximab has also shown to be efficacious in treatment of membranous glomerulonephritis.

In one study, 15 patients with severe nephrotic syndrome from membranous glomerulonephritis (seven of whom had failed prior immunosuppressive therapy) were treated with rituximab, and at 12 months, eight of the patients achieved complete or partial remission. Adverse effects were minor and primarily consisted of infusion reactions.

An observational study included 20 patients with membranous glomerulonephritis (with proteinuria over 5 g [grams] per day) who had failed prior therapy and were treated with rituximab for six months. At 12 months, complete or partial remission was noted and 10 patients and at 24 months, 16 patients had achieved either a partial or complete remission.

Other studies have demonstrated that rituximab administration in this condition causes a dramatic reduction in or disappearance of PLA2R (Phospholipase A2 Receptor) antibodies in the majority of patients; these antibodies are felt to be predictors of clinical response to therapy in membranous glomerulonephritis.

The data for use of Acthar gel for membranous glomerulonephritis include only uncontrolled reports and one small randomized controlled trial. These do show an improvement in proteinuria. One study of 14 patients with membranous glomerulonephritis treated with Acthar for 56 days found a 90% reduction in albuminuria at 56 days; it was found, however, that deterioration was observed in all cases when the drug was discontinued after this treatment duration. This was further examined in a randomized trial of 32 nephrotic patients with membranous glomerulonephritis in whom one year of therapy with Acthar was associated with complete or partial remission in 87% (compared to 93% in the standard (chlorambucil) therapy group).  It is notable that there are no data on long-term outcomes with Acthar in membranous glomerulonephritis and no data on its use in treatment-resistant disease. Additionally, no study demonstrates it to be superior to standard therapies supported by a greater body of published data.

Acthar does not have FDA (United States Food and Drug Administration) indication for treatment of membranous glomerulonephritis. Although data do suggest that a reduction in proteinuria occurs in many cases in which the drug is used to treat membranous glomerulonephritis, there are no long-term outcomes data (in regard to safety and efficacy). Finally, the drug has not been shown to be superior to existing treatments, and at least one study demonstrated that the beneficial effect of the drug is lost upon discontinuation (much like calcineurin inhibitors). In summary, Acthar is not medically necessary.