Appeal type: Formulary Exception
Decision: Overturned

Diagnosis: Monoallelic mutation in cytotoxic T-lymphocyte associated protein 4 (CTLA-4) gene

Treatment: Orencia 125 milligrams (mg)/milliliters (ml) syringe

The insurer denied coverage for Orencia 125 milligrams (mg)/milliliters (ml) syringe.

The denial is overturned.

This is a patient with a request for Orencia 125 milligrams (mg)/milliliters (ml) syringe. The patient has monoallelic mutation in cytotoxic T-lymphocyte associated protein 4 (CTLA-4) gene.

Prior denial noted it was determined that the service are not an acceptable alternative to formulary options and this decision is based on the following: Coverage is provided for rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis.

In an appeal letter, it's noted the patient is diagnosed with monoallelic mutation in cytotoxic T-lymphocyte associated protein 4 (CTLA-4) gene. The diagnosis of CTLA-4 deficiency was based on consistent clinical manifestations (bowel inflammation, abnormal immune workup showing significant immune dysregulation, and the family history that is consistent with autosomal dominant inheritance). The letter stated that Abatacept substitutes CTLA-4 and binds to its receptor and therefore, it treats the immune defect caused by the absence of a functional CTLA-4 protein.

Based on the medical records provided for review, it is not likely that the patient would have an adverse reaction to the formulary drug(s).      

The formulary drug has been ineffective based on the patient's clinical history. There is no Food and Drug Administration (FDA) approved medication for CTLA-4 deficiency. Orencia has been extensively shown to be effective and the alternative is likely to be ineffective.     

The requested drugs are more effective than the formulary drug. Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency is a very rare disease.  A study by Kiykim A et al., (2019) patients with LRBA deficiency and the use of abatacept was reviewed. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenia's. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy.  The authors concluded that Long-term abatacept therapy is effective in most patients with LRBA deficiency.

Per Lo et al., (2015)  "We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA-4 (cytotoxic T lymphocyte antigen-4)immunoglobulin fusion drug...In summary, therapy targeting CTLA-4 was highly effective in reversing life-threatening infiltrative and autoimmune disease in LRBA-deficient patients."

"To date, several germline mutations have been identified in the LRBA gene in patients suffering from a variety of clinical symptoms. These mutations abolish the expression of the LRBA protein, leading to autoimmunity, chronic diarrhea, B-cell deficiency, hypogammaglobulinemia, functional T-cell defects and aberrant autophagy" (Akhairy et al., 2016).

There is no FDA (Food and Drug Administration) approved medication for CTLA-4 deficiency. Orencia has been extensively shown to be effective and the alternative is likely to be ineffective. 

The formulary drugs are not expected to cause adverse effects. 

The formulary drugs were not tried, and the patient did not have an adverse reaction or contraindication.

The formulary drug is expected to be ineffective.

The non-formulary drug is expected to be more effective than the formulary alternatives.

The carrier's denial of a request for a Formulary Exception for Orencia 125 mg/ml syringe to treat monoallelic mutation in cytotoxic T-lymphocyte associated protein 4 (CTLA-4) gene is reversed.