Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Anemia, Deficiency of Adenosine Deaminase
Treatment: Ruxolitinib
The insurer denied Ruxolitinib.
The determination is overturned.

This is a male patient with a diagnosis of deficiency of adenosine deaminase 2 (DADA2). Using genetic testing, the patient was found to have a homozygous mutation of Cat eye syndrome critical region protein 1 (CECR1) gene. This is a genetically transmitted disease. Patients with ADAD2 can present with ischemic or hemorrhagic stroke in small blood vessels, livedoid rash and hepatosplenomegaly. Patients can have recurrent fever, vasculopathy, stroke and immunodeficiency with bone marrow failure. The patient's major clinical manifestations are anemia as a result of pure red cell aplasia which requires regular blood cell transfusions every three weeks. This can result in iron overload from the frequent transfusions which requires chelation therapy. There is no established therapy to cure or manage this disease. Patients with vasculitis can respond to tumor necrosis factor (TNF) inhibitors. Hematopoietic stem cell transplant is used for patients with bone marrow failure. The patient does not have a suitable donor in the bone marrow registry. DADA2 has been found to have over expression of type 1 interferon-induced genes. This pattern is present in a number of genetic disorders including Aicardi-Goutieres Syndrome and STAT1-gain of function. Interferon signals via the janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Inhibitors of JAK have been used in these conditions. Ruxolitinib is an effective treatment for bone marrow failure syndrome associated with signal transducer and activator of transcription 1-gain-of-function (STAT1-GOF). This drug is commonly used in treating leukemia and in myelofibrosis, a bone marrow failure disease. There is ample evidence for the efficacy of Ruxolitinib for treatment of anemia in myelofibrosis (National Comprehensive Cancer Network (NCCN) guidelines for myelofibrosis). At issue is whether Ruxolitinib is likely to be more beneficial than any standard treatment or treatments for the insured's life threatening or disabling condition or disease.

Yes. There is no established therapy to cure or manage this disease. Patients with vasculitis can respond to TNF inhibitors. Hematopoietic stem cell transplant is used for patients with bone marrow failure. The patient does not have a suitable donor in the bone marrow registry. DADA2 has been found to have over expression of type 1 interferon-induced genes. This pattern is present in a number of genetic disorders including Aicardi-Goutieres Syndrome and STAT1-gain of function. Interferon signals via the JAK-STAT pathway. Inhibitors of JAK have been used in these conditions. Ruxolitinib is an effective treatment for bone marrow failure syndrome associated with STAT1-GOF. This drug is commonly used in treating leukemia and in myelofibrosis, a bone marrow failure disease. There is ample evidence for the efficacy of ruxolitinib for treatment of anemia in myelofibrosis (NCCN guidelines for myelofibrosis). The treating physician has requested approval for Ruxolitinib 5 milligrams (mg) by mouth (PO) twice daily (bid) for this patient.

There is ample evidence for the efficacy of Ruxolitinib in the treatment of anemia associated with bone marrow failure syndromes including myelofibrosis. DADA2 is an extremely rare genetic disease with approximately 1000 patients in the United States diagnosed with this disease. It is not possible to conduct a clinical trial to evaluate efficacy in such a rare disease so clinical data from more common bone marrow syndromes and other related genetic disease must be used to determine the best clinical standard of care.