Appeal type: Experimental/Investigational
Decision: Upheld

Diagnosis: Deficiency of Adenosine Deaminase
Treatment: Ruxolitinib
The insurer denied Ruxolitinib.
The determination is upheld.
This is a male patient with deficiency of adenosine deaminase 2 (DADA2). He has pure red cell aplasia and requires a red blood cell transfusion every 3 weeks. The provider states that patients with vasculitis are often responsive to tumor necrosis factor (TNF) inhibitors but those with bone marrow failure often require hematopoietic stem cell transplant. This patient does not have a donor for a transplant. The provider states that this disease is associated with over-expression of type 1 interferon-induced genes, and since interferon signals janus kinase (JAK)/signal transducer and activator of transcription (JAK-STAT) pathway, inhibitors of JAK are being used in these conditions. The provider has recommended treatment with Ruxolitinib. The use of Ruxolitinib is under review.

No, the proposed treatment with Ruxolitinib is not likely to be more beneficial than other standard treatment or treatments for the patient's life-threatening or disabling condition or disease.
This patient has developed an autoimmune cytopenia in the setting of his underlying DADA2 disease. As per a 2019 GeneReviews discussion of this topic, anti-tumor necrosis factor (TNF) agents such as etanercept, adalimumab, golimumab, infliximab, and certolizumab are the drugs of choice for symptomatic and asymptomatic patients with DADA2. They prevent and eliminate manifestations of auto inflammatory disease / vasculitis, reduce the risk of ischemic stroke, reduce inflammatory burden, and relieve immunodeficiency, Hepatosplenomegaly, and neutropenia. They also improve growth and development in affected children, and red blood cell and platelet counts. They do not have much effect in rescuing severe bone marrow abnormalities.
Looking at a 2022 review by Barron et al, while anti-tumor necrosis factor (TNF) agents are useful for many patients with DADA2 in general, these products have little impact on severe neutropenia or pancytopenia and carefully chosen targeted therapies that cause thymus-derived (T)-cell suppression may be useful. As per a recent 2022 review by Pacillo et al, ruxolitinib has been used in the treatment of autoimmune cytopenias in patients affected by gain-of-function Signal transducer and activator of transcription (STAT) 1 and STAT3 mutations with good response. It reduces the interferon-gamma activity and normalizes type 1 T helper (Th1) and T-follicular helper (Tfh) cell differentiation and improves T helper 17 (Th17) cell development, managing an effective control of immune dysregulation.
As per the clinical notes, the provider states "will start to pursue Ruxolitinib due to unpublished data on utility in transfusion dependent patients". However, there is no documentation that the patient has tried and failed steroids, or TNF agents. Without failure of other treatments of the condition, it cannot be noted that the proposed treatment with Ruxolitinib is likely to be more beneficial than any standard treatment for the patient's life-threatening of disabling condition or disease.
Therefore, while there is some literature to support this type of therapy in this general type of condition, it is not clear that the treatment or treatments of the insured's condition will be better with use of Ruxolitinib over the other agents that are considered more standard.