Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Chronic active Epstein-Barr virus (EBV)
Treatment: Jakafi
The insurer denied Jakafi
The determination is overturned.

This is a female patient with a history of chronic Epstein Barr Virus (EBV) infection. The patient has had severe inflammation and is being evaluated for possible allogeneic stem cell transplant (SCT). She has had several years of autoimmune dysregulation with coronary artery vasculitis, myocarditis, coronary vasodilation, dilation of the right ventricle with pulmonary hypertension, uveitis, immunoglobulin (Ig) A nephropathy, nephritis, leukopenia, thrombocytopenia. She is considered to have a lymphoproliferative type of condition with very poor prognosis and debilitating symptoms. The provider has stated that the only known cure is the SCT, but given the degree of inflammation that she currently has, this makes the SCT more risky for her situation. A multidisciplinary conference has actually recommended a liver transplant in addition to the SCT. The provider is now recommending treatment with Jakafi (ruxolitinib) to help control the inflammation but inhibiting the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Jakafi is under review.

This patient has significant inflammation related to an underlying chronic active EBV infection that needs to be treated with stem cell transplant (SCT) and liver transplant, but due to the degree of inflammation is not likely to survive this treatment at this time. The provider has recommended Jakafi as the best approach, given the patient's high chemokine ligand 9 (CXCL9) levels and oral administration. The provider feels that this may help control the patient's fever and tachycardia and stabilize the hepatopulmonary syndrome. Other options include Gamifant, or tacrolimus, but they are not likely to be as effective as the Jakafi.
The provider has given information from Onozawa et al in 2018 showing that STAT3 is activated in patients with chronic active EBV infection, providing a potential therapeutic target. Song et al showed that treatment of chronic active EBV with ruxolitinib as a compassionate use product resulted in clinical improvement for 7 out of 9 patients, noting that this was an effective and safe option for controlling the inflammatory symptoms in this disease process. It was specifically noted to be useful as a bridge to get to allogeneic stem cell transplant.
In 2022, Uemura et al published results from a phase II study of ruxolitinib in the chronic active EBV infection, and concluded that for the 9 patients treated with ruxolitinib, that this product demonstrated "encouraging effects" and was a "potent therapeutic reagent against" this disease process for those with active disease.
While allogeneic stem cell transplantation (SCT) is the only potential curative treatment option for this condition, the patient's current clinical status makes the likelihood of success of this treatment very low. The inflammation needs to be better controlled in order for the chance of a successful transplant to improve. There are no alternative options that are likely to be more beneficial than any other treatment for this patient's life-threatening condition. Therefore, based on the clinical information provided for review and the current peer-reviewed literature, the requested Jakafi 10 mg is likely to be more beneficial than standard treatment(s) at this time.