Appeal type: Medical necessity
Decision: Overturned

Diagnosis: X-Linked Lymphoproliferative Syndrome, Crohn's Disease, Recurrent 
Hemophagocytic Lymphohistiocytosis (HLH)-like Episodes. 
Treatment: ILaris 150 milligrams per milliliter (MG/ML) Vial. 

The insurer denied: ILaris 150 milligrams per milliliter (MG/ML) Vial. 
The denial is overturned. 

The patient is an adolescent male with medical history significant for X-linked lymphoproliferative syndrome (XLP-2), Crohn's disease, refractory to treatment on chronic steroids status post diverting ileostomy, recurrent hemophagocytic lymphohistiocytosis (HLH) with multiple admissions awaiting transplant (on hold due to social issues), attention deficit hyperactivity disorder (ADHD), and adjustment disorder. He has been unable to meet criteria for Tadekinig unless he is ill, but then he is too ill to travel to get the medication. The patient's treatment team, including the Bone Marrow Transplant team and Gastroenterology team, have created a treatment plan for the patient that involves treatment with canakinumab for hemophagocytic lymphohistiocytosis (HLH) flares and chronic inflammation, as well as infliximab for severe Crohn's disease. There are no Food and Drug Administration (FDA)-approved therapies for this young male, and the treating team has limited choices. The current request is for canakinumab. 

The proposed treatment is medically necessary. 

Canakinumab is an anti-interleukin (IL)-1beta monoclonal antibody currently under intensive investigation for treatment of IL-1beta-mediated autoimmune conditions. It has been Food and Drug Administration (FDA)-approved for the treatment of Muckle-Wells syndrome (MWS) and Familial Cold Auto-Inflammatory Syndrome (FCA), both cryopyrin-associated periodic syndromes. In addition to the three forms of arthritis mentioned above, it is also being evaluated in clinical trials for chronic obstructive pulmonary disease, type II diabetes, and macular degeneration. X-linked lymphoproliferative disease type II is characterized by the following three sequelae: inappropriate immune response to Epstein Barr Virus (EBV) with development of hemophagocytic lymphohistiocytosis (HLH); dysgammaglobulinemia; and lymphoproliferative disease (eg malignant lymphoma). The only curative treatment at this time is allogeneic hematopoietic cell transplantation. All of therapies involve management of the sequelae. For example, rituximab is used to treat hemophagocytic lymphohistiocytosis (HLH) when associated with Epstein Barr Virus (EBV) infection, lymphoma is treated with appropriate chemotherapeutic agents, and inflammatory bowel disease is treated with immunosuppression. Agents would include steroids, etoposide, anti-thymocyte globulin, rituximab, chemotherapy (for lymphoma), and intravenous immunoglobulin (IVIG). 

XLP-2 is a rare condition, and with the addition of all potential sequelae, it is an extremely rare condition. The definitive treatment, the only treatment, is transplant. To date, this patient has not qualified for transplant because of social complications. However, he is currently being re-evaluated for the one study drug available, Tadekinig. There are no other choices for treatment for this patient. His treatment team has researched extensively and have created a potential alternative treatment plan involving canakinumab. 

In the absence of other therapies, canakinumab has been chosen as the most likely agent to provide relief from chronic inflammation and recurrent life-threatening hemophagocytic lymphohistiocytosis (HLH) flares. Based on this information, even in the absence of scholarly peer-reviewed articles (unlikely to be available due to the extremely rare nature of this complex condition), trial use of canakinumab is medically necessary and appropriate for this patient.