Appeal type: Experimental/Investigational
Decision: Overturned

Reviewer #3:

Diagnosis: Autoinflammatory syndrome

Treatment: Actemra

The insurer denied coverage for Actemra. The denial is reversed.

This patient was then a male child with autoinflammatory syndrome who presented with recurrent febrile episodes starting at an infant. The patient had fever for several days each month along with headaches, abdominal pain and bowel disturbance. The patient's clinical workup and genetic studies ruled Crohn's disease, familial Mediterranean fever (FMF), Tumor necrosis factor receptor-associated periodic syndrome (TRAPS), Mevalonate Kinase Deficiency (MKD) also known as Hyper IgD Syndrome (HIDS), Cryopyrin-Associated Autoinflammatory Syndromes (CAPS) and Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis (PFAPA), hematologic or infectious etiology. 

The patient was evaluated at the National Institute of Health (NIH). The patient's genetic testing revealed that the patient carried a D324Y mutation in RIPK1, which rendered the protein unable to be cleaved, and cannot be deactivated, resulting in his autoinflammatory syndrome. At this point, the patient had not responded to multiple drugs including anakinra, colchicine, methotrexate, Remicade, and Enbrel. The patient was then initiated on intravenous (IV) tocilizumab (Actemra) 8 mg/kg infusion every 4 weeks. The patient's symptoms clinically improved after 4 infusions. The patient's rheumatologist wished to continue treatment with this medication and requested prior authorization for therapy with subcutaneous Actemra 162 mg weekly.

As to date, there is very limited scientific evidence in peer-reviewed literature. The literature is limited to very small studies or case studies. Autoinflammatory syndrome is a rare disease, for which there are different subtypes with genetic mutations/deletions, though there are some subtypes that genetic mutation/deletion is not always present in an individual. Per a specified note the patient was found to have a D324Y mutation on RIP kinase1 gene, which is the cause of this patient's autoinflammatory condition. Literature review shows in terms of autoinflammatory syndromes resistant to standard, FDA-approved therapy that Actemra (tocilizumab) can result in symptom improvement for refractory cases.

In this case, the patient had been treated with anakinra, colchicine, methotrexate, Remicade, and Enbrel. Only with Remicade and methotrexate was there some improvement, so treatment was changed to tocilizumab by NIH. After a few treatments with tocilizumab, the patient had shown significant clinical improvement, with fewer fever episodes, less abdominal pain, headaches, and even begun to gain some weight. 

Per the records by the treating providers, the patient has experienced clinical improvement with the use of this medication. The National Institutes of Health (NIH) have been following this patient's treatment. The patient had failed all standard treatments, and there was no other FDA approved options for treatment. Treatment with Actemra was the last course of action. Though Acemra is not FDA-approved for treating this patient's specific condition, this patient's rare and difficult to treat condition was responding well to this treatment. Thus, this patient is a good candidate for Acemra use as an off-label use for his rare disease. The literature review support that this requested medication, Actemra is likely to be more beneficial than any of the standard treatments for this patient.
The carrier's denial of Actemra should be reversed.