Diagnosis: Cancer Associated Retinopathy
Treatment: IVIG J1459 (Privigen)
The insurer denied the IVIG J1459 (Privigen).
The denial is overturned.

The patient is a male with cancer-associated retinopathy (CAR), for whom coverage of IVIG (intravenous immunoglobulin) J1459 is the subject of review. Reportedly, the patient received IVIG during a hospital stay and saw significant improvement. Coverage was previously denied as such treatment is not FDA (United States Food and Drug Administration)-approved.

A provider note documents the patient having received chemotherapy for lung cancer. As a result of this cancer and treatment, the patient developed rapid and progressive vision loss. He was subsequently diagnosed with CAR, for which IVIG was recommended after having previously been treated and having failed steroid therapy. The provider states that this condition is very rare, which is why there is limited data in the literature. The patient was admitted and received IVIG and reportedly experienced improved vision after one dose. Therefore, the provider believes it should be continued. Monthly dosing of 0.5g/kg (grams per kilogram) is recommended. An alternative would be plasmapheresis or azathioprine, although evidence to support such use is less impressive.

Yes, the proposed IVIG treatment is established as medically necessary in this case.

CAR is a member of a spectrum of disease called autoimmune retinopathy. Autoimmune retinopathy is broadly separated into neoplastic and nonneoplastic. CAR is a subtype of paraneoplastic syndrome and was first described by Sawyer, et al in 1976 with three cancer patients with blindness caused by diffuse retinal degeneration. In CAR, retinal degeneration occurs in the presence of auto-antibodies that cross-react with tumor-tissue and retinal-tissue antigens which are recognized as foreign. In many instances, visual loss from CAR precedes the diagnosis of cancer.

There are no guidelines for the treatment of CAR, but a high index of suspicion with early implementation of treatment may lower the risk of irreversible vision loss. Long-term systemic immunosuppression is the main therapy for CAR, with variable results. Local corticosteroid, systematic immunosuppressive medications (high-dose corticosteroid, cyclosporin, azathioprine, alemtuzumab), IVIG, plasmapheresis, and a combination of these treatments have been utilized. Rituximab is starting to be used more frequently with improvement noted in case series and case reports of CAR and autoimmune retinopathy. A retrospective case series evaluating rituximab with concomitant immunosuppressive agents (mycophenolate, cyclophosphamide, IVIG, bortezomib, topical steroids) in 16 neoplastic and non-neoplastic autoimmune retinopathy patients (six CAR patients) demonstrated 77% of eyes achieving stable or improved vision.

Support in the peer reviewed medical literature for the safety and effectiveness of IVIG in the treatment of CAR is limited. Ramos-Ruperto recently reported and reviewed a case of CAR treated with IVIG. A woman, former smoker, presented with bilateral subacute decreased visual acuity with one month of evolution, without other symptoms. Clinical examination revealed retinal atrophy and a mild vitritis component. Treatment with corticosteroid and IVIG was initiated empirically with the stabilization of visual loss. Anti-recoverin antibodies tested positive and a small cell lung carcinoma was diagnosed. In a review of the literature, the authors found that only 12 cases of patients treated with intravenous immunoglobulins have been reported. The authors concluded that the early use of IVIG could contribute to an improvement and/or stabilization of visual symptoms in this patient group, due to its rapid effect and lower profile of adverse effects when administered with chemotherapy.

There is currently no proven treatment for the patient's rare condition. However, there is some support in the medical literature for the use of IVIG. The patient has already tried and failed steroids and shown positive response to initial treatment with IVIG. Therefore, IVIG is established as medically necessary and appropriate per standard of care.

The health plan denied the treatment based solely on the fact that IVIG is not FDA-approved for this patient's indication. However, this patient has a rare condition for which there is no FDA-approved treatment. There is no documentation that the plan further evaluated the support for the use of IVIG in this scenario.