Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Multiple Sclerosis; Vulvovaginal Ulcerations.
Treatment: Gamunex Injection, Pre-service.
The insurer denied the Gamunex Injection, Pre-service.
The denial is overturned. 

The patient is a woman who developed vaginal ulcerations due to pyoderma gangrenosum as a result of rituximab therapy for multiple sclerosis. The patient is disabled because of the alterations. She has complete detachment of the urethra from the pelvic floor. She has missed work and is unable to participate in family functions. She has improved with prednisone, cyclosporine, and two infusions of IVIG (intravenous immunoglobulin). Her dermatologist is requesting approval for outpatient infusions to avoid hospital admissions for IVIG (intravenous immunoglobulin).

Yes, the health plan should cover the treatment with Gamunex.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by rapidly progressing necrolytic ulceration of the skin. Proper treatment is crucial since it can result in devastating consequences. First-line treatments include systemic corticosteroids or cyclosporine. However, no standardized treatment regimens for refractory cases exist, and treatment outcomes are affected by underlying conditions.

There is evidence supporting a potential role for intravenous immunoglobulin (IVIG) as adjuvant therapy for treatment-resistant cases. IVIG (intravenous immunoglobulin) is typically given in divided doses over the course of two to five days, repeated monthly.

Efficacy data for IVIG (intravenous immunoglobulin) for PG (pyoderma gangrenosum) are limited. A systematic review of cases and case series documenting treatment of refractory PG (pyoderma gangrenosum) with IVIG (intravenous immunoglobulin) (often in conjunction with systemic glucocorticoids) found complete responses in 26 of 49 patients (53 percent) and complete or partial responses in 43 of 49 patients (88 percent). The mean time to initial response was 3.5 weeks, and patients were treated for an average of 5.9 months. Limitations of the review included potential publication bias given that most data were derived from case reports and a paucity of long-term, follow-up data in the included patients. Moreover, failures to respond to retreatment with IVIG (intravenous immunoglobulin) upon disease relapse have occurred. Well-designed prospective trials are necessary to clarify the efficacy of IVIG (intravenous immunoglobulin) for PG (pyoderma gangrenosum).

Immune globulin derived from the plasma of paid and volunteer donors is used in the treatment of an array of disorders, including primary and secondary immune deficiency states and a variety of autoimmune and inflammatory disorders. PG (pyoderma gangrenosum) is not an FDA (Food and Drug Administration) approved indication for use of IVIG (intravenous immunoglobulin). However, it is an accepted off label use, as evidenced by UpToDate. Since there are no standard, approved therapies for the treatment of pyoderma gangrenosum, every treatment is going to be an off-label use. Therefore, since the patient has already improved with a combination of systemic steroids, cyclosporine, and IVIG (intravenous immunoglobulin), continued therapy is medically appropriate.

Yes, the treatment with Gamunex is likely to be more beneficial.

As a result of the paucity of data on interventions for PG (pyoderma gangrenosum), definitive guidelines for patient management are lacking. The approach to the treatment of PG (pyoderma gangrenosum) is primarily guided by small uncontrolled studies and clinical experience. In general, patients are managed with a combination of topical and/or systemic therapies that suppress the inflammatory process and wound care measures that optimize the environment for wound healing. Although initial signs of improvement may be evident within days of the start of treatment, weeks to months are often required to achieve complete ulcer healing. Since the patient has already improved with a combination of systemic steroids, cyclosporine, and IVIG (intravenous immunoglobulin), continued therapy is medically appropriate.