The case for cost-effectively treating cryoglobulinemic vasculitis with interferon-free anti-hepatitis C virus therapy.

.Mixed cryoglobulinemia (MC) vasculitis affects approximately 5% of individuals with chronic hepatitis C virus (HCV) infection and ranges from mild to life-threatening.1 Sustained virological response leads to remission of vasculitis and reduced mortality, but the response rate to interferon-based regimens is low for frequent intolerance and ineligibility.1 Interferon-ineligible/intolerant/nonresponder patients with severe organ damage require salvage treatments with rituximab (RTX) or plasma exchange; however, these treatments are expensive and provide only temporary benefit.1,2 Both the American Association for the Study of Liver Diseases (http://www.hcvguidelines.org/full-report/when-and-whom-initiatehcv- therapy) and the European Association for the Study of the Liver (http://www.easl.eu/_newsroom/latest-news/easl-recommendations- on-treatment-of-hepatitis-c-2014) recommend prioritizing anti-HCV treatment in patients with MC vasculitis, but the impact of the severity of vasculitis on indication for early treatment is not thoroughly addressed. We performed a retrospective chart review of 58 patients with HCV-associated MC vasculitis followed at our institution (Supporting Methods). Interferon-based therapy led to sustained virological response in 11 patients (19%) (Supporting Fig. S1). Vasculitis was stratified into mild/moderate (purpura, peripheral neuropathy) and severe (nephropathy, chronic skin ulcers). Thirty interferon-ineligible/intolerant/nonresponder patients with chronic hepatitis, stable through follow-up, were selected; eight of them had severe vasculitis and 22 mild/moderate vasculitis (Supporting Fig. S1). The healthcare history, costs, and outcomes were compared in these two groups (Table 1); only hospitalizations and treatments related to complications of vasculitis were considered. Patients with severe vasculitis stayed in hospital a mean of 16.59 days/year and were all treated with RTX, plasma exchange, or both. Two of eight patients with severe vasculitis died from its complications, one from intestinal vasculitis and one from endstage renal disease and systemic infection resulting from infected skin ulcers. Patients with mild/moderate vasculitis stayed in hospital 0.66 days/year; only two of 22 were treated with RTX, and none died. Thus, healthcare cost overall and risk of death were higher in patients with severe MC compared to those with mild/moderate disease. Furthermore, there did not appear to be an association of use of either plasma exchange or RTX with cost (Supporting Table S1), which may have been related more to severity of illness than to response to treatment. Hagan et al.3 surmise a 12-week treatment with sofosbuvir/simeprevir, at a drug cost of $150,000, as the state-of-the-art, most costeffective therapy for interferon-ineligible/intolerant HCV-infected individuals. Given the relatively high cost of care and the poor response/ high risk of death in patients with severe MC, prioritization of these patients for treatment with interferon-free therapy should be considered; and studies to determine tolerability and efficacy are warranted.