Use of AV agents and RTX in the treatment of HCV associated mixed cryoglobulinemic vasculitis
AV agents should be considered in all patients with HCV-associated MC. Historically, interferon-based regimens demonstrated response rates of 30% to 80% in MC, but use was commonly limited due to contraindications, side effects (interferon-α may exacerbate vasculitis manifestations), and slow onset of action. Direct acting antivirals (DAA), however, have transformed therapeutic outcomes in patients with HCV-associated MC. Treatment with DAA has shown an immunologic response in patients, with decreases in cryocrit in up to 80% of those treated, and clinical response in 91% of patients according to the Birmingham Vasculitis Activity Score. It is of interest to note that some patients may experience continued episodes of vasculitis despite viral clearance.
RTX has demonstrated good efficacy in treating mixed cryoglobulinemic vasculitis (clinical response in 80%) and should be considered in all patients with moderate-to-severe disease. Its use in combination with AV agents has demonstrated superiority over either agent used alone. RTX monotherapy has also been shown to be more efficacious than standard-of-care immunosuppression (high-dose steroids, azathioprine, cyclophosphamide, plasma exchange, or a combination of these). Typical response rates with combination therapy are 70% to 80%, with most patients experiencing complete clinical response. Addition of RTX to AV agents typically results in a more rapid clinical response and improved renal outcome than AVs alone. Improvement may be seen as early as 1 month, but typically occurs within 3 to 6 months. Clinical response rates are commonly higher than immunologic and virologic response, indicating that viral and immunologic responses may not be necessary for clinical efficacy.
There is no consensus regarding how RTX and AVs should be administered in patients presenting with HCV-associated MC. Patients with severe end-organ damage from vasculitis should be treated with immunomodulation first, followed by DAA after clinical stabilization ( Fig. 31.2 ). Studies have evaluated dosing RTX 1 g every 2 weeks (2 doses) and 375 mg/m 2 weekly for 4 weeks, and both are effective.
