Safety of RTX when used to treat mixed cryoglobulinemic vasculitis
Overall, safety is similar when compared with other treatments. Serum sickness occurs in ∼1% of cases and is usually mild.
One study suggested that the administration of RTX 1 g every 2 weeks is more commonly associated with severe systemic reactions (e.g., exacerbation of vasculitis) than a weekly dosing regimen (375 mg/m 2 × 4 doses).
It is hypothesized that cryoglobulins may form immune complexes with RTX by binding to it in an RF-dependent manner, resulting in an accelerated immune complex-mediated vasculitis.
This phenomenon was dependent on the level of cryoglobulins (high cryoglobulin concentration, low C4) and dose of RTX. Thus, the recommendation was to use a lower dose regimen and to consider plasma exchange prior to administration in patients with high cryoglobulin concentrations (>3%) and/or significant renal insufficiency.
One approach is to carry out plasma exchange every other day for five to seven treatments while placing the patient on high-dose glucocorticoids, subsequently followed by RTX (375 mg/m 2 weekly × 4 doses).
Of note, HCV viral loads may increase when RTX is used as monotherapy in the absence of AV (controversial; conflicting data in the literature, with higher risk potentially among patients with lymphoma receiving a higher cumulative dose of RTX and additional chemotherapeutic agents).
Nonetheless, progressive liver disease has not been described among patients receiving RTX treatment for HCV-associated MC, and it is generally considered safe in this setting alongside proper AV therapy.
