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OP0212 Very Long-Term Effects of the “4 Plus 2 Infusion Protocol” of Rituximab Alone in Patients with HCV-Associated Mixed Cryoglobulinemia with Diffuse Membranoproliferative Glomerulonephritis, Severe Polyneuropathy and Necrotic Ulcers of Skin
  1. D. Roccatello1,
  2. S. Sciascia1,
  3. S. Baldovino1,
  4. D. Rossi1
  1. 1Department Of Rare And Immunologic Diseases, G. Bosco Hospital And University Of Turin, TOrino, Italy


Background Mixed cryoglobulinemia syndrome (MCs) is a systemic vasculitis characterized by multiple organ involvement due to the vascular deposition of IgMk/IgG cryoglobulins. B cells expansion usually triggered by HCV infection plays a central role in MCs.

Objectives to evaluate the long term effects of B-cells depletion in MCs

Methods Twenty seven patients, (mean age 60.2 [range 35-78] years, HCV infection in 96% of cases) with symptomatic type-II MCs with systemic manifestations, including renal involvement (diffuse membranoproliferative glomerulonephritis in 15 cases), peripheral neuropathy (26 cases) and large skin ulcers (9 case, in 7 necrotizing) were considered eligible for Rituximab (RTX) therapy. RTX was administered at a dose of 375 mg/m2 on days 1, 8, 15 and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms, laboratory parameters and electromyographic indices for a very long term follow-up (mean 54.3 months [12-96])

Results Complete remission of pre-treatment active manifestations was observed in all the cases of skin purpuric lesions and non-healing vasculitic leg ulcers, and in 80% of cases of peripheral neuropathy. A significant improvement in the clinical neuropathy disability score was observed. Electromyography revealed that the amplitude of compound motor action potential had increased. Cryoglobulinemic glomerulonephritis, observed in 15 patients, significantly improved during the follow-up starting from the second month after RTX (serum creatinine from 2.2±1.9SD to 1.6±1.2SD mg/dl, p≤.05; 24-hour proteinuria from 2.3±2.1SD to 0.9±1.9SD g/24h, p≤.05). Significant improvement of serological hallmarks, such as cryocrit and low complement C4, were also detected (p≤.05). The safety of RTX was confirmed by the absence of side effects recorded during the mean 54-month follow-up. Re-induction was performed in 9 relapsed cases (after a mean of 31.1 months, range 12-54) with resolutive beneficial effects.

Conclusions In this open prospective study, the “4 plus 2 infusion protocol” of RTX appeared to be very effective and safe in the treatment of patients with MCs-associated membranoproliferative nephritis, polyneuropathy and severe skin involvement.

Disclosure of Interest None Declared

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