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Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study
Dario Roccatello1, Savino Sciascia, Simone Baldovino
1Department of Rare, Immunologic, Hematologic and Immunohematologic Diseases, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital, Turin, Italy.
Background:
In a prospective, single-center open study, we evaluated the very long-term effects of rituximab (RTX) administered to patients with severe mixed cryoglobulinemia (MC).
Methods:
RTX was administered to 31 patients with MC (type II in 29 cases and type III in 2) with diffuse membranoproliferative glomerulonephritis (16 cases), peripheral neuropathy (26) and large skin ulcers (7). All but 4 patients had serum anti-hepatitis C virus antibodies. RTX was administered at a dose of 375 mg/m2, according to a '4 + 2' protocol (days 1, 8, 15 and 22 plus 1 dose 1 and 2 months later). No other immunosuppressive drugs were added. Response was evaluated over a very long-term follow-up (mean 72.47 months, range 30-148).
Results:
Complete remission of pretreatment active manifestations was observed in all cases of purpuric lesions and non-healing vasculitic ulcers, and in 80% of the peripheral neuropathies. Cryoglobulinemic nephropathy significantly improved during follow-up, starting from the 2nd month after RTX (serum creatinine from 2.1 ± 1.7 to 1.5 ± 1.6 mg/dl, p ≤ 0.05; 24-hour proteinuria from 2.3 ± 2.1 to 0.9 ± 1.9 g/24 h, p ≤ 0.05). Improvement of cryoglobulinemic serological hallmarks, such as cryocrit and low complement C4, were observed. No clinically relevant side effects were recorded. Re-induction with RTX was carried out in 9 relapsed patients after a mean of 31.1 months (12-54), again with beneficial effects. The survival rate was 75% at 6 years and the probability of remaining symptom-free for 10 years without any therapy was of about 60% after a single '4 + 2' infusion cycle, while the probability of living symptom-free 5 years after relapsing was 80% if given the same treatment.
Conclusion:
In this open, prospective study, RTX appeared to be very effective and safe in the treatment of the most severe cases of MC.
Insights
Rituximab (RTX) offers significant long-term benefits for severe mixed cryoglobulinemia (MC) patients, effectively treating manifestations like neuropathy and ulcers. This treatment demonstrates sustained efficacy and safety, improving patient outcomes over many years.
Area of Science:
- Immunology
- Nephrology
- Rheumatology
Background:
- Severe mixed cryoglobulinemia (MC) presents significant challenges, often involving kidney and nerve damage.
- Patients with MC frequently exhibit manifestations like peripheral neuropathy, skin ulcers, and glomerulonephritis.
- Hepatitis C virus (HCV) is a common comorbidity in MC patients.
Purpose of the Study:
- To evaluate the very long-term effects of rituximab (RTX) in patients with severe mixed cryoglobulinemia (MC).
- To assess the safety and efficacy of RTX in managing MC-related complications.
- To determine the sustained impact of RTX on disease activity and patient survival.
Main Methods:
- A prospective, single-center open study involving 31 patients with severe MC.
- RTX administered at 375 mg/m2 using a '4 + 2' protocol, without other immunosuppressants.
- Long-term follow-up averaging 72.47 months (range 30-148 months) to assess treatment outcomes.
Main Results:
- Complete remission was observed in purpuric lesions, ulcers, and 80% of peripheral neuropathies.
- Significant improvement in cryoglobulinemic nephropathy, with reduced serum creatinine and proteinuria.
- Positive serological changes, including cryocrit and C4 levels, with no major side effects reported.
- High survival rates (75% at 6 years) and sustained symptom-free periods observed.
Conclusions:
- Rituximab (RTX) is highly effective and safe for treating severe mixed cryoglobulinemia (MC).
- The '4 + 2' RTX protocol provides very long-term benefits and symptom control.
- RTX represents a valuable therapeutic option for severe MC, improving quality of life and survival.
