Management of Rituximab in Frequently Relapsing Nephrotic Syndrome
Steroids should be used to achieve remission before initiating rituximab in cases of frequently relapsing nephrotic syndrome. 1
Initial Management of Relapse
- Treat the current relapse with oral prednisone at 60 mg/m² per day (maximum 60 mg) as a single daily dose until remission (urine dipstick trace/negative for at least 3 consecutive days) 1
- Once remission is achieved, decrease to 40 mg/m² per day (maximum 40 mg) on alternate days for 1 week, then taper by 10 mg/m² per week to complete a total of 4 weeks of treatment 1
- For frequently relapsing/steroid-dependent nephrotic syndrome, maintenance alternate-day prednisone should be continued for at least 3 months, with most clinicians choosing the lowest dose to maintain remission 1
Timing of Rituximab Administration
- Rituximab should be initiated only after achieving remission with corticosteroids 1, 2
- This sequencing is similar to the recommendation for cyclophosphamide, which should not be started until the child has achieved remission with corticosteroids 1
- Administering rituximab during active disease (before remission) may reduce its effectiveness and increase the risk of complications 2
Rituximab Protocol
- Administer rituximab as a single intravenous infusion of 375 mg/m² 1, 2
- Premedicate with acetaminophen and an antihistamine to prevent infusion reactions 2
- Consider a second dose after 1-3 months if B-cell recovery occurs with early signs of relapse 2, 3
- Monitor CD19/CD20 B-cell counts every 1-3 months to assess for B-cell recovery and potential need for additional doses 2
Evidence Supporting This Approach
- In clinical studies, rituximab has demonstrated significant efficacy when administered during remission, with 87% of children remaining in remission at 1 year and 53% at 4 years following a single infusion 3
- The KDIGO 2021 guidelines recommend rituximab as an appropriate steroid-sparing agent for children with steroid-dependent nephrotic syndrome 1, 2
- Rituximab has shown effectiveness in both frequently relapsing and steroid-dependent forms of nephrotic syndrome 2
Common Pitfalls and Caveats
- Failure to achieve complete remission before administering rituximab may reduce its effectiveness 1, 2
- Hepatitis B surface antigen, hepatitis core antibody, and QuantiFERON test for tuberculosis must be checked prior to rituximab administration 1
- Monitoring IgG levels both before and after rituximab therapy may allow for earlier identification of risk for developing significant infection 1
- Serum sickness can occur following rituximab administration and should be monitored for 4
Alternative Approaches if Rituximab is Not Available
- Consider other steroid-sparing agents such as levamisole (first-line if available), cyclophosphamide, calcineurin inhibitors, or mycophenolate mofetil 1, 2
- These agents should also be initiated only after achieving remission with corticosteroids 1
By following this approach of achieving remission with steroids before administering rituximab, you maximize the chances of long-term remission while minimizing the risks associated with both medications.