Is it safe to use Remicade (infliximab) and Rituxan (rituximab) infusions together in a patient with End-Stage Renal Disease (ESRD)?

Concurrent Remicade and Rituxan Infusions in ESRD: Safety and Recommendations

Concurrent use of Remicade (infliximab) and Rituxan (rituximab) is not recommended in patients with ESRD, as combining two biologic agents significantly increases the risk of serious infections and other adverse events without providing additional clinical benefit. 1

Why Concurrent Biologics Are Contraindicated

• The American College of Rheumatology explicitly recommends against concurrent treatment with multiple biologic agents in rheumatologic conditions, as this increases the risk of serious infections and adverse events without additional clinical benefit. 1

• Standard treatment protocols require discontinuation of one biologic before initiating another, with an appropriate washout period to minimize adverse event risk. 1

• When switching between biologics like infliximab and rituximab, the current biologic must be discontinued completely before starting the new agent. 1

Specific Considerations for ESRD Patients

Rituximab Safety Profile in ESRD

• Rituximab pharmacokinetics are not affected by ESRD, and no dose adjustments are necessary for renal impairment. 2

• Rituximab has been used successfully in patients with severe renal disease (eGFR ≤20 ml/min/1.73 m²) and ESRD, with acceptable safety profiles when used as monotherapy with glucocorticoids. 3, 4

• In ESRD patients, rituximab can be administered at standard dosing (1000 mg IV every 2 weeks for 2 doses, or 375 mg/m² weekly for 4 weeks) without adjustment. 1, 2

Infection Risk with Combined Immunosuppression

• The combined use of rituximab with additional immunosuppressive agents (such as TNF inhibitors like infliximab) is associated with significantly increased risk of serious infections including bacterial sepsis, tuberculosis, CMV infection, and opportunistic infections. 5

• Patients receiving multiple immunosuppressive agents, particularly those with T-cell-depleting properties combined with B-cell depletion, require intensive infection monitoring. 5

• PJP prophylaxis with trimethoprim-sulfamethoxazole is mandatory during rituximab treatment and for at least 6 months after the last dose, especially when combined with other immunosuppressants. 6

Appropriate Treatment Sequencing

If Switching from Infliximab to Rituximab

• Discontinue infliximab completely before initiating rituximab. 1

• Allow an appropriate washout period (typically 4-8 weeks depending on clinical urgency) before starting rituximab. 1

• Initiate rituximab at standard dosing: 1000 mg IV every 2 weeks for 2 doses, with subsequent courses no sooner than every 16 weeks based on clinical evaluation. 1

Monitoring Requirements During Rituximab Therapy

• Check hepatitis B surface antigen, hepatitis B core antibody, and QuantiFERON test for tuberculosis prior to rituximab administration. 7

• Measure serum IgG levels at baseline and every 6 months during rituximab therapy to detect secondary immunodeficiency. 6

• Monitor CD20 levels to guide treatment duration and response. 7

• Implement PJP prophylaxis with TMP-SMX during treatment and for minimum 6 months after last rituximab dose. 6

Common Pitfalls to Avoid

• Do not assume that concurrent biologics provide additive benefit—they only increase toxicity risk. 1

• Do not initiate rituximab while infliximab is still active in the system without adequate washout. 1

• Do not discontinue PJP prophylaxis prematurely—continue for at least 6 months after the last rituximab dose, and consider longer duration in ESRD patients with ongoing immunosuppression. 6

• Do not overlook baseline immunoglobulin levels—low IgG at baseline predicts higher risk of secondary immunodeficiency and may justify more prolonged prophylaxis. 6

Clinical Decision Algorithm

1. Determine if both biologics are truly necessary: In nearly all cases, only one biologic agent should be used at a time 1

2. If switching from infliximab to rituximab:

   • Discontinue infliximab 1
   • Wait 4-8 weeks for washout 1
   • Complete pre-rituximab screening (hepatitis B, TB, IgG levels) 7, 6
   • Initiate PJP prophylaxis 6
   • Start rituximab at standard dosing 1

3. If patient requires treatment urgency that cannot wait for washout:

   • Consider alternative non-biologic immunosuppression during transition period
   • Consult with nephrology and rheumatology/gastroenterology for risk-benefit assessment
   • Implement intensive infection monitoring protocols 5

4. For ESRD-specific management:

   • No rituximab dose adjustment needed 2
   • Ensure adequate dialysis clearance for supportive medications
   • Monitor for infection complications more intensively given baseline immunocompromised state from uremia 5