Is it safe to use Rituxan (rituximab) and Tavneos (avacopan) together?

Combination Therapy with Rituximab and Tavneos (Avacopan)

Yes, Rituximab (Rituxan) and Tavneos (avacopan) can be safely used together, and this combination is specifically recommended by KDIGO 2024 guidelines for ANCA-associated vasculitis as an alternative to glucocorticoid-based regimens. 1

Evidence-Based Recommendation

The combination of rituximab plus avacopan (without glucocorticoids) is an established treatment option for induction of remission in ANCA-associated vasculitis, offering comparable efficacy to traditional glucocorticoid-containing regimens while potentially reducing steroid-related toxicity. 1

Guideline Support for Combined Use

• KDIGO 2024 explicitly recommends rituximab combined with either glucocorticoid taper OR avacopan as first-line induction therapy for ANCA-associated vasculitis 1
• The guideline presents this as: "Rituximab + (glucocorticoid taper or avacopan)" indicating these are interchangeable partners with rituximab 1
• Avacopan serves as a glucocorticoid-sparing alternative when combined with either rituximab or cyclophosphamide for remission induction 1

Clinical Context and Patient Selection

Patients who benefit most from rituximab-avacopan combination (avoiding glucocorticoids) include those at high risk for steroid toxicity: 1

• Patients with increased infection risk 1
• Those with pre-existing diabetes mellitus 1
• Patients with psychiatric disorders 1
• Those with osteoporosis 1
• Patients with lower kidney function (eGFR <20 ml/min per 1.73 m²), who may experience increased recovery of kidney function with this combination 1

Dosing Specifications

Rituximab dosing options when combined with avacopan: 1

• 375 mg/m² weekly for 4 weeks 1
• OR 1 g at weeks 0 and 2 1

Avacopan dosing: 1

• 30 mg twice daily as alternative to glucocorticoids, in combination with rituximab or cyclophosphamide induction 1

Safety Monitoring Requirements

When using rituximab with avacopan, implement the following monitoring protocol: 1, 2

• Measure baseline IgG levels before rituximab initiation, as low baseline IgG (<3 g/l) predicts greater risk of secondary immunodeficiency 1
• Monitor immunoglobulin levels (IgG, IgM, IgA) every 6 months during rituximab therapy 1, 2
• Obtain hepatitis B and C screening prior to administration 2
• Perform latent tuberculosis screening before starting rituximab 2
• Monitor complete blood count with differential at baseline and 2-4 month intervals 2

Infection Prophylaxis

Pneumocystis pneumonia prophylaxis is mandatory: 1

• Use low-dose trimethoprim-sulfamethoxazole (or alternative) for 6 months following rituximab induction 1
• Consider longer-term prophylaxis for patients receiving repeated rituximab infusions, those with structural lung disease, or those requiring ongoing immunosuppressive therapy 1

Important Caveats and Limitations

Financial considerations and lack of long-term data currently limit widespread applicability of avacopan: 1

• The cost of avacopan may be prohibitive in some healthcare settings 1
• Long-term safety data beyond initial clinical trials remain limited 1

In severe kidney disease (serum creatinine >4 mg/dl or >354 mmol/l), data supporting rituximab-avacopan without glucocorticoids are limited: 1

• No patients with SCr >4 mg/dl were included in the RAVE trial evaluating rituximab 1
• In this setting, consider adding cyclophosphamide to rituximab, or using cyclophosphamide with glucocorticoids as preferred alternatives 1

Real-World Clinical Experience

A case report demonstrates successful use of rituximab and avacopan without glucocorticoids in a 78-year-old woman with granulomatosis with polyangiitis, resulting in prompt resolution of fever, thigh pain, improved auditory acuity, and lung nodule improvement, with no adverse effects from either agent 3

Infection Risk Considerations

While rituximab carries infection risk, particularly with prolonged B-cell depletion, the combination with avacopan (avoiding glucocorticoids) may reduce overall infection burden compared to traditional steroid-based regimens: 4, 5

• Pre-existing hypogammaglobulinemia increases risk of serious infections after rituximab 4
• Concomitant use of additional immunosuppressive agents (like cyclophosphamide) increases hypogammaglobulinemia risk 4
• The avacopan-rituximab combination avoids the immunosuppressive effects of high-dose glucocorticoids 1