What Side Effects Do Nucala and Rituxan Cause in EGPA?

When treating Eosinophilic Granulomatosis with Polyangiitis (EGPA), mepolizumab (Nucala) and rituximab (Rituxan) are two biologic therapies your care team might consider. These medications are not interchangeable; they are used for different stages and severities of EGPA ^[1]. Mepolizumab is typically used for non-severe or relapsing disease to help reduce asthma symptoms and the need for corticosteroids ^[2]. Rituximab is generally reserved for severe, organ-threatening vasculitis, often as part of induction therapy (the initial phase of treatment meant to rapidly control severe inflammation) ^[3].

Because they work on entirely different parts of the immune system, their side effect profiles differ significantly.

Mepolizumab (Nucala): What to Expect

Mepolizumab is given as a subcutaneous (under the skin) injection, often every 4 weeks for EGPA. It specifically targets an immune protein called IL-5 to reduce the number of eosinophils (a type of white blood cell) ^[4].

• Injection Site Reactions: The most common side effect is a reaction where the shot was given, causing temporary redness, swelling, or pain ^[5].
• Allergic Reactions (Hypersensitivity): Although rare, serious allergic reactions, including anaphylaxis, can occur. Seek emergency help if you develop hives, facial or throat swelling, wheezing, dizziness, or trouble breathing after an injection ^{[2] [5]}.
• General Symptoms: Patients may experience headaches, back pain, or fatigue. While clinical trials showed a safety profile roughly similar to placebo, serious reactions are still possible and require monitoring ^{[2] [6]}.
• Parasitic Worm (Helminth) Infections: Eosinophils help your body fight off parasites. If you have a known parasitic infection, it should be treated before starting mepolizumab ^[7]. If you develop an infection during treatment that does not respond to standard anti-parasite medication, your doctor may need to pause your Nucala ^[7].

Rituximab (Rituxan): What to Expect

Rituximab is given via intravenous (IV) infusion. It depletes B-cells, a different type of white blood cell that produces antibodies and drives inflammation ^[8]. Because it more broadly affects antibody production, it requires closer monitoring for immune-related risks.

• Infusion Reactions: Reactions during the IV infusion are common, particularly the first time ^[9]. Alert your infusion nurse immediately if you experience itching, flushing, throat tightness, chest pain, wheezing, or fever during your treatment ^[10]. Severe narrowing of the airways (bronchospasm) can occur, but staff will monitor you closely to stop or slow the infusion if needed ^[11].
• Increased Risk of Infection: B-cell depletion makes you more susceptible to bacterial, viral, fungal, and opportunistic infections ^{[3] [12]}. This risk can persist for months. Because you may also be on high doses of corticosteroids, your doctor might prescribe an antibiotic (like trimethoprim-sulfamethoxazole) to prevent specific opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP) ^[3].
• Changes to Blood Counts and Antibodies: Rituximab can cause late-onset neutropenia (a drop in infection-fighting white blood cells) weeks or months after treatment ^[13]. It can also lead to hypogammaglobulinemia (a long-term decrease in the antibodies your body uses to prevent infections) ^{[14] [15]}.
• Hepatitis B Reactivation: Rituximab can cause dormant Hepatitis B to reactivate, leading to severe liver damage ^[16]. Your doctor will run specific blood tests (HBsAg, anti-HBc, and anti-HBs) before you start ^[17]. If you have evidence of a past infection, you may still be able to receive rituximab, but you will need antiviral medication and close monitoring by a specialist ^[16].
• Rare Neurological Risks: In extremely rare cases, rituximab has been linked to Progressive Multifocal Leukoencephalopathy (PML), a potentially fatal viral brain infection ^{[18] [19]}. Seek prompt medical evaluation if you develop progressive, new, or worsening weakness, clumsiness, balance problems, speech or memory changes, or confusion ^[18].

Protecting Yourself: Proactive Steps

Reading about rare complications can be frightening, but medical monitoring, screening, and scheduled blood tests are specifically designed to reduce these risks.

Monitor and Report Symptoms

• Infections: Do not try to “tough out” an illness. Call your care team promptly if you have a fever, new cough, painful urination, or unusual weakness ^[3].
• Hygiene: Wash your hands frequently and avoid close contact with noticeably sick individuals.
• Medication Changes: Never pause or reduce your corticosteroid (prednisone) dose without your doctor’s explicit instructions, even if you feel well or are worried about side effects ^[20].

Plan Your Vaccinations

Because rituximab suppresses the B-cells that respond to vaccines, you should get necessary vaccines before starting treatment ^[21].

• Non-Live Vaccines: These are generally safe but may be less effective if given during or shortly after rituximab treatment. The recommended shingles (zoster) vaccine is a non-live recombinant vaccine and should be discussed before starting ^[21].
• Live Vaccines: Live vaccines should generally be avoided while your immune system is suppressed by B-cell therapies ^[22]. Always check with your rheumatologist before receiving any new vaccination.

Keep Up with Lab Work

Your care team will periodically check your complete blood count (CBC) and immunoglobulin (antibody) levels ^{[16] [14]}. These routine checks help identify late-onset neutropenia or low antibodies before they lead to a severe infection ^[15].