Chemical or biochemical markers of responders to Rituximab

Topics for discussion

• What are your trigger points?
• What are the checkpoints?
• Factors to help identify who might respond better to B cell therapies.
• How can we identify earlier who might respond better to Rituximab?

Summary

The session was opened by Dr Channa Hewamadduma following which Dr John McConville gave a brief overview of the types of MG, including early-onset with acetylcholine receptor (AChR) antibodies, thymoma-associated MG, and late-onset MG. The role of antibodies, particularly in determining treatment responsiveness, was underscored as crucial to understanding disease progression and management strategies.

B Cells and plasma cells in myasthenia gravis

A key focus was the distinction between B cells and plasma cells. B cells are integral to the pathogenesis of MG, but they do not produce antibodies directly—this is the role of plasma cells, which act as long-lived producers of disease-causing antibodies. The discussion detailed the importance of targeting B cells with therapies like Rituximab, particularly CD20-expressing B cells, while noting that plasma blasts do not express this marker, complicating treatment approaches.

Efficacy of Rituximab in myasthenia gravis

Rituximab, a monoclonal antibody that targets CD20+ B cells, was highlighted for its efficacy in treating MG, particularly in patients with early-onset disease or generalised MG. Clinical data showed that Rituximab significantly reduces the need for steroids and rescue therapies, particularly in late-onset and generalised MG. Dr McConville emphasised the importance of early intervention in maximising the therapeutic benefits of Rituximab.

Challenges in treating refractory myasthenia gravis

The complexities of managing treatment-refractory MG was also discussed.. Despite the promising outcomes of Rituximab, some patients do not respond as expected. The discussion covered the importance of closely monitoring B cell depletion and T cell lymphopenia in these cases. Prolonged B cell depletion may result in long-term immunosuppression, requiring careful patient management.

Practical considerations: preparing patients for Rituximab therapy

Natasha Hoyle outlined the important considerations when preparing patients for rituximab treatment these included:

Pre-Screening and Testing essential tests:

• Hepatitis B serology: Rituximab carries a high risk of hepatitis B reactivation, so screening for current infection, latent infection, or reactivation is crucial.

• Immunoglobulin levels: Patients with low IgG levels are at a higher risk of infectious complications during rituximab treatment.

• Desirable tests include varicella serology, tuberculosis screening, and ECG (if there is a history of cardiac disease).

Hepatitis B Management:

The importance of carefully interpreting hepatitis B serology results was emphasised. Patients with current infection, latent infection, or passive hepatitis B serology (due to previous blood product exposure) require specific management, often involving antiviral prophylaxis throughout the treatment period and for 12 months after the last rituximab infusion.

Vaccination Considerations:

The need to review the patient's vaccination history and ensure they receive appropriate vaccinations before starting rituximab was discussed. Live vaccines should be avoided 4 weeks before and 12 months after the last rituximab infusion. Inactivated vaccines, such as influenza, pneumococcal, and COVID-19 vaccines, are generally safe but may have a suboptimal immune response in immunosuppressed patients.

Comorbidity Assessment:

Assessment of patient's comorbidities and potential contraindications to rituximab include identifying uncontrolled heart disease, active infections, and certain autoimmune conditions (e.g., inflammatory bowel disease, psoriasis) which may warrant caution or alternative treatment options.

Patient Counseling and Consent:

The need for thorough patient counselling and obtaining informed consent was highlighted. Patients should be made aware of the unlicensed use of rituximab for myasthenia gravis, the potential benefits and risks, and the possibility of biosimilar switches during the course of treatment following which Natasha briefly discussed the complexities of funding rituximab, noting that the availability and reimbursement may vary depending on the specific indication and local healthcare policies. In summary,

Q&A Session

The webinar concluded with a lively Q&A session. One notable question concerned the measurement of CD20 and CD19 cells in clinical practice. The speakers explained that, within the NHS, CD19 measurement is more common, providing a broader marker for B cell populations. A further discussion focused on the management of patients exposed to shingles while on Rituximab, with recommendations for immediate medical intervention in such cases.

Conclusion

The webinar provided a comprehensive overview of B cell therapies in MG, with practical advice on using Rituximab effectively. Participants gained valuable insights into the management of both early- and late-onset MG, as well as the challenges posed by treatment-refractory cases. By emphasising careful patient monitoring and preparation, the session reinforced the importance of a personalised approach to therapy in myasthenia gravis.

Action Points:

• Screen patients for hepatitis B, tuberculosis, and varicella immunity before starting Rituximab.

• Counsel patients on the benefits, risks, and off-label use of Rituximab.

• Consider PCP prophylaxis for patients on Rituximab, especially those on high-dose steroids.

• Use standard Rituximab dosing of 500 mg as a single dose for MG patients.

• Monitor B cell levels closely before considering retreatment, particularly in patients with prolonged B cell lymphopenia.