Is there a PDA for aHUS treatment continuation?

A PDA or patient decision aid is becoming an important part of the increasing shared decision making by patients and doctors.

How do patients prepare themselves for a discussion on the issue of discontinuing complement inhibitor treatment for aHUS.

They could ask the internet. Such searches these days are powered by artificial intelligence tools.

What would a commonly used AI tool say in response to a question about “is there a patient decision aid for discontinuing complement inhibitor treatment?”.

This is what it would say…

“Yes, there is a proposed patient decision aid for the discontinuation of complement inhibitor treatment, specifically for patients with atypical hemolytic uremic syndrome (aHUS), developed by the aHUS Alliance Global Action. This model, published on July 16, 2024, and further discussed on October 22, 2024, is designed from the patient’s perspective to facilitate informed decision-making in collaboration with clinicians. Below, I provide details on this decision aid, its purpose, structure, and limitations, based on available information from the provided web results.

1. Overview of the Patient Decision Aid

Purpose: The decision aid aims to empower aHUS patients to make informed choices about whether to discontinue complement inhibitor treatments, such as eculizumab or ravulizumab, which target the complement system (e.g., C5 inhibitors) to manage aHUS. It addresses the absence of standardized clinical guidelines for discontinuation and helps patients articulate their stance in discussions with clinicians.
Context: Discontinuing complement inhibitors is a significant decision due to the risk of aHUS relapse, which can lead to severe complications like kidney failure. The model balances the chances of relapse with strategies to mitigate harm, emphasizing patient safety and informed consent.
Developer: The aHUS Alliance Global Action, a patient advocacy group, created this model based on global research, including academic articles, clinical studies, and patient feedback. It is not an official clinical guideline but a tool to foster doctor-patient dialogue.

2. Structure and Components of the Decision Aid

The decision aid is a structured model that incorporates evidence-based factors and patient-centric considerations. Key elements include:

Relapse Risk Assessment:
The model also includes a remission/relapse risk matrix to evaluate the likelihood of aHUS recurrence after discontinuation. This is informed by studies showing that ~20-30% of patients relapse after stopping eculizumab, with higher risks for those with specific genetic variants (e.g., CFH, C3, MCP/CD46).
Genetic factors are critical, as pathogenic variants in complement genes (e.g., CFH, MCP) increase relapse risk (e.g., 40% relapse rate in patients with CFH/MCP variants vs. 0% in those without variants).
Clinical factors, such as age, baseline renal function, prior kidney transplant, and ability to tolerate a recurrent thrombotic microangiopathy (TMA) event, are also considered.
Safety and Monitoring Protocols:
The model emphasizes safe discontinuation with rigorous monitoring to detect relapse early. Protocols include:
- Regular urine dipstick tests (once or twice weekly) for proteinuria and hematuria, performed at home.
- Blood tests (weekly for 1 month, biweekly for 3 months, monthly thereafter) to monitor serum creatinine, hemoglobin, platelet count, lactate dehydrogenase, haptoglobin, and proteinuria-to-creatinuria ratio.
- Rapid reinitiation of eculizumab (within 24-48 hours) if relapse is suspected.
Patients are educated on the need to consult physicians immediately for signs of relapse (e.g., fatigue, dark urine, swelling).
Patient-Centered Decision Framework:
The model encourages patients to gather evidence on predictive factors (e.g., genetic profile, treatment duration) and assess their comfort with risks.
It supports dialogue with clinicians, helping patients articulate preferences and concerns, such as quality of life, infection risks from long-term treatment, or cost savings from discontinuation.
Feedback from users indicates the model has been used to initiate discussions with clinicians, with some patients showing it to doctors as a basis for decision-making.

3. Evidence Supporting the Decision Aid

The model draws on extensive research, including:

Clinical Studies:
The French “StopEcu” study (2020) reported 13/55 patients relapsed after eculizumab discontinuation, with full phenotype/genotype data guiding predictive factors.
A 2021 study showed eculizumab discontinuation was safe in 80.6% of 31 aHUS patients, with a 20% relapse rate, lower (11.1%) with clinician-directed monitoring vs. 42.8% with nonadherence.
A 2023 study on complement gene variants found that CFH, C3, or MCP/CD46 variants discourage discontinuation due to high relapse risk, while low-risk patients can safely stop with monitoring.
Global Action’s Work:
The model synthesizes 18 articles on discontinuation, including the Acosta group’s finding that ~70% of aHUS patients remain in remission post-discontinuation.
It incorporates insights from qualitative studies, such as interviews with 10 experts, showing converging doctor and patient perceptions on discontinuation.

4. Feedback and Utility

Patient Feedback: Over three months (July-October 2024), the model received positive feedback for supporting discontinuation decisions and fostering clinician dialogue. No suggestions for improvement were reported, indicating its perceived utility.
Limitations:
The model is patient-focused, not a clinical guideline, and lacks universal adoption due to advocacy reach limitations.
It requires further validation from patients who experienced relapse to identify omitted factors.
Genetic predictability is evolving, and individualized risk assessment is not yet fully precise.

5. Availability and Access

The decision aid is detailed in articles on the aHUS Alliance Action website:
“AN aHUS PATIENT’S TREATMENT DISCONTINUATION MODEL” (July 16, 2024): Outlines the model and its use.
“Discontinuing complement inhibitor treatment” (October 22, 2024): Discusses feedback and utility.
Patients can access these resources online at www.ahusallianceaction.org and are encouraged to share the model with clinicians to guide discussions.

6. Broader Context and Other Conditions

aHUS-Specific Focus: The model is tailored to aHUS, where complement inhibitors like eculizumab are standard. Other complement-mediated diseases (e.g., paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulopathy) may have different discontinuation considerations, and no equivalent patient decision aid was identified for these conditions in the provided results.
General Decision Aids: While not specific to complement inhibitors, decision aids for treatment discontinuation in other fields (e.g., tyrosine kinase inhibitors for chronic myeloid leukemia) emphasize similar principles: weighing benefits (e.g., reduced side effects, costs) against risks (e.g., relapse), with adequate monitoring.

7. Challenges and Considerations

Relapse Risk: Studies highlight a 20-40% relapse rate, particularly in patients with genetic variants, necessitating close monitoring. Nonadherence increases relapse risk (odds ratio 8.25).
Infection Risks: Long-term complement inhibition raises the risk of meningococcal infections, even with vaccination, supporting discontinuation in low-risk patients.
Monitoring Feasibility: The model’s intensive monitoring (weekly tests, rapid reinitiation) may be challenging for patients in remote areas or with limited healthcare access.
Clinician Involvement: The decision must be joint, as clinicians assess genetic and clinical factors (e.g., renal function, pregnancy risk) not fully covered by the patient model.

Conclusion

The aHUS Alliance Global Action’s patient decision aid, published in July 2024, is a structured model to help aHUS patients decide on discontinuing complement inhibitor treatment (e.g., eculizumab, ravulizumab). It includes a relapse risk matrix, monitoring protocols, and a framework for clinician dialogue, based on global research showing 70-80% of patients remain in remission post-discontinuation with proper oversight. Available on www.ahusallianceaction.org, it has supported patients but requires further validation and is specific to aHUS. No equivalent decision aids were found for other complement-mediated diseases in the provided data. Patients should use this tool alongside clinician guidance, considering genetic risks and monitoring feasibility.

AI will be the future as far as interplay by patients with aHUS information available on line is concerned, but it will require patient generated content as provided by aHUS alliance Global Action for it to quote and cite. AI tools are already bringing viewers to this website because our research and development work is being cited.

Article No. 731