The Current Uncertainty in C3G Medication Treatment Discontinuation

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Expert Panel Discussion on Duration of Complement Inhibitor Therapy in C3G

During a recent expert panel discussion, leading nephrologists shared their perspectives on the duration of treatment with newly approved complement inhibitors for C3G, highlighting the current uncertainties and clinical considerations in the absence of long-term data.

Key Takeaways:

Uncertainty on Treatment Duration:

• There is currently no established guidance or data regarding how long patients should remain on complement inhibitors.
• Bradley Dixon, MD, emphasized parallels with atypical hemolytic uremic syndrome, where initial assumptions of lifelong therapy have evolved to a more individualized approach based on genetic and clinical risk factors.

Current Approach—Lifelong or Long-Term Therapy:

• In the absence of markers to predict safe discontinuation, physicians are leaning toward prolonged, potentially lifelong therapy.
• Bradley Dixon, MD and Andrew S. Bomback, MD, MPH, both agreed that, at present, complement inhibitors would likely be continued long-term until more post-marketing data becomes available.

Criteria for Considering a Drug Holiday:

• Andrew S. Bomback, MD, MPH, suggested that any consideration of tapering or a drug holiday would require:
  • At least 2 to 5 years of stable therapy
  • Evidence of disease stability (e.g., no hematuria, minimal proteinuria, stable eGFR) over a sustained period (e.g., 1 year)
  • Willingness to closely monitor and reinstitute therapy at the first sign of disease recurrence

Challenges With Therapy Discontinuation:

• Patients with recurrent disease in kidney allografts are unlikely candidates for therapy discontinuation.
• There are anecdotal cases from prior generations (e.g., patients with membranoproliferative glomerulonephritis treated with prolonged steroids) where sustained remission without ongoing immunosuppression was achieved, providing cautious optimism.

Need for Collaborative Data Sharing:

• Jonathan Barratt, MBChB, PhD, FRCP, stressed the importance of the academic nephrology community in systematically collecting, reporting, and sharing outcomes related to treatment duration and discontinuation in C3G.
• Real-world evidence, genetic profiling, and detailed patient follow-up will be essential to develop future guidelines.

Clinical Implication:

Until further evidence is available, physicians should approach discontinuation of complement inhibitors in C3G with caution. Treatment is expected to be long term, with close monitoring and individualized decision-making being key. Collaboration and data sharing across centers will be critical to inform safe and effective treatment strategies in the future.