- Design
- real-world observational cohort of patients treated outside clinical trials, identified through the CompCure registry and an international survey
- Population
- 25 paediatric and adult patients (18 C3 glomerulonephritis, 3 dense deposit disease, 4 primary IC-MPGN), median age 14.9 years, largely resistant to conventional immunosuppression
- Primary outcome
- change in urine protein-to-creatinine ratio, eGFR and serum C3 at 1, 3, 6 and 12 months
- Effect
- uPCR down 81% at 6 months from a median 3.5 g/g, 68% below 1 g/g, 12% complete and 64% partial remission; eGFR +9.4 mL/min/1.73 m2 at month 3 and +12 at month 6
C3 glomerulopathy and primary immune-complex membranoproliferative glomerulonephritis are driven by complement dysregulation, and conventional immunosuppression fails in a large share of patients, most of whom are young. Pegcetacoplan inhibits C3 and C3b. This cohort reports what happened when it was used outside clinical trials, in patients identified through the CompCure registry and an international survey.
Twenty-five patients started treatment: 18 with C3 glomerulonephritis, three with dense deposit disease and four with primary IC-MPGN. Median age at initiation was 14.9 years, a median 2.7 years after diagnosis. Baseline median urine protein-to-creatinine ratio was 3.5 g/g, mean eGFR 74 mL/min/1.73 m2, and 19 of 25 had low serum C3.
Proteinuria fell by a median 81% within six months, with 68% reaching below 1 g/g, 12% in complete and 64% in partial remission. Serum C3 normalised or rose above normal in every case but one, where non-adherence was suspected. Mean eGFR rose by 9.4 mL/min/1.73 m2 at month three and 12 at month six, and remained stable at twelve months where follow-up existed. No serious adverse events were recorded across 222 patient-months of exposure.
A rise in eGFR alongside an 81% fall in proteinuria in a disease that otherwise progresses is a substantial signal, and the biochemical coherence, C3 normalising as proteinuria fell, supports the mechanism. But this is 25 patients, uncontrolled, selected because they were treated, and sequential biopsies in the four patients who had them ranged from complete disappearance of C3 deposits to persistence alongside chronic damage. The right conclusion is that complement inhibition works in a disease that badly needs something, and that patient selection and treatment duration are still unresolved. Treat availability and cost as the immediate practical barriers; nothing here establishes access in India.
- Confirm the diagnosis on biopsy with complement staining before considering C3 inhibition; C3G and IC-MPGN are distinguished histologically
- Measure serum C3 at baseline and follow it: it normalised in almost every responder and flagged the one suspected non-adherence
- Track urine protein-to-creatinine ratio as the working response measure, aiming below 1 g/g
- Counsel on meningococcal risk and vaccination requirements before starting any complement inhibitor
- Read a 25-patient uncontrolled cohort as evidence the drug does something, not as evidence about who should get it
The statistics, in plain English
There is no control group, so the comparison is each patient against their own baseline, and diseases with fluctuating proteinuria can improve for reasons unrelated to treatment. What makes this more than anecdote is the consistency: proteinuria fell in most patients, eGFR rose rather than merely stabilising, and serum C3 moved in the direction the drug's mechanism predicts. With 25 patients, percentages carry few people each, so 12% complete remission means three patients. Safety across 222 patient-months cannot exclude uncommon harms, and complement inhibitors carry a known meningococcal risk that a cohort this size would not be expected to detect.
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