Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial
Bibliographic record
Abstract
Significance Statement In patients with steroid-dependent and calcineurin inhibitor–depe ndent nephrotic syndrome, rituximab, a chimeric monoclonal anti body directed against CD20+ B cells, helps maintain remission, but relapse within a year is common. This randomized trial investigated wheth er ofatumumab, a fully human anti-CD20 monoclonal antibody, is superior to rituximab in maintaining oral drug–free remission in patients with this condition. The findings show ofatumumab is not superior to rituximab in achieving oral drug–free remission at 1 year of follow-up, and had similar adverse effects. Although ofatumumab treatment resulted in a more prolonged depletion of B cells compared with rituximab, this did not translate into clinical effects. These findings suggest human or humanized anti-CD20 antibodies may not offer advantages over the chimeric anti-CD20 rituximab for treatment of idiopathic nephrotic syndrome. Background The chimeric anti-CD20 monoclonal antibody rituximab is effective in steroid-dependent and calcineurin inhibitor–dependent forms of nephrotic syndrome, but many patients relapse at 1 year. Because ofatumumab, a fully human anti-CD20 monoclonal antibody, has a more extended binding site and higher affinity to CD20 compared with rituximab, it might offer superior efficacy in these patients. Methods We designed a single-center randomized clinical trial to compare the long-term efficacy of ofatumumab versus rituximab in children and young adults with nephrotic syndrome maintained in remission with prednisone and calcineurin inhibitors. We randomized 140 children and young adults (aged 2–24 years) to receive intravenous ofatumumab (1.50 mg/1.73 m 2 ) or rituximab (375 mg/m 2 ). After infusions, oral drugs were tapered and withdrawn within 60 days. The primary outcome was relapse at 1 year, which was analyzed following the intent-to-treat principle. The secondary endpoint was relapse within 24 months from infusion, on the basis of urine dipstick and confirmed by a urine protein-to-creatinine ratio <200. Results At 12 months, 37 of 70 (53%) participants who received ofatumumab experienced relapse versus 36 of 70 (51%) who received rituximab (odds ratio [OR], 1.06; 95% confidence interval [95% CI], 0.55 to 2.06). At 24 months, 53 of 70 (76%) participants who received ofatumumab experienced relapse, versus 46 of 70 (66%) who received rituximab (OR, 1.6; 95% CI, 0.8 to 3.3). The two groups exhibited comparable B cell subpopulation reconstitution and did not differ in adverse events. Conclusions A single dose of ofatumumab was not superior to a single dose of rituximab in maintaining remission in children with steroid-dependent and calcineurin inhibitor–dependent nephrotic syndrome. Clinical Trial registration numbers: ClinicalTrials.gov (NCT02394119) and https://www.clinicaltrialsregister.eu/ctr-search/search (2015–000624–28).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.004 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".