Table 4.
Patients and methods | Concomitant therapy | Endpoints | Results |
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A total of 381 patients with class III or class IV (80%) LN were randomised equally to receive either: placebo, OCR 400 mg or OCR 1,000 mg on days 1, 15 and every 16 weeks thereafter, >74% received three infusions and >50% received four infusions | In addition, either: MMF up to 3 g/day (63%); or EL (cyclophosphamide 500 mg ×6/2 weeks) followed by azathioprine 2 mg/kg up to 200 mg/day; and a steroid taper regimen - intravenous steroids: allowed up to 3 g by day 15, given in divided pulses), oral steroids: 0.5 to 0.75 mg/kg (≤60 mg/day) with taper to ≤10 mg over 10 weeks | Complete renal response: normal serum creatinine and ≤25% higher than baseline; urinary protein to creatinine ratio <0.5; inactive urinary sediment | In all modified intention-to-treat populations, there was a treatment difference of 12.2% with 54.7% vs. 66.9% for placebo (n = 75) and OCR (n = 148) groups, respectively |
Partial renal response: serum creatinine ≤25% above baseline value; and 50% improvement in the urine protein to creatinine ratio, and if baseline ratio >3.0 then a urine protein to creatinine ratio <3.0 | ORR higher in OCR (400 mg) + EL (65.6%) and OCR (1,000 mg) + EL (74.2%) groups vs. placebo + EL (42.9%), ORR was similar in OCR+ MMF (67.9%) vs. placebo + MMF (61.7%) | ||
Nonresponse: not achieving either a complete or partial renal response. Patients who died or discontinued the study prior to week 48 (and had no renal data within 12 weeks of week 48) were considered nonresponders | ≥50% reduction in urine protein-to-creatinine ratio occurred in 69.6% vs. 58.7 % for OCR and placebo groups, respectively | ||
Urine protein-to-creatinine ratio <0.5 was achieved in 39.9% vs. 37.3%
for OCR and placebo, respectively |
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Serious adverse effects imbalance appeared to be driven by the combination with MMF: OCR 400 mg (41.8%) compared with 1,000 mg OCR + MMF (24.1%) and placebo + MMF (21.3%). Serious adverse event rates in EL groups were not reported as higher in the OCR arms |
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Serious infection imbalance appeared to be driven by the OCR combination with MMF. MMF groups: OCR 400 mg (32.9%) compared with 1,000 mg OCR (19%) and placebo + MMF (16.3%). EL groups: OCR 400 mg (12.8%) compared with 1,000 mg OCR (10.4%) and placebo + MMF (11.1%) |
EL, EUROLUPUS regimen (cyclophosphamide followed by azathioprine); LN, lupus nephritis; MMF, mycophenolate mofetil; OCR, ocrelizumab; ORR, overall renal response.