A Study of Mycophenolate Mofetil (CellCept) in Management of Patients With Lupus Nephritis.

Treatment response was adjudicated by a blinded clinical endpoints committee (CEC) and defined as: a) Decrease in proteinuria, defined as a decrease in the urine protein to creatinine ratio (UPCr) to \<3 in subjects with baseline proteinuria ≥3 UPCr or a decrease in the UPCr by ≥50% in subjects with proteinuria \<3 UPCr at Baseline, and b) Stabilization of serum creatinine or improvement. UPCr were derived from the 24 hour urine collection. Patients who did not show a treatment response at Week 24 or who withdrew earlier than Week 24 were considered non-responders.

Time frame: 24 weeks

Population: Analysis population was intent to treat which comprised all subjects who were randomized into the study and had at least one post-baseline efficacy assessment.

Treatment Failure was adjudicated by a clinical endpoints committee and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to treatment failure for each patient. The data presented are the percentage of participants who were treatment-failure free at each time interval as estimated by Kaplan-Meier.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Intent to treat analysis population which consisted of all subjects who were randomized to the maintenance phase of the study and had at least 1 maintenance efficacy assessment.

The SF-36 is a 36 item quality of life questionnaire. The short-form version has eleven questions that permit the participant to rate how they feel that particular day. The SF-36 consists of eight scaled scores and two component scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 score with the higher scores indicating better quality of life.

Time frame: Baseline and 24 weeks

Population: This analysis population is intention to treat. The analysis included only those patients for whom data was available at both time points, as indicated by n.

24-hour urine protein was measured at Baseline and Week 24.

Time frame: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by n.

Time frame: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by n.

Time frame: Baseline, Week 24

Population: Analysis population was intent to treat. The analysis included only those patients for whom data was available at both time points, as indicated by n.

BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system. The BILAG individual system summaries were calculated by a program supplied by ADS-Limathon (Sheffield, UK). The score at baseline was compared to the score at the 24 week endpoint for each treatment group, reported here for the renal system.

Time frame: Baseline, 24 weeks

Population: Analysis population was intent to treat. The endpoint was defined using the last observation carried forward approach. If no post-Baseline value was available, endpoint was considered missing.

Number of participants achieving complete remission as defined by return to normal serum creatinine, proteinuria ≤500 mg/24 hours and an inactive urinary sediment (absence of red blood cells, white blood cells or cellular or granular casts) after 24 weeks.

Time frame: 24 weeks

Population: Analysis population was intent to treat.

The primary efficacy parameter was the time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), defined as any of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. Kaplan-Meier survival curves were estimated from the observed time to rescue treatment for each patient. The data presented are the percentage of participants who were rescue treatment free at each time interval as estimated by Kaplan-Meier.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.

A proteinuric flare is defined as a doubling of the urine protein:creatinine ratio, and proteinuria ≥1 g/24 h in patients with urine protein ≤0.5 g/24 h at the end of the induction phase, or proteinuria ≥2 g/24 h if urine protein was \>0.5 g/24 h at the end of the induction phase. A nephritic flare is defined as a 25% increase in serum creatinine accompanied by 1 or more of the following: (a) simultaneous doubling of the proteinuria reaching a minimum of 2 g/24 h (b) new/increased hematuria or (c) the appearance of cellular casts. All flares were adjudicated by a clinical endpoints committee.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.

Treatment Failure was adjudicated by a clinical endpoints committee (CEC) and was defined as the time to the earliest occurrence of any one of the following: death, end stage renal disease, sustained doubling of serum creatinine, renal flare, or a requirement for rescue therapy for exacerbation or deterioration of Lupus nephritis (LN).

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population.

Time to treatment failure, adjudicated by the Clinical Endpoints Committee (CEC), was defined as any 1 the following: death, ESRD, sustained doubling of serum creatinine, renal flare (proteinuric or nephritic), or requirement for rescue therapy to treat deterioration or exacerbation of Lupus nephritis. ESRD is defined as progression to chronic hemodialysis or renal transplant.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.

Sustained doubling of serum creatinine concentration is defined as the first serum creatinine value that is twice the mean of the lowest 2 values from screening to end of induction, as confirmed by a second serum creatinine value obtained at least 4 weeks after the initial doubling.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population. The analysis includes all event data, regardless of whether or not the event was the earliest Clinical Endpoints Committee-adjudicated reason for treatment failure.

A major extra-renal flare is defined as a British Isles Lupus Assessment Group (BILAG) Score category A in one extrarenal organ or three organs with concurrent category B scores. BILAG indices provide a scoring system for the assessment of lupus disease activity in terms of the need for steroid treatment in 8 organs/systems. Eighty-six items were scored resulting in a classification of A (severe activity), B (moderate activity), C (mild activity), D (no current activity) and E (no activity ever observed) for each organ system.

Time frame: From the start of the Maintenance Phase to Month 36

Population: Maintenance Phase intent to treat population.