A Study to Assess the Safety and Efficacy of Alefacept in Kidney Transplant Recipients

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.

The Kaplan-Meier estimates at Day 182 was used for the analyses at 6 months. Lost to follow-up or patients with missing outcomes were censored at their last follow up visit.

Patient survival is any participant who is known to be alive 6 months and 12 months after the skin closure date.

The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months and 12 months after the skin closure date. Graft loss was defined as patient death, retransplant, permanent return to dialysis (dialysis greater than 30 days) or transplant nephrectomy.

The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.

The Kaplan-Meier estimates at Day 365 was used for the analyses at 12 months. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

Rejection episodes were confirmed by biopsy by a central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR.

The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.

The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

Rejection episodes were confirmed by biopsy by the central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR.

The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) method.

The glomerular filtration rate was measured directly using iothalamate clearance.

Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to local review, or lost to follow-up.

Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to central review, or lost to follow-up.

The time to first BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.

The time to first BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a BCAR are included in the analysis.

The time to first T-cell mediated BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1.

The time to first T-cell mediated BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1. Only participants with a T-cell mediated BCAR are included in the analysis.

The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.

Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.

The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis.

Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.

Patients who received immunosuppressive medications for the treatment of suspected or BCAR were considered to have a clinically-treated acute rejection.

Participants with histologically proved Banff Grade II or III rejection could receive anti-rejection therapy with anti-lymphocyte antibodies per institutional protocol.

The use of anti-lymphocyte antibody therapy at any time during a suspected or proven rejection episode for the treatment of acute rejection was considered an event.

All participants were evaluated for the incidence of multiple rejection episodes (clinically treated and/or BCAR as assessed by the local reviewer) through 6 months and 12 months.

Treatment failure was defined as death, graft loss, BCAR (local review), lost to follow-up or early discontinuation of treatment regimen. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.

The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI) symptom severity score. The GIQLI is a 36-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past 2 weeks on a scale from 0 (all of the time) to 4 (never). Possible overall scores ranged from 0 to 4, with higher scores indicating a better quality of life according to the different symptomatic criteria.

The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Symptom Rating Scale Scores (GSRS). The GSRS a 15-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to gastrointestinal symptoms.