NULOJIX^® (belatacept) regimen demonstrated superior cGFR^* at Month 12,^† sustained through Month 36^‡ vs CsA regimen

Mean calculated glomerular filtration rate (cGFR)¹

^*cGFR was calculated using the MDRD formula.¹

^†Predefined secondary endpoint.²

^‡Predefined tertiary endpoint.²

CI=confidence interval.

SELECTED IMPORTANT SAFETY INFORMATION

Post-Transplant Lymphoproliferative Disorder (PTLD)

• NULOJIX patients are at increased risk for developing PTLD, predominantly involving the central nervous system (CNS)
• Recipients without immunity to EBV (ie, seronegative) are at particularly increased risk; therefore, NULOJIX is contraindicated in transplant recipients who are EBV seronegative or with unknown serostatus
• Monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms
• As the total burden of immunosuppression is a risk factor for PTLD, higher than recommended doses or more frequent dosing of NULOJIX or concomitant immunosuppressive agents are not recommended
• Other known risk factors for PTLD include cytomegalovirus (CMV) infection and T cell-depleting therapy
  • CMV prophylaxis is recommended for at least 3 months after transplantation
  • Use T cell-depleting therapy to treat acute rejection cautiously
• Patients who are EBV seropositive and CMV seronegative may be at increased risk of PTLD
  • Since CMV seronegative patients are at increased risk for CMV disease (a known risk factor for PTLD), the clinical significance of CMV serology for PTLD remains to be determined; however, these findings should be considered when prescribing NULOJIX

Distribution of patients by cGFR at Month 12 and Month 36^2-4

^*CKD=chronic kidney disease.

SELECTED IMPORTANT SAFETY INFORMATION

Management of Immunosuppression

• Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX
  • Patients should be managed in facilities with adequate laboratory and supportive medical resources
  • The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient

Renal function for patients receiving a kidney from living or standard criteria donors^1,5,6

SELECTED IMPORTANT SAFETY INFORMATION

Other Malignancies and Serious Infections:

• Increased susceptibility to infection and possible development of malignancies may result from immunosuppression
• Patients should avoid prolonged exposure to ultraviolet light and sunlight
• Patients receiving immunosuppressants, including NULOJIX, are at increased risk for bacterial, viral, fungal, and protozoal infections, including opportunistic infections and tuberculosis. Some infections were fatal
  • Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss; consider reduction in immunosuppression, weighing risk to the graft
  • Tuberculosis was more frequently observed in patients receiving NULOJIX. Evaluate for tuberculosis and initiate treatment for latent infection prior to NULOJIX use
  • CMV and Pneumocystis jiroveci prophylaxis is recommended after transplantation

Liver Transplant:

• Use in liver transplant patients is not recommended due to increased risk of graft loss and death in a clinical trial with more frequent administration of NULOJIX than studied in kidney transplant, along with MMF and corticosteroids

Evaluating outcomes in patients with BPAR

Kidney function at Month 12 and Month 36^1,3

The difference in mean cGFR between patients with and without history of BPAR was:

• At Month 12, 19 mL/min/1.73 m² among NULOJIX^® regimen-treated patients compared to 7 mL/min/1.73 m² among cyclosporine regimen-treated patients¹
• At Month 36, 25 mL/min/1.73 m² among NULOJIX regimen-treated patients compared to 6 mL/min/1.73 m² among cyclosporine regimen-treated patients³

SELECTED IMPORTANT SAFETY INFORMATION

Acute Rejection and Graft Loss with Corticosteroid Minimization

• In NULOJIX postmarketing experience, corticosteroid minimization to 5 mg/day between Day 3 and Week 6 post-transplant was associated with an increased rate and grade of acute rejection, particularly Grade III
  • These Grade III rejections occurred in patients with 4-6 human leukocyte antigen (HLA) mismatches
  • Graft loss was a consequence of Grade III rejection in some patients
• Corticosteroid utilization should be consistent with the NULOJIX clinical trial experience
  • Median (25th-75th percentile) corticosteroid doses were tapered to about 15 mg (10-20 mg)/day by the first 6 weeks and remained at about 10 mg (5-10 mg)/day for the first 6 months post-transplant

Graft loss and/or death at Month 12 and Month 36^1,3

The relationship between BPAR, GFR, and patient and graft survival is unclear due to the limited number of patients who experienced BPAR, differences in renal hemodynamics (and, consequently, GFR) across maintenance immunosuppression regimens, and the high rate of switching treatment regimens after BPAR.¹

SELECTED IMPORTANT SAFETY INFORMATION

Immunizations:

• Avoid use of live vaccines during NULOJIX treatment

Coadministration with Anti-Thymocyte Globulin:

• In de novo kidney transplant recipients, especially those with other predisposing risk factors for venous thrombosis of the renal allograft, coadministration (at the same or nearly the same time) with anti-thymocyte globulin may pose a risk for venous thrombosis of the renal allograft. If anti-thymocyte globulin (or any other cell-depleting induction treatment) and NULOJIX will be administered concomitantly, a 12-hour interval between the two administrations is suggested

Risk of Rejection with Conversion From a Calcineurin Inhibitor (CNI) Based Maintenance Regimen:

• Conversion of patients from a CNI based maintenance regimen increases the risk of acute rejection. Conversion of stable kidney transplant recipients from a CNI based maintenance regimen to a NULOJIX based maintenance regimen is not recommended unless the patient is CNI intolerant

Pregnancy:

• The data with NULOJIX use in pregnant women are insufficient to inform on drug-associated risk. NULOJIX is known to cross the placenta of animals. To monitor maternal-fetal outcomes of pregnant women who have received NULOJIX, or whose partners have received NULOJIX, healthcare providers are strongly encouraged to register pregnant patients in the Transplant Pregnancy Registry International (TPR) by calling 1-877-955-6877

Lactation:

• There are no data on the presence of NULOJIX in human milk or the effects on breastfed infants or human milk production to inform risk of NULOJIX to an infant during lactation. NULOJIX is excreted in rat milk and it is possible that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for NULOJIX, and any potential adverse effects on the breastfed child from NULOJIX or from the underlying maternal conditions

References

1. NULOJIX [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company.
2. Data on file. NULO 077. Bristol-Myers Squibb Company. Princeton, NJ.
3. Data on file. NULO 027. Bristol-Myers Squibb Company. Princeton, NJ.
4. Data on file. NULO 028. Bristol-Myers Squibb Company. Princeton, NJ.
5. Data on file. NULO 076. Bristol-Myers Squibb Company. Princeton, NJ.
6. Florman S, Becker T, Bresnahan B, et al. Three-year outcomes by donor type in phase III studies of belatacept vs cyclosporine in kidney transplantation (BENEFIT & BENEFIT-EXT). Presented at: 12th American Transplant Congress; June 2-6, 2012; Boston, MA.

NULOJIX^® (belatacept) regimen demonstrated superior cGFR^* at Month 12,^† sustained through Month 36^‡ vs CsA regimen

Mean calculated glomerular filtration rate (cGFR)¹

^*cGFR was calculated using the MDRD formula.¹

^†Predefined secondary endpoint.²

^‡Predefined tertiary endpoint.²

CI=confidence interval.

SELECTED IMPORTANT SAFETY INFORMATION

Most Common Adverse Reactions (≥20%) through 3 years:

• Anemia (45%), diarrhea (39%), urinary tract infection (37%), peripheral edema (34%), constipation (33%), hypertension (32%), pyrexia (28%), graft dysfunction (25%), cough (24%), nausea (24%), vomiting (22%), headache (21%), hypokalemia (21%), hyperkalemia (20%), and leukopenia (20%). No new adverse reactions were observed in the long-term extension (years 4-7) studies

Distribution of patients by cGFR at Month 12 and Month 36³

^*CKD=chronic kidney disease.

SELECTED IMPORTANT SAFETY INFORMATION

Post-Transplant Lymphoproliferative Disorder (PTLD)

• NULOJIX patients are at increased risk for developing PTLD, predominantly involving the central nervous system (CNS)
• Recipients without immunity to EBV (ie, seronegative) are at particularly increased risk; therefore, NULOJIX is contraindicated in transplant recipients who are EBV seronegative or with unknown serostatus
• Monitor for new or worsening neurological, cognitive, or behavioral signs and symptoms
• As the total burden of immunosuppression is a risk factor for PTLD, higher than recommended doses or more frequent dosing of NULOJIX or concomitant immunosuppressive agents are not recommended
• Other known risk factors for PTLD include cytomegalovirus (CMV) infection and T cell–depleting therapy
  • CMV prophylaxis is recommended for at least 3 months after transplantation
  • Use T cell-depleting therapy to treat acute rejection cautiously
• Patients who are EBV seropositive and CMV seronegative may be at increased risk of PTLD
  • Since CMV seronegative patients are at increased risk for CMV disease (a known risk factor for PTLD), the clinical significance of CMV serology for PTLD remains to be determined; however, these findings should be considered when prescribing NULOJIX

Evaluating outcomes in patients with BPAR

Kidney function at Month 12 and Month 36^1,3

The difference in mean cGFR between patients with and without history of BPAR was:

• At Month 12, 10 mL/min/1.73 m² among NULOJIX  regimen-treated patients compared to 14 mL/min/1.73 m² among cyclosporine regimen-treated patients¹
• At Month 36, 15 mL/min/1.73 m² among NULOJIX regimen-treated patients compared to 12 mL/min/1.73 m² among cyclosporine regimen-treated patients³

Graft loss and/or death at Month 12 and Month 36^1,3

The relationship between BPAR, GFR, and patient and graft survival is unclear due to the limited number of patients who experienced BPAR, differences in renal hemodynamics (and, consequently, GFR) across maintenance immunosuppression regimens, and the high rate of switching treatment regimens after BPAR.¹

SELECTED IMPORTANT SAFETY INFORMATION

Management of Immunosuppression

• Only physicians experienced in immunosuppressive therapy and management of kidney transplant patients should prescribe NULOJIX
  • Patients should be managed in facilities with adequate laboratory and supportive medical resources
  • The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient

References

1. NULOJIX [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company.
2. Data on file. NULO 077. Bristol-Myers Squibb Company. Princeton, NJ.
3. Data on file. NULO 022. Bristol-Myers Squibb Company. Princeton, NJ.