Permanently discontinue YERVOY for clinically significant or severe immune-mediated adverse reactions. Initiate systemic corticosteroids at a dose of 1 to 2 mg/kg/day prednisone or equivalent for severe immune-mediated adverse reactions.

Administer corticosteroid eye drops to patients who develop uveitis, iritis, or episcleritis. Permanently discontinue YERVOY for immune-mediated ocular disease that is unresponsive to local immunosuppressive therapy. [See Dosage and Administration (2.2)]

6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling.

Immune-mediated enterocolitis [see Warnings and Precautions (5.1)].
Immune-mediated hepatitis [see Warnings and Precautions (5.2)].
Immune-mediated dermatitis [see Warnings and Precautions (5.3)].
Immune-mediated neuropathies [see Warnings and Precautions (5.4)].
Immune-mediated endocrinopathies [see Warnings and Precautions (5.5)].
Other immune-mediated adverse reactions, including ocular manifestations [see Warnings and Precautions (5.6)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared with rates in other clinical trials or experience with therapeutics in the same class and may not reflect the rates observed in clinical practice.

The clinical development program excluded patients with active autoimmune disease or those receiving systemic immunosuppression for organ transplantation. Exposure to YERVOY 3 mg/kg for four doses given by intravenous infusion in previously treated patients with unresectable or metastatic melanoma was assessed in a randomized, double-blind clinical study (Study 1). [See Clinical Studies (14)] One hundred thirty-one patients (median age 57 years, 60% male) received YERVOY as a single agent, 380 patients (median age 56 years, 61% male) received YERVOY with an investigational gp100 peptide vaccine (gp100), and 132 patients (median age 57 years, 54% male) received gp100 peptide vaccine alone. Patients in the study received a median of 4 doses (range 1 to 4 doses). YERVOY was discontinued for adverse reactions in 10% of patients.

The most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue, diarrhea, pruritus, rash, and colitis.

Table 1 presents selected adverse reactions from Study 1, which occurred in at least 5% of patients in the YERVOY-containing arms and with at least 5% increased incidence over the control gp100 arm for all-grade events and at least 1% incidence over the control group for Grade 3–5 events.

Table 1: Selected Adverse Reactions in Study 1 a Incidences presented in this table are based on reports of adverse events regardless of causality.
 Percentage (%) of Patientsa
 YERVOY
3 mg/kg
n=131 YERVOY
3 mg/kg+gp100
n=380 gp100
n=132
System Organ Class/
Preferred Term Any
Grade Grade
3–5 Any
Grade Grade
3–5 Any
Grade Grade
3–5
Gastrointestinal Disorders      
Diarrhea 32 5 37 4 20 1
Colitis 8 5 5 3 2 0
Skin and Subcutaneous Tissue Disorders      
Pruritus 31 0 21 <1 11 0
Rash 29 2 25 2 8 0
General Disorders and Administration Site Conditions