ade 3 or 4 diarrhea in two (1.1%) patients. No patients in Study 1 received systemic corticosteroids or immunosuppressants for diarrhea or colitis. In the combined safety database, immune-mediated colitis or diarrhea occurred in 18 (1.3%) patients including Grade 4 in one (<0.1%) and Grade 3 in four (0.3%) patients. The median time to onset was 73 days (range: 13-345 days). Of these patients, one (<0.1%) had Grade 4 and four (0.3%) had Grade 3 immune-mediated colitis or diarrhea. Ten (0.7%) of the 18 patients received high-dose corticosteroid treatment. Two (0.1%) patients received non-steroidal immunosuppressants. IMFINZI was interrupted in five (0.4%) patients and discontinued in six (0.4%) patients. Resolution occurred in 11 (0.8%) patients.
5.4 Immune-Mediated Endocrinopathies
Immune-related thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus and hypophysitis/hypopituitarism have occurred in patients receiving IMFINZI. Monitor patients for clinical signs and symptoms of endocrinopathies.
Thyroid Disorders
Monitor thyroid function prior to and periodically during treatment with IMFINZI. Asymptomatic patients with abnormal thyroid function tests can receive IMFINZI. Manage patients with abnormal thyroid function tests with hormone replacement (if indicated) and treatment modifications [see DOSAGE AND ADMINISTRATION (2.2)].
In the Study 1, hypothyroidism or thyroiditis leading to hypothyroidism occurred in ten (5.5%) patients. All patients had Grade 1-2 hypothyroidism. The median time to first onset was 42 days (range: 15-239). Thyroid stimulating hormone (TSH) was elevated and above the patient’s baseline in 25 (15.3%) of 163 patients with a follow-up measurement.
In Study 1, hyperthyroidism or thyroiditis leading to hyperthyroidism occurred in nine (4.9%) patients. All patients had Grade 1-2 hyperthyroidism. The median time to first onset was 43 days (range: 14-71). Thyroid stimulating hormone (TSH) was decreased and below the patient’s baseline in 26 (16%) of 163 patients with a follow-up measurement.
In the combined safety database, hypothyroidism occurred in 136 (9.6%) patients, while hyperthyroidism occurred in 81 (5.7%) patients. Thyroiditis occurred in ten patients, including Grade 3 in one patient who had a myocardial infarction. In nine patients with thyroiditis, transient hyperthyroidism preceded hypothyroidism. Treatment with a beta-blocker and/or thioamide was administered for hyperthyroidism in five of these patients.
Adrenal Insufficiency
Monitor patients for clinical signs and symptoms of adrenal insufficiency. Administer corticosteroids and hormone replacement as clinically indicated [see DOSAGE AND ADMINISTRATION (2.2)].
In Study 1, adrenal insufficiency occurred in one (0.5%) patient (Grade 1). In the combined safety database, adrenal insufficiency occurred in 13 (0.9%) patients, including Grade 3 in two (0.1%) patients. Seven (0.5%) of these patients were treated with systemic corticosteroids.
Type 1 Diabetes Mellitus
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate insulin for type 1 diabetes mellitus and manage patients with treatment modifications [see DOSAGE AND ADMINISTRATION (2.2)]. New onset type 1 diabetes mellitus without an alternative etiology occurred in one patient (<0.1%) in the combined safety database.
Hypophysitis
Monitor for signs and symptoms of hypophysitis or h |
