Metreleptin Disease Interactions

Cases of T-cell lymphoma have been reported during treatment with metreleptin in patients with acquired generalized lipodystrophy. Some, but not all, had immunodeficiency and significant hematologic abnormalities including severe bone marrow abnormalities before the initiation of metreleptin therapy. However, lymphomas and other lymphoproliferative disorders have also been reported in patients with acquired generalized lipodystrophy who did not receive metreleptin, thus a causal relationship with metreleptin has not been established. Acquired lipodystrophies are associated with autoimmune disorders, and the latter is associated with an increased risk of malignancies including lymphomas. Until more information is available, the potential benefits and risks of metreleptin treatment should be carefully considered in patients with acquired generalized lipodystrophy and/or those with significant hematologic abnormalities including leukopenia, neutropenia, bone marrow abnormalities, lymphoma, and/or lymphadenopathy.

The use of metreleptin is contraindicated in patients with general obesity not associated with congenital leptin deficiency. Metreleptin has not been shown to be effective in treating general obesity. Moreover, development of anti-metreleptin antibodies with neutralizing activity has been reported in obese patients treated with metreleptin, the clinical consequences of which have not been well characterized but could include inhibition of endogenous leptin action and loss of metreleptin efficacy. Worsening metabolic control and/or severe infection have been reported.

Leptin is involved in immune system homeostasis. Patients with acquired lipodystrophies and leptin deficiency may have autoimmune disorders including autoimmune hepatitis and membranoproliferative glomerulonephritis. Progression of autoimmune hepatitis and membranoproliferative glomerulonephritis with massive proteinuria and renal failure has occurred in some patients with acquired generalized lipodystrophy treated with metreleptin, a recombinant analog of human leptin. A causal relationship between metreleptin treatment and the development and/or progression of autoimmune disease has not been established. Until more information is available, the potential benefits and risks of metreleptin treatment should be carefully considered in patients with autoimmune diseases.

Metreleptin can cause hypoglycemia. Caution is advised in patients that suffer from hypoglycemia or in diabetic patients in treatment with oral hypoglycemic agents or insulin. A dosage adjustment might be needed.