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Case Report/Case Series |

Severe Hypertriglyceridemia With Pancreatitis:  Thirteen Years’ Treatment With Lomitapide

Frank M. Sacks, MD1,2,3; Maxine Stanesa, PA-C4; Robert A. Hegele, MD5
[+] Author Affiliations
1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
2Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
3Harvard Medical School, Boston, Massachusetts
4Harvard Vanguard Medical Associates, Boston, Massachusetts
5Robarts Research Institute, London, Ontario, Canada
JAMA Intern Med. 2014;174(3):443-447. doi:10.1001/jamainternmed.2013.13309.
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Importance  Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments.

Observations  We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years.

Conclusions and Relevance  Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.

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Figure 1.
Serum Fasting Triglyceride Concentrations at Baseline (B) and During the First Year of Treatment With Lomitapide

The dose of lomitapide was adjusted to balance efficacy and tolerability. The patient’s triglyceride level when receiving 12.5 mg/d averaged 2110 mg/dL, when receiving the alternating dose regimen of 12.5 mg/d and 25 mg/d averaged 1416 mg/dL, and when receiving 25 mg/d averaged 371 mg/dL. Discontinued indicates temporary cessation of lomitapide. (To convert triglycerides to millimoles per liter, multiply by 0.0113.)

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Figure 2.
Serum Fasting Triglyceride (TG) Concentrations During Years 2 to 13 of Treatment With Lomitapide

Each episode of pancreatitis (P) is defined as brief uncomplicated hospitalization associated with not taking the drug or exceptionally high dietary fat intake (The 2 P’s close to each other are simply 2 pancreatitis episodes that occurred at the times indicated on the x-axis). At year 4, a 6-month trial of adding fenofibrate, 200 mg/d, to lomitapide, 12.5 mg/d, to try to control the hypertriglyceridemia on a lower dose of lomitapide was a failure. The patient’s mean serum TG level was 3175 mg/dL (range, 2525-3880 mg/dL; N = 4 TG tests) with the combination, compared with 2345 mg/dL (range, 1041-3600 mg/dL; N = 6 TG measurements) during treatment with lomitapide, 12.5 mg/d. This time period is indicated by vertical gray columns. In the 10th year, lomitapide was reformulated into 20- and 40-mg capsules. The mean (SD) TG levels during treatment with 20 mg/d was 1604 (1030) mg/dL (median, 1331 mg/dL; N = 13 TG measurements); during treatment with the alternating dose of 20 mg/d and 40 mg/d, 903 (870) mg/dL (median, 703 mg/dL; N = 10 TG measurements); and during treatment with the 40-mg/d dose, 524 (265) mg/dL (median, 542 mg/dL; N = 4 TG measurements). B indicates baseline. (To convert TG to millimoles per liter, multiply by 0.0113.)

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Figure 3.
Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Baseline and During 13 Years’ Treatment With Lomitapide

The upper limits of normal were 40 U/L for ALT (A) and 35 U/L for AST (B). Findings of the liver biopsy described in more detail in the subsection titled “Hepatic Toxicity of Lomitapide.” B indicates baseline. (To convert ALT and AST to microkatals per liter, multiply by 0.0167.)

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