Table 2.
Definition of disease attribute prevalence at baseline and post-metreleptin treatment and definition of improvement
| Attribute | Baseline definition | Outcome definition | Definition of improvement |
|---|---|---|---|
| Disruption to female reproductive function | Irregular menstruation or PCOSa | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | More regular menstruation or decreased signs/symptoms of PCOS by last NIH visit based on patient chart notes |
| Heart abnormality | Hypertrophy, any dilation, any regurgitation, cardiomyopathy, and tachycardia (excludes hypertension) | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | N/A—Clinical improvement could not be determined with available data |
| Hypertensionb | Stage 2 hypertension: Systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg | Complete control: Systolic <120 mm Hg and diastolic <100 mm Hg | Early improvement: 1-stage improvement in baseline hypertension categorization by year 1 |
|
Stage 1 hypertension: Systolic ≥ 140 mm Hg or <160 mm Hg; or diastolic <100 mm Hg or ≥90 mm Hg Prehypertensive: Systolic ≥120 mm Hg and <140 mm Hg; or diastolic ≥80 mm Hg and <90 mm Hg |
Partial control: ≥1-stage improvement from baseline No control/worsening: Same as baseline definition |
Late improvement: 1-stage improvement in baseline hypertension categorization after year 1 | |
| Hyperphagia | Clinician-documented excessive hunger | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | Clinician-documented reduction in excessive hunger |
| Hyperglycemia | No blood sugar control: HbA1c > 8% | Complete control: HbA1c <6.5% | Early improvement: ≥20% reduction in HbA1c % by year 1 |
| Partial blood sugar control: HbA1c > 6.5% to ≤8% | Partial control: HbA1c ≥ 6.5% to ≤8% after 1 year | ||
| No control/worsening: HbA1c > 8% after 1 year | Late improvement: ≥20% reduction in HbA1c % after year 1 | ||
| Complete blood sugar control: Hba1C <6.5% | Same as baseline definition | N/A | |
| Hypertriglyceridemia | No triglyceride control: >500 mg/dL |
Complete triglyceride control: <200 mg/dL Partial triglyceride control: >200 to ≤500 mg/dL No triglyceride control / worsening: >500 mg/dL after 1 year |
Early improvement: ≥20% reduction in triglyceride levels by year 1 Late improvement: ≥20% reduction in triglyceride levels after year 1 |
| Partial triglyceride control: >200 to <500 mg/dL | |||
| Complete triglycerides control: <200 mg/dL | Same as baseline definition | N/A | |
| Impaired physical appearance | Acanthosis nigricans, hyperkeratosis, or hirsutism | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | Diminished acanthosis nigricans, hyperkeratosis, or hirsutism based on patient chart notes |
| Kidney abnormality | Proteinuria, enlarged kidneys, nephropathy, hydronephrosis, renal disease, nephromegaly, renal failure, renal calculus, and glomerulosclerosis | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | ≥20% reduction in 24-hour protein excretion at year 1 if elevated (>150 mg/24 hrs) at baseline; if additional kidney condition emerged between metreleptin initiation and 1.5 years post-metreleptin (exclusive), then patient was not considered to improve; improvement was not measured for patients without elevated protein excretion at baseline |
| Liver abnormality | Any form of fatty liver or steatosis, fibrosis, cirrhosis, hepatitis, >2x normal levels of ALT (females, >50 U/L; males >66 U/L) and AST (>40 U/L), and hepatomegalyc | Same as baseline definition; continued or newly emergent symptoms after initiation of treatment | ≥20% reduction in ALT or AST at year 1 if elevated at baseline |
| If both ALT and AST were elevated at baseline, both ALT and AST must have 20% reduction at year 1 to be considered improved | |||
| If only one of the laboratory values was considered elevated at baseline, that value must show a ≥20% reduction and the other laboratory values must remain nonelevated at year 1 to be considered improved. Improvement was not measured for patients without elevated ALT or AST at baseline | |||
| Pancreatitis | ≥1 recorded episode of pancreatitis | ≥1 recorded episode of pancreatitis after treatment initiation that did not occur in the context of noncompliance with metreleptin treatment | No recorded episodes of pancreatitis after initiation of metreleptin among patients with a history of pancreatitisd |
| Progression of organ damage |
Fast progression: Organ progression rate ≤9 years/organe Slow progression: Organ progression rate >9 years/organe |
Fast progression: Development of first organ abnormality in the first 3 years of treatment Slow progression: Development of first organ abnormality after the first 3 years of treatment |
N/A—Improvement was not measured |
| Inability to work/attend school | Incomplete school attendance due to disease symptoms (school-age) or not working/working part-time due to disease symptoms (adults) | Same as baseline definition; continued or newly emergent after initiation of treatment | Full school attendance (school-age) or the ability for a patient to work, even if the patient has chosen not to work (adults) |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; HbA1c, glycated hemoglobin; NIH, National Institutes of Health; PCOS, polycystic ovary syndrome.
aExcluded subjects in menopause, prepubescent, or status after surgical removal of reproductive organs.
bPatients’ baseline and year 1 hypertension data needed to be available to be included in the count and percent for hypertensive (n = 105).
cHepatomegaly values were not consistently reported.
dExcludes pancreatitis that occurred in the context of noncompliance with metreleptin treatment.
eDefined as the patients’ age at the beginning of treatment divided by the patients’ initial number of organ impairments (kidney, heart, liver, or pancreatitis).