Vitamin D3 in Systemic Lupus Erythematosus

Presence of an Interferon (IFN) Alpha signature response is defined as: a reduction in expression from baseline (Screening) of at least 50% for 1 of 3 IFN Alpha responsive genes (Ifit1, Ifi44, Mx1) with concurrent expression in the remaining 2 genes at a level not more than 25% above baseline, or a reduction in expression from baseline of at least 25% for 2 of the 3 IFN Alpha responsive genes with concurrent expression in the third gene at a level of no more than 25% above baseline. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were considered as response failures during calculation.

An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

An Interferon (IFN) Alpha signature is defined as: expression of Mx1, Ifit1, or Ifi44 at a level greater than or equal to 4 standard deviations above the mean of a set of normal controls, or expression of 2 of the 3 genes at a level greater than or equal to 2 standard deviations above the mean of a set of normal controls. Gene expression was measured on peripheral blood samples using qRT-PCR. Missing data were assumed as signatures during calculation.

The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. This gene encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

The Ifit1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes an interferon-induced protein with tetratricopeptide repeats. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

The Ifi44 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes interferon-induced protein 44. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 12 is represented as a negative value (and vice versa).

The Mx1 gene is one of three genes included in the definition of the alpha-interferon signature used for this study. It encodes for the homolog of mouse myxovirus (influenza virus) resistance 1 protein. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure gene expression in peripheral blood mononuclear cells obtained by blood draw. Gene expression is quantified as "fold change" relative to normal controls and is computed using a comparative CT (threshold cycle) method. A study hypothesis was that expression of alpha-interferon signature genes would decrease with increasing vitamin D levels. A decrease in gene expression from baseline to Week 6 is represented as a negative value (and vice versa).

C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 12 is represented as a positive value (and vice versa).

C3 is a blood test that measures the activity of the complement component 3 (C3) protein. The normal C3 range is 75 to 135 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C3. A decrease in C3 level over time may indicate disease activity. An increase in C3 from baseline to Week 6 is represented as a positive value (and vice versa).

C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 12 is represented as a positive value (and vice versa).

Outcome measure description: C4 is a blood test that measures the activity of the complement component 4 (C4) protein. The normal range for males is 12 to 72 mg/dL and the normal range for females is 13 to 75 mg/dL. Patients with active systemic lupus erythematosus may have a lower-than-normal level of C4. A decrease in C4 level over time may indicate disease activity. An increase in C4 from baseline to Week 6 is represented as a positive value (and vice versa).

Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

Patients with systemic lupus erythematosus (SLE) may have autoantibodies (e.g., self against self) to double-stranded DNA. Double-stranded DNA is one of multiple diagnostic tests for SLE and levels may be associated with disease activity. A positive test for autoantibodies to double-stranded DNA is based on the normal range from the local laboratory. Change in status (+ or -) from baseline is evaluated.

The modified Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus (SLE) Disease Activity Index (SELENA-SLEDAI) score is a weighted scale score ranging from 0 to 105 based on the presence or absence of 24 manifestations of SLE. The SELENA-SLEDAI assesses disease activity for 10 days prior to and including the day of assessment. For this study, the SELENA-SLEDAI score was modified to include proteinuria defined by dipstick rather than 24 hour urine. Positive change in the SELENA-SLEDAI score indicate increased disease activity.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Cardiorespiratory-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Constitutional-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Gastrointestinal-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Hematological-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Mucocutaneous-specific" body system.

Outcome measure description: The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Musculoskeletal-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Neuropsychiatric-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Ophthalmic-specific" body system.

The British Isles Lupus Assessment Group (BILAG) assessment gives a grade for each of 9 body systems (e.g., domains). Grades reflect systemic lupus erythematosus disease activity as follows: A (severe), B (moderate), C (mild), D (inactive at present but previously affected), E (inactive and system never involved). To be randomized, subjects had to have mild or inactive disease (C,D,E) in all but the mucocutaneous system in which B(moderate) disease was also allowed. The percent of subjects experiencing A or B level activity at Week 12 is assessed for the "Renal-specific" body system.

Grades are based on National Cancer Institute--Common Terminology Criteria (NCI-CTCAE) Version 3.0 over the duration of the study. Participants who experienced at least one grade 3 or higher adverse event (AE) are counted only once. The adverse events are treatment-emergent, which means that the AE occurred after taking the first dose of study drug.