BENLYSTA® Special Drug Use Investigation

Primary outcomes

1. Number of Participants With Adverse Drug Reactions (ADRs)

   Time frame: From the start of the study intervention (Day 1) up to maximum of 3 years

   ADR is defined as a response to a drug which is noxious and unintended, and which occurred at doses normally used in human for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function.

2. Number of Participants With Serious ADR of Events Defined as a Priority Study Matter

   Time frame: From the start of the study intervention (Day 1) up to maximum of 3 years

   ADR is defined as a response to a drug which is noxious and unintended, and which occurred at doses normally used in human for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function. Following serious ADRs were considered as priority study matter: 1. Serious hypersensitivity, 2. Serious infections (including tuberculosis, pneumonia, pneumocystis pneumonia, sepsis, and opportunistic infection), 3. Reactivation of hepatitis B virus, 4. Progressive multifocal leukoencephalopathy, 5. Interstitial pneumonitis, 6. Malignant tumor, 7. Depression and events related to suicide/self-injury.

3. Change From Baseline in Safety of Estrogens in Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA SLEDAI) Score at Week 24

   Time frame: Baseline (Day 0) and Week 24

   The SELENA-SLEDAI score is a cumulative and weighted index for assessing systemic lupus erythematosus (SLE) disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

4. Change From Baseline in SELENA SLEDAI Score at Week 52

   Time frame: Baseline (Day 0) and Week 52

   The SELENA-SLEDAI score is a cumulative and weighted index for assessing systemic lupus erythematosus (SLE) disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

5. Change From Baseline in Lupus Impact Tracker Score at Week 24

   Time frame: Baseline (Day 0) and Week 24

   Lupus impact tracker is 10-item patient reported outcome tool to measure impact of systemic lupus erythematosus or its treatment on participants' daily lives. Each answer for items is marked from 0 (none of the time) to 4 (all of the time) points. Lower the lupus impact score, less impact lupus is having on life of participant. Total score was derived by adding up scores of all 10 items. Total score ranges from 0 (less impact on daily life) to 40 (greater impact on daily life). Higher score indicates greater impact of lupus on quality of life.

6. Change From Baseline in Lupus Impact Tracker Score at Week 52

   Time frame: Baseline (Day 0) and Week 52

   Lupus impact tracker is 10-item patient reported outcome tool to measure impact of systemic lupus erythematosus or its treatment on participants' daily lives. Each answer for items is marked from 0 (none of the time) to 4 (all of the time) points. Lower the lupus impact score, less impact lupus is having on life of participant. Total score was derived by adding up scores of all 10 items. Total score ranges from 0 (less impact on daily life) to 40 (greater impact on daily life). Higher score indicates greater impact of lupus on quality of life.

7. Change From Baseline in Physician's Global Assessment (PGA) Score at Week 24

   Time frame: Baseline (Day 0) and Week 24

   The PGA is used to assess the participant's current disease activity by investigator. It was collected on a 10 centimeter (cm) visual analogue scale (VAS). The score ranges from 0 (no activity) to 3 (severe activity). Lower score means no disease activity, higher score means severe disease activity. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

8. Change From Baseline in PGA Score at Week 52

   Time frame: Baseline (Day 0) and Week 52

   The PGA is used to assess the participant's current disease activity by investigator. It was collected on a 10 centimeter (cm) visual analogue scale (VAS). The score ranges from 0 (no activity) to 3 (severe activity). Lower score means no disease activity, higher score means severe disease activity. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

9. Percent Change From Baseline in Mean Daily Steroid Dose at Week 4

   Time frame: Baseline (Day 0) and Week 4

   Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

10. Percent Change From Baseline in Mean Daily Steroid Dose at Week 8

    Time frame: Baseline (Day 0) and Week 8

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

11. Percent Change From Baseline in Mean Daily Steroid Dose at Week 12

    Time frame: Baseline (Day 0) and Week 12

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

12. Percent Change From Baseline in Mean Daily Steroid Dose at Week 16

    Time frame: Baseline (Day 0) and Week 16

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

13. Percent Change From Baseline in Mean Daily Steroid Dose at Week 20

    Time frame: Baseline (Day 0) and Week 20

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

14. Percent Change From Baseline in Mean Daily Steroid Dose at Week 24

    Time frame: Baseline (Day 0) and Week 24

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

15. Percent Change From Baseline in Mean Daily Steroid Dose at Week 28

    Time frame: Baseline (Day 0) and Week 28

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

16. Percent Change From Baseline in Mean Daily Steroid Dose at Week 32

    Time frame: Baseline (Day 0) and Week 32

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

17. Percent Change From Baseline in Mean Daily Steroid Dose at Week 36

    Time frame: Baseline (Day 0) and Week 36

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

18. Percent Change From Baseline in Mean Daily Steroid Dose at Week 40

    Time frame: Baseline (Day 0) and Week 40

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

19. Percent Change From Baseline in Mean Daily Steroid Dose at Week 44

    Time frame: Baseline (Day 0) and Week 44

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

20. Percent Change From Baseline in Mean Daily Steroid Dose at Week 48

    Time frame: Baseline (Day 0) and Week 48

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

21. Percent Change From Baseline in Mean Daily Steroid Dose at Week 52

    Time frame: Baseline (Day 0) and Week 52

    Mean daily steroid dose was calculated based on the prednisolone equivalent dose. The average dose over the 7 days prior to and including the assessment date was used as mean daily steroid dose. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value. Percent change from Baseline was calculated by dividing change from Baseline value by Baseline value and multiplying it by 100.

22. Number of Participants Who Achieved Lupus Low Disease Activity State (LLDAS) Response Criteria at Week 24

    Time frame: At Week 24

    LLDAS was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) less than equal to (<=)4 and no major active organ involvement (renal, central nervous system, cardiopulmonary, vasculitis, and pyrexia) and without hemolytic anemia or active gastrointestinal lesions; (2) no new signs or symptoms as compared to the last SELENA-SLEDAI assessment; (3) PGA score <=1 (33 millimeter); (4) corticosteroid dose <=7.5 milligram (mg)/day at time of assessment; and (5) use of the same immunosuppressant as compared with prior medication. No unapproved immunosuppressant drugs like rituximab, anifrolumab, ustekinumab, or baricitinib were used as concomitant medications.

23. Number of Participants Who Achieved LLDAS Response Criteria at Week 52

    Time frame: At Week 52

    LLDAS was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) less than equal to (<=)4 and no major active organ involvement (renal, central nervous system, cardiopulmonary, vasculitis, and pyrexia) and without hemolytic anemia or active gastrointestinal lesions; (2) no new signs or symptoms as compared to the last SELENA-SLEDAI assessment; (3) PGA score <=1 (33 millimeter); (4) corticosteroid dose <=7.5 milligram (mg)/day at time of assessment; and (5) use of the same immunosuppressant as compared with prior medication. No unapproved immunosuppressant drugs like rituximab, anifrolumab, ustekinumab, or baricitinib were used as concomitant medications.

24. Change From Baseline in Blood Levels of Anti-double-stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody at Week 24

    Time frame: Baseline (Day 0) and Week 24

    Blood samples were collected for anti-dsDNA antibody biomarker analysis. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

25. Change From Baseline in Blood Levels of Anti-dsDNA Antibody at Week 52

    Time frame: Baseline (Day 0) and Week 52

    Blood samples were collected for anti-dsDNA antibody biomarker analysis. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

26. Change From Baseline in Blood Levels of Complement Component-3 (C3) and Complement Component-4 (C4) at Week 24

    Time frame: Baseline (Day 0) and Week 24

    Blood samples were collected from participants to assess C3 and C4 levels. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

27. Change From Baseline in Blood Levels of Complement Component-3 (C3) and Complement Component-4 (C4) at Week 52

    Time frame: Baseline (Day 0) and Week 52

    Blood samples were collected from participants to assess C3 and C4 levels. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

28. Change From Baseline in Blood Levels of Complement Hemolytic Activity at 50% (CH50) at Week 24

    Time frame: Baseline (Day 0) and Week 24

    Blood samples were collected from participants to assess CH50 concentrations. CH50 is a blood test that measures the overall activity of the complement system, a group of proteins crucial for the immune system's function. Low CH50 levels can be associated with certain infections. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

29. Change From Baseline in Blood Levels of Complement Hemolytic Activity at 50% (CH50) at Week 52

    Time frame: Baseline (Day 0) and Week 52

    Blood samples were collected from participants to assess CH50 concentrations. CH50 is a blood test that measures the overall activity of the complement system, a group of proteins crucial for the immune system's function. Low CH50 levels can be associated with certain infections. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

30. Change From Baseline in Urine Protein/Creatinine Ratio at Week 24

    Time frame: Baseline (Day 0) and Week 24

    Urine samples were collected from participants to assess Urine Protein/Creatinine Ratio. It is a test that estimates how much protein is being excreted in urine, normalized to creatinine. It's commonly used to assess kidney function and detect proteinuria. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.

31. Change From Baseline in Urine Protein/Creatinine Ratio at Week 52

    Time frame: Baseline (Day 0) and Week 52

    Urine samples were collected from participants to assess Urine Protein/Creatinine Ratio. It is a test that estimates how much protein is being excreted in urine, normalized to creatinine. It's commonly used to assess kidney function and detect proteinuria. Baseline was considered as Day 0 of the study. Change from Baseline was defined as value at the indicated time point minus Baseline value.