Medi-546

Safety will be evaluated by monitoring and assessing SAEs and Non-Serious AEs as reported throughout the study and until 12 weeks after the last dose of anifrolumab

The proportion of patients who achieve DORIS remission at week 52 DORIS criteria: clinical SLEDAI (sum of all SLEDAI-2K items except for increased deoxyribonucleic acid \[DNA\] binding and low complement) =0, Physician's Global Assessment (PGA) \<0.5 (0-3), prednisolone 5 mg/day or less, and antimalarials, stable immunosuppressives, and biologics

Proportion of participants who are in DORIS remission at Week 52 will be assessed. DORIS remission is defined as Clinical SLEDAI-2K (sum of all SLEDAI-2K items except for increased deoxyribonucleic acid \[DNA\] binding and low complement) = 0; PGA \[0-3\] \< 0.5, prednisone 5 mg/day or less, and stable antimalarials, ISs, and biologics.

The CLASI is a validated index used for assessing the cutaneous lesions of SLE. It consists of 2 separate scores: i) activity of the disease, and ii) measure of damage. The CLASI instrument will be used at each study visit to capture individual skin manifestation scores. CLASI-70 responder (Yes/No) is defined as a participant who achieves a 70% reduction relative to baseline in CLASI-A score. Otherwise, the participant is considered a non-responder.

Participants who have at least moderate improvement in disease activity TIS ≥ 40 and has not met "confirmed deterioration" criteria at 2 consecutive visits

The serum concentration will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.

The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.

The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.

The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.

BICLA response is defined as: * Reduction of all baseline British Isles Lupus Assessment Group BILAG-2004 A to B/C/D and B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG- 2004 B. * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), defined as an increase from baseline of \> 0 points. * No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a Physician's Global Assessment (PGA) 3-point visual analogue scale (VAS).

Number of participants meeting all the criteria: * Improvement in at least 2 components (≥5% increase for percent predicted Forced Vital Capacity (FVC) and/or≥25% decrease for Modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment (PtGA), Clinician Global Assessment (CGA) * Worsening in no more than one component (≥5% decrease percent predicted FVC and/or≥25% increase for mRSS, HAQ-DI, PtGA, CGA) * No significant SSc-related event as defined by: New scleroderma renal crisis New decline in percent predicted FVC≥15% in established interstitial lung disease or new percent predicted FVC below 80% predicted New onset of left ventricular failure requiring treatment New onset of pulmonary arterial hypertension requiring treatment Gastrointestinal dysmotility requiring enteral or parenteral nutrition Digital ischemia with gangrene, amputation, or hospitalization requiring treatment -Otherwise, a participant is a non-responder

CRR is defined as: * UPCR ≤ 0.5 mg/mg * eGFR ≥ 60 mL/min/1.73 m2 or no decrease from baseline of ≥ 20%

Composite endpoint (BICLA),a composite binary endpoint defined by meeting all of the following criteria: * Reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined as an increase of ≥0.30 points on a 3-point PGA visual analogue scale (VAS)

BICLA response is a composite binary endpoint whereby responders are defined by meeting all of the following criteria: * Improvement from baseline in disease activity as measured by BILAG-2004. Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, where worsening is defined as ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG 2004 B. * No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of \> 0 points in SLEDAI-2K. * No worsening from baseline in the patient's lupus disease activity, where worsening is defined as an increase ≥ 0.30 points on a 3-point PGA VAS.

The event rate per 100 participant years was defined as the number of participants with an event divided by the sum of exposure time during the LTE study (including follow-up) in days for all participants in the analysis set multiplied by 365.25 days/year multiplied by 100. The exposure in a time period for each participant was calculated as end of period - start of period + 1. EAIRs of AESIs are presented as event rate per 100 participant years. The following AESIs were pre-defined: * Non-opportunistic serious infections * Opportunistic infections * Anaphylaxis * Malignancy * Herpes zoster * Tuberculosis (TB) (including latent TB) * Influenza * Vasculitis (non-systemic lupus erythematosus \[SLE\]) * Major cardiovascular events as according to the Cardiovascular Event Adjudication Committee.

EAIRs of SAEs are presented as event rate per 100 participant years. An SAE was an AE occurring during any study phase that fulfils 1 or more of the following criteria: * Results in death * Is immediately life-threatening * Requires in-patient hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions * Is a congenital abnormality or birth defect * Is an important medical event that may jeopardise the participant or may require medical intervention to prevent one of the outcomes listed above.

Composite endpoint BICLA was defined by meeting all of the following criteria: * Reduction of all baseline British Isles Lupus Assessment Group (BILAG)-2004 A to B/C/D and baseline BILAG-2004 B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K * No worsening from baseline in participants' lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) * No discontinuation of investigational product * No use of restricted medications beyond the protocol allowed threshold before assessment

SRI(4) was defined as meeting all of the following criteria: Reduction from baseline of ≥4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) No new organ systems affected, defined by 1 or more British Isles Lupus Assessment Group (BILAG-2004) A or 2 or more BILAG-2004 B items No worsening from baseline in participants lupus disease activity. Worsening was defined as an increase of ≥0.30 points on a 3-point Physician's Global Assessment (PGA) visual analogue scale (VAS) No discontinuation of investigational product and no use of restricted medications beyond the pre-specified analysis threshold.

The HiSCR is a validated assessment tool developed for patients with hidradenitis suppurativa. It is a dichotomized clinical response assessment that measures the status of three types of lesions: abscesses, inflammatory nodules, and draining fistulas. HiSCR 50 is defined as participants who have at least a 50% reduction in abscess and nodule count compared to baseline and no increase in the number of abscesses or draining tunnels.

To characterize PK (Cmax) of anifrolumab in pediatric participants with SLE following SC administration.

To characterize PK (AUC) of anifrolumab in pediatric participants with SLE following SC administration.

To characterize PK (tmax) of anifrolumab in pediatric participants with SLE following SC administration.

To characterize PK (CL/F) of anifrolumab in pediatric participants with SLE following SC administration.

To characterize PK (Ctrough,ss) of anifrolumab in pediatric participants with SLE following SC administration.

Maximum concentration (Cmax) of anifrolumab is based on sample collected 5 to 8 days after the first dose of strudy treatment.

Steady-state serum through concentration (Ctrough) is based on sample collected at Week 12 prior to dosing of study treatment (predose).

21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. Levels of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control.

21-gene type I IFN signature score (fold change) is based on samples collected both at baseline and Week 12 prior to dosing of study treatment. For each individual participant and assessment, the level of 21-gene type I IFN pharmacodynamics signature is derived as relative to a pooled normal control, as the median of 100-(((baseline-Week 12)/baseline)\*100) for the 21 genes. At a population level, the results are presented as mean the above.

To evaluate the efficacy of anifrolumab plus SOC (combination of mycophenolate mofetil and corticosteroids) compared with placebo plus SOC in subjects with active proliferative lupus nephritis (LN). Geometric mean ratio of 24-hour UPCR at week 52 over baseline. Values \<1 indicate improvement from baseline.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with DAEs are reported.

An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported.

An SRI (4) responder defined as a participant who had 1) a reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (\>=) 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index 'A' organ system score and no more than one new or worsening BILAG-2004 Index 'B' organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.

Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. The blood samples collected were to be used to prospectively identify participants as IFN test-high or test-low. The results of this test were used to stratify participants. An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of \>= 4 points; 2) no worsening of disease from baseline as measured by the Physician Global Assessment (MDGA) (worsening was defined as an increase of \>= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 \[less than 10 mg/day and less or equal to the dose received on Day 1\]. SRI was analyzed by a logistic regression model.

To characterise the PK exposure of SC or IV anifrolumab.

To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.

To characterise the pharmacokinetic (PK) profile of anifrolumab via intravenous (IV) infusion.