RARE DISEASE
Pediatric systemic lupus erythematosus
Pediatric systemic lupus erythematosus
Pediatric systemic lupus erythematosus
Synonyms: SLE, pediatric onset
Synonyms: SLE, pediatric onset
Synonyms: SLE, pediatric onset
Drug discovery
2
drugs
With orphan designations
Overview
Pediatric systemic lupus erythematosus (SLE) is a severe, chronic autoimmune disease characterized by multisystem inflammation and organ damage, with onset before age 18. It involves immune dysregulation, leading to autoantibody production and inflammatory tissue injury. Compared to adult-onset SLE, pediatric cases are more aggressive, with higher rates of renal, neuropsychiatric, and hematologic involvement [1][6][9].
Burden
Therapies
Hydroxychloroquine as baseline therapy [18], combined with immunosuppressants (mycophenolate, cyclophosphamide) and glucocorticoids [3][13]. Biologics (belimumab, rituximab) and calcineurin inhibitors are used for refractory cases [8][13][18]. Treatment emphasizes early remission and minimizing steroid toxicity [8][18].
Categories: rare neurological diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
1,106 drug discovery papers about Pediatric systemic lupus erythematosus, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,106 drug discovery papers about Pediatric systemic lupus erythematosus, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-15 | Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases.
DNASE1L3 deficiency is a rare autosomal-recessive monogenic form of systemic lupus erythematosus, characterized by defective clearance of extracellular DNA, leading to immune-complex formation, autoantibody production, and systemic inflammation. While early-onset lupus nephritis and hypocomplementemic urticarial vasculitis are hallmark features, the full clinical spectrum remains incompletely understood, particularly in pediatric populations. We report 4 cases from 2 unrelated consanguineous Syrian families, including 1 genetically confirmed case with a pathogenic DNASEI L3 variant, 1 case harboring a homozygous DNASEI L3 variant of uncertain significance, and 2 phenotypically concordant siblings without genetic testing. Clinical, laboratory, and histopathologic data were reviewed to characterize disease manifestations, organ involvement, serologic profiles, and therapeutic outcomes. All patients presented with recurrent fever, cutaneous rash, and musculoskeletal involvement, with notable variability in autoantibody profiles, renal pathology, and disease severity. Genetic analysis identified a homozygous pathogenic DNASEI L3 variant in case 3 and a homozygous DNASEI L3 variant of uncertain significance in case 1, supporting a clinically suspected DNASEI L3-associated monogenic lupus-spectrum disease. Renal involvement ranged from IgA glomerulonephritis to class IV lupus nephritis. Ocular manifestations, including conjunctival congestion and papilledema, were observed in 3 patients, highlighting an underrecognized feature. Therapeutic responses varied: 1 patient remained stable on baricitinib, while 2 patients succumbed to severe neurologic or renal complications. This series underscores the heterogeneous phenotypic spectrum of DNASEI L3-associated disease, including atypical seronegative presentations and diverse renal pathology. DNASEI L3-associated disease should be considered in children with early-onset vasculitic rash, hypocomplementemia, and nephritis, regardless of classical autoantibody status. Our cases expand the known clinical spectrum, emphasize the potential for ocular involvement, and suggest a role for targeted therapies such as JAK inhibitors in interferon-driven disease. Early genetic testing is essential for timely diagnosis and management of this potentially life-threatening condition.
2026-08-14 | Interferon-targeted therapy with anifrolumab in monogenic pediatric systemic lupus erythematosus due to C1q deficiency: a case report.
Monogenic Pediatric systemic lupus erythematosus (SLE) secondary to complement deficiencies, including C1Q deficiency caused by C1QA mutations, is a rare and severe type of SLE that can be characterized by early onset and refractory disease. Inhibiting the interferon pathway has proved to be an effective treatment option, although there is little evidence in monogenic pediatric SLE. We describe a 10-year-old female with genetically-verified C1Q deficiency who had persistent and severe mucocutaneous disease, with recurrent skin rash, ulcerations, and oral sores, despite long-term immunosuppressive and biologic treatment. After a disease flare, the patient was started on anifrolumab, a monoclonal antibody against type I interferon receptor. She showed significant clinical improvement and full recovery of mucocutaneous lesions, restoration of laboratory parameters and successful discontinuation of corticosteroids after the seventh monthly infusion. It was well tolerated with no serious side effects. The case demonstrates the possible effectiveness and safety of anifrolumab in the treatment of refractory cutaneous manifestations in children with monogenic pediatric SLE, which is linked to interferon pathway dysregulation. Further studies are needed to establish its role in this population.
2026-08-12 | Achievement of real-world adapted DORIS remission targets among patients with systemic lupus erythematosus initiating belimumab in the USA: A retrospective, observational, cohort study.
IntroductionRemission is a key treatment goal associated with improved patient outcomes in systemic lupus erythematosus (SLE), often measured by Definition of Remission In SLE (DORIS) criteria. In a post hoc analysis of clinical trial data, belimumab, a B-cell modulator targeting the central immunopathogenic pathway in SLE, plus standard therapy, improved DORIS remission rates versus placebo plus standard therapy; however, US real-world remission rates remain limited. Measuring DORIS criteria in real-world clinical practice is challenging because required variables, particularly the SLE Disease Activity Index (SLEDAI) component, are often unavailable or incompletely recorded. Therefore, we evaluated an adapted DORIS definition for real-world datasets and examined predictors of remission among US patients initiating belimumab.MethodsThis retrospective observational cohort study analysed data for patients with SLE initiating belimumab from the OM1 PremiOM™ SLE dataset, comprising electronic health records/healthcare claims data (2013-2024) for patients with SLE. The primary outcome was probability of achieving adapted DORIS remission at 28, 48, and 52 weeks post-treatment initiation, defined as clinician-recorded SLEDAI (crSLEDAI) or estimated SLEDAI (eSLEDAI) = 0, Physician Global Assessment (PGA) <2 on a 0-10 numerical rating scale, and prednisone-equivalent dose ≤5 mg/day. Kaplan-Meier estimates provided remission probabilities and logistic regression identified predictors of remission.ResultsMost patients (N = 398) were White, female, from the Southern region of the USA, and had commercial insurance. The probability of achieving adapted DORIS remission reached 28.3% (95% confidence interval: 19.8-35.9) by 52 weeks post-belimumab initiation. Older patients (≥50 years), non-White individuals, and patients with cr/eSLEDAI ≤5 demonstrated slightly higher remission probabilities than their counterparts; however, estimates differed by censoring approach, and confidence bounds overlapped. Adjusted multivariable analysis confirmed increasing age, non-White race, and cr/eSLEDAI ≤5 as significant predictors of remission.ConclusionThis study demonstrates the application of an adapted DORIS definition to large real-world observational datasets. The probability of adapted DORIS remission in US patients initiating belimumab was similar to rates reported in observational studies outside the USA, supporting the real-world effectiveness of belimumab. The increased likelihood of remission in patients with cr/eSLEDAI ≤5 supports the benefits of initiating belimumab treatment early in the disease course.
2026-08-11 | Free mycophenolic acid exposure for therapeutic drug monitoring in paediatric lupus nephritis: associations with treatment response and haematologic toxicity.
This study aimed to evaluate the associations of free mycophenolic acid (f-MPA) concentration and total MPA (t-MPA) concentration with treatment response and haematologic toxicity and to determine whether f-MPA provides additional safety-related value for therapeutic drug monitoring (TDM) in patients with paediatric lupus nephritis (LN) treated with mycophenolate mofetil (MMF). Sixty-five patients with paediatric LN receiving MMF were prospectively enrolled. The t-MPA and f-MPA were measured simultaneously using validated ultrafiltration and LC-MS/MS. Full pharmacokinetic profiles were obtained over 12 hours, and area under the concentration-time curve (AUC) was calculated for t-MPA (t-MPA-AUC) and f-MPA (f-MPA-AUC). Univariate analysis identified factors influencing efficacy (relapse-free survival) and adverse drug reaction (ADR) over 12 months. Receiver operating characteristic (ROC) curves established predictive thresholds and Kaplan-Meier methods analysed time-to-event. The 12-month relapse-free rate was 78.7% (95% CI 66.6% to 90.9%). Both t-MPA-AUC and f-MPA-AUC significantly correlated with relapse-free survival (ROC AUC 0.70 each; optimal thresholds: t-MPA-AUC=31.63 µg·h/mL, f-MPA-AUC=354.45 ng·h/mL). The average remission duration above these thresholds was 10.88 and 11.00 months. The overall MMF-related ADR incidence was 25.2%, including 17 haematological events (26.2%). The t-MPA-AUC, f-MPA-AUC, glucose, β2-microglobulin and C3 were haematological ADR risk factors. The f-MPA-AUC independently predicted haematological ADRs (optimal threshold: 492.96 ng·h/mL; specificity 86.2%). Both t-MPA-AUC and f-MPA-AUC effectively predict MMF efficacy in paediatric LN. However, f-MPA-AUC demonstrates superior predictive value for safety outcomes, specifically haematological ADRs. This supports f-MPA as a potentially better TDM metric for optimising MMF therapy safety in this population.
2026-08-08 | Subcutaneous Belimumab Demonstrates Consistent Steady-State Pharmacokinetics and is Well Tolerated in Paediatric Patients with SLE in China: An Open-Label Study.
This study assessed pharmacokinetics and safety of subcutaneous (SC) belimumab in Chinese paediatric patients with systemic lupus erythematosus (cSLE) who previously received intravenous (IV) belimumab; only the IV form is approved for cSLE in China. This single-arm, open-label, 12-week bridging study (GSK Study 217091) characterised belimumab 200 mg SC exposure in Chinese paediatric patients (5-17 years) with cSLE who completed the 48-week IV belimumab Phase 4 trial (GSK Study 213560). Safety and tolerability of SC belimumab on-treatment and in a 16-week follow-up period were also assessed. Patients were categorised based on weight; data were summarised using descriptive statistics. Overall, 16 patients were enrolled (≥ 15- < 30 kg, n = 1; ≥ 30- < 50 kg, n = 5; ≥ 50 kg, n = 10) with a mean age of 12.9 years. The geometric mean approximate Cmax (3 days post-administration) after the first and last dose were 92.44, 63.41 and 68.87 μg/mL, and 28.01, 85.11 and 88.61 μg/mL for the three weight groups, respectively. The geometric mean Ctrough at steady state were, 20.44, 71.57 and 85.55 μg/mL for the ≥ 15- < 30 kg, ≥ 30- < 50 kg and ≥ 50 kg weight groups, respectively. Thirteen patients (81%) reported ≥ 1 AE. No SAEs, severe AEs, AESIs, AEs resulting in belimumab discontinuation, deaths, or local injection site reactions were reported. SC belimumab demonstrated expected steady-state exposure and tolerability in Chinese paediatric patients with SLE, supporting its use in this patient population. GSK Study 217091; NCT05917288.
2026-08-15 | Expanding the clinical spectrum of DNASE1L3-associated monogenic lupus: A case series of 4 syrian pediatric cases.
DNASE1L3 deficiency is a rare autosomal-recessive monogenic form of systemic lupus erythematosus, characterized by defective clearance of extracellular DNA, leading to immune-complex formation, autoantibody production, and systemic inflammation. While early-onset lupus nephritis and hypocomplementemic urticarial vasculitis are hallmark features, the full clinical spectrum remains incompletely understood, particularly in pediatric populations. We report 4 cases from 2 unrelated consanguineous Syrian families, including 1 genetically confirmed case with a pathogenic DNASEI L3 variant, 1 case harboring a homozygous DNASEI L3 variant of uncertain significance, and 2 phenotypically concordant siblings without genetic testing. Clinical, laboratory, and histopathologic data were reviewed to characterize disease manifestations, organ involvement, serologic profiles, and therapeutic outcomes. All patients presented with recurrent fever, cutaneous rash, and musculoskeletal involvement, with notable variability in autoantibody profiles, renal pathology, and disease severity. Genetic analysis identified a homozygous pathogenic DNASEI L3 variant in case 3 and a homozygous DNASEI L3 variant of uncertain significance in case 1, supporting a clinically suspected DNASEI L3-associated monogenic lupus-spectrum disease. Renal involvement ranged from IgA glomerulonephritis to class IV lupus nephritis. Ocular manifestations, including conjunctival congestion and papilledema, were observed in 3 patients, highlighting an underrecognized feature. Therapeutic responses varied: 1 patient remained stable on baricitinib, while 2 patients succumbed to severe neurologic or renal complications. This series underscores the heterogeneous phenotypic spectrum of DNASEI L3-associated disease, including atypical seronegative presentations and diverse renal pathology. DNASEI L3-associated disease should be considered in children with early-onset vasculitic rash, hypocomplementemia, and nephritis, regardless of classical autoantibody status. Our cases expand the known clinical spectrum, emphasize the potential for ocular involvement, and suggest a role for targeted therapies such as JAK inhibitors in interferon-driven disease. Early genetic testing is essential for timely diagnosis and management of this potentially life-threatening condition.
2026-08-14 | Interferon-targeted therapy with anifrolumab in monogenic pediatric systemic lupus erythematosus due to C1q deficiency: a case report.
Monogenic Pediatric systemic lupus erythematosus (SLE) secondary to complement deficiencies, including C1Q deficiency caused by C1QA mutations, is a rare and severe type of SLE that can be characterized by early onset and refractory disease. Inhibiting the interferon pathway has proved to be an effective treatment option, although there is little evidence in monogenic pediatric SLE. We describe a 10-year-old female with genetically-verified C1Q deficiency who had persistent and severe mucocutaneous disease, with recurrent skin rash, ulcerations, and oral sores, despite long-term immunosuppressive and biologic treatment. After a disease flare, the patient was started on anifrolumab, a monoclonal antibody against type I interferon receptor. She showed significant clinical improvement and full recovery of mucocutaneous lesions, restoration of laboratory parameters and successful discontinuation of corticosteroids after the seventh monthly infusion. It was well tolerated with no serious side effects. The case demonstrates the possible effectiveness and safety of anifrolumab in the treatment of refractory cutaneous manifestations in children with monogenic pediatric SLE, which is linked to interferon pathway dysregulation. Further studies are needed to establish its role in this population.
2026-08-12 | Achievement of real-world adapted DORIS remission targets among patients with systemic lupus erythematosus initiating belimumab in the USA: A retrospective, observational, cohort study.
IntroductionRemission is a key treatment goal associated with improved patient outcomes in systemic lupus erythematosus (SLE), often measured by Definition of Remission In SLE (DORIS) criteria. In a post hoc analysis of clinical trial data, belimumab, a B-cell modulator targeting the central immunopathogenic pathway in SLE, plus standard therapy, improved DORIS remission rates versus placebo plus standard therapy; however, US real-world remission rates remain limited. Measuring DORIS criteria in real-world clinical practice is challenging because required variables, particularly the SLE Disease Activity Index (SLEDAI) component, are often unavailable or incompletely recorded. Therefore, we evaluated an adapted DORIS definition for real-world datasets and examined predictors of remission among US patients initiating belimumab.MethodsThis retrospective observational cohort study analysed data for patients with SLE initiating belimumab from the OM1 PremiOM™ SLE dataset, comprising electronic health records/healthcare claims data (2013-2024) for patients with SLE. The primary outcome was probability of achieving adapted DORIS remission at 28, 48, and 52 weeks post-treatment initiation, defined as clinician-recorded SLEDAI (crSLEDAI) or estimated SLEDAI (eSLEDAI) = 0, Physician Global Assessment (PGA) <2 on a 0-10 numerical rating scale, and prednisone-equivalent dose ≤5 mg/day. Kaplan-Meier estimates provided remission probabilities and logistic regression identified predictors of remission.ResultsMost patients (N = 398) were White, female, from the Southern region of the USA, and had commercial insurance. The probability of achieving adapted DORIS remission reached 28.3% (95% confidence interval: 19.8-35.9) by 52 weeks post-belimumab initiation. Older patients (≥50 years), non-White individuals, and patients with cr/eSLEDAI ≤5 demonstrated slightly higher remission probabilities than their counterparts; however, estimates differed by censoring approach, and confidence bounds overlapped. Adjusted multivariable analysis confirmed increasing age, non-White race, and cr/eSLEDAI ≤5 as significant predictors of remission.ConclusionThis study demonstrates the application of an adapted DORIS definition to large real-world observational datasets. The probability of adapted DORIS remission in US patients initiating belimumab was similar to rates reported in observational studies outside the USA, supporting the real-world effectiveness of belimumab. The increased likelihood of remission in patients with cr/eSLEDAI ≤5 supports the benefits of initiating belimumab treatment early in the disease course.
2026-08-11 | Free mycophenolic acid exposure for therapeutic drug monitoring in paediatric lupus nephritis: associations with treatment response and haematologic toxicity.
This study aimed to evaluate the associations of free mycophenolic acid (f-MPA) concentration and total MPA (t-MPA) concentration with treatment response and haematologic toxicity and to determine whether f-MPA provides additional safety-related value for therapeutic drug monitoring (TDM) in patients with paediatric lupus nephritis (LN) treated with mycophenolate mofetil (MMF). Sixty-five patients with paediatric LN receiving MMF were prospectively enrolled. The t-MPA and f-MPA were measured simultaneously using validated ultrafiltration and LC-MS/MS. Full pharmacokinetic profiles were obtained over 12 hours, and area under the concentration-time curve (AUC) was calculated for t-MPA (t-MPA-AUC) and f-MPA (f-MPA-AUC). Univariate analysis identified factors influencing efficacy (relapse-free survival) and adverse drug reaction (ADR) over 12 months. Receiver operating characteristic (ROC) curves established predictive thresholds and Kaplan-Meier methods analysed time-to-event. The 12-month relapse-free rate was 78.7% (95% CI 66.6% to 90.9%). Both t-MPA-AUC and f-MPA-AUC significantly correlated with relapse-free survival (ROC AUC 0.70 each; optimal thresholds: t-MPA-AUC=31.63 µg·h/mL, f-MPA-AUC=354.45 ng·h/mL). The average remission duration above these thresholds was 10.88 and 11.00 months. The overall MMF-related ADR incidence was 25.2%, including 17 haematological events (26.2%). The t-MPA-AUC, f-MPA-AUC, glucose, β2-microglobulin and C3 were haematological ADR risk factors. The f-MPA-AUC independently predicted haematological ADRs (optimal threshold: 492.96 ng·h/mL; specificity 86.2%). Both t-MPA-AUC and f-MPA-AUC effectively predict MMF efficacy in paediatric LN. However, f-MPA-AUC demonstrates superior predictive value for safety outcomes, specifically haematological ADRs. This supports f-MPA as a potentially better TDM metric for optimising MMF therapy safety in this population.
2026-08-08 | Subcutaneous Belimumab Demonstrates Consistent Steady-State Pharmacokinetics and is Well Tolerated in Paediatric Patients with SLE in China: An Open-Label Study.
This study assessed pharmacokinetics and safety of subcutaneous (SC) belimumab in Chinese paediatric patients with systemic lupus erythematosus (cSLE) who previously received intravenous (IV) belimumab; only the IV form is approved for cSLE in China. This single-arm, open-label, 12-week bridging study (GSK Study 217091) characterised belimumab 200 mg SC exposure in Chinese paediatric patients (5-17 years) with cSLE who completed the 48-week IV belimumab Phase 4 trial (GSK Study 213560). Safety and tolerability of SC belimumab on-treatment and in a 16-week follow-up period were also assessed. Patients were categorised based on weight; data were summarised using descriptive statistics. Overall, 16 patients were enrolled (≥ 15- < 30 kg, n = 1; ≥ 30- < 50 kg, n = 5; ≥ 50 kg, n = 10) with a mean age of 12.9 years. The geometric mean approximate Cmax (3 days post-administration) after the first and last dose were 92.44, 63.41 and 68.87 μg/mL, and 28.01, 85.11 and 88.61 μg/mL for the three weight groups, respectively. The geometric mean Ctrough at steady state were, 20.44, 71.57 and 85.55 μg/mL for the ≥ 15- < 30 kg, ≥ 30- < 50 kg and ≥ 50 kg weight groups, respectively. Thirteen patients (81%) reported ≥ 1 AE. No SAEs, severe AEs, AESIs, AEs resulting in belimumab discontinuation, deaths, or local injection site reactions were reported. SC belimumab demonstrated expected steady-state exposure and tolerability in Chinese paediatric patients with SLE, supporting its use in this patient population. GSK Study 217091; NCT05917288.
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Drug Discovery Landscape
2 orphan drug designations for Pediatric systemic lupus erythematosus.
2 orphan drug designations for Pediatric systemic lupus erythematosus.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
baricitinib | small molecules | FDA | 2017-11-02 | — | Eli Lilly and Company |
ustekinumab | antibodies | FDA | 2017-07-18 | — | Janssen Biotech, Inc. |
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