Pharmacological Management of Childhood-Onset Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.

Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus: A Review of the Literature

“…Antimalarial drugs, such as hydroxychloroquine, are usually used as first-line drugs combined with systemic corticosteroids if the patient needs systemic therapy. However, these drugs can be used as a monotherapy in mild cases of JSLE with mucocutaneous manifestations (e.g., malar rash, discoid rash, photosensitivity, including oral ulcers) [ 63 , 64 ]. Complete blood counts, eye examination and liver function tests should be monitored, as drug toxicities may occur in children.…”

Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide

“…CPA is a commonly used chemotherapy drug in cancer treatment for both solid and hematological malignancies, including breast cancer, bone cancer, soft tissue sarcomas, Hodgkin's and non-Hodgkin's lymphomas and leukemia (Petrillo et al 2011). CPA is often the first-line treatment for patients with autoimmune diseases such as systemic lupus erythematosus (SLE) (Thorbinson et al 2016). CPA has a range of off-target effects, including damage to the bladder, immunosuppression, alopecia and amenorrhea related to ovarian follicle depletion (Fraiser et al 1991, Chemaitilly et al 2006, Hudson 2010.…”

Clinical trials in children and adolescents with systemic lupus erythematosus: methodological aspects, regulatory landscape and future opportunities

“…There is agreement among paediatric rheumatologists regarding principles of therapeutic and disease monitoring standards for cSLE 64 65. This is relevant for the design of cSLE trials, together with current principles of off-label medication use and standards of medical care 66–68. Regulatory agencies support the enrolment of adolescent patients with cSLE in adult SLE trials.…”