The effectiveness and safety of biological therapeutics in juvenile-onset systemic lupus erythematosus (JSLE): a systematic review

Abstract

Objective To systematically review and summarize the available literature regarding the effectiveness and safety of biologics in the treatment of juvenile-onset systemic lupus erythematosus. Methods PubMed was systematically searched for relevant literature (2012–2017 inclusive) using the following criteria: (1) patients diagnosed with juvenile-onset systemic lupus erythematosus (≤18 years at diagnosis); (2) treatment with any biological agent; and (3) outcome measures assessing effectiveness and safety. Systematic literature reviews, meta-analyses, randomized controlled trials, cohort studies, case control studies, cross sectional surveys and case-series with ≥3 patients were included. Independent extraction of articles by two authors using predefined criteria was performed. The quality of each study was assessed using CASP tools and Oxford CEBM Levels of Evidence. Results Nine articles met inclusion criteria: six cohort studies, two case series and one pilot study, totalling 230 patients. All but one article reported the effects of rituximab, the other those of belimumab. Overall, patients had active disease refractory to standard of care regimens using corticosteroids and immunosuppressants. Available evidence for rituximab demonstrated improvements in disease activity, complement levels and anti-dsDNA titres accompanying a steroid-sparing effect. Conclusion Rituximab can be considered an effective treatment in juvenile-onset systemic lupus erythematosus patients with severe disease manifestations and/or refractory disease. Based on current evidence, use of belimumab in juvenile-onset systemic lupus erythematosus patients cannot be recommended. The long-term safety of these biological agents remains uncertain. Further prospective studies, ideally robust randomized controlled trials, are urgently needed to obtain more accurate data on the effectiveness and long-term safety of rituximab, belimumab and other biologics in juvenile-onset systemic lupus erythematosus.

A machine learning approach for precision diagnosis of juvenile-onset SLE

“…However, the efficacy of each biologic drug is unsatisfactory due to the heterogeneous immunopathogenesis [23]. For instance, the complete response (CR) rate of rituximab assessed by the British Isles Lupus Assessment Group (BILAG) was only 46.7% for SLE [32].…”

“…Precise and early diagnosis of JSLE is particularly important because morbidity and mortality can be significantly controlled with suitable treatment [23]. A recent study showed that in the UK, JSLE diagnosis based on the onset of symptoms is accomplished in a median time of two months, but there was a significant variation in diagnosis time (interquartile range 1–6 months) due to the highly heterogeneous clinical manifestation of the disease [24, 25].…”

“…The development and use of biologic therapies have been increasingly promising because they can target specific immunopathological agents and diminish SLE disease progression [31]. However, the efficacy of each biologic drug is unsatisfactory due to the heterogeneous immunopathogenesis [23]. For instance, the complete response (CR) rate of rituximab assessed by the British Isles Lupus Assessment Group (BILAG) was only 46.7% for SLE [32].…”

2020 Chinese guidelines for the diagnosis and treatment of systemic lupus erythematosus

“…For patients with refractory lupus nephritis and hematologic involvement, the disease can be controlled, and the dosage of glucocorticoids can be reduced. [98,101] Common adverse reactions include infections and infusion reactions. [98] FDA, Food and Drug Administration; CFDA, China Food and Drug Administration.…”

“…[98,101] Common adverse reactions include infections and infusion reactions. [98] FDA, Food and Drug Administration; CFDA, China Food and Drug Administration. Patients with moderate to severe SLE [74] In patients with moderate to severe lupus nephritis, mycophenolate mofetil is an effective treatment in the induction and maintenance phases, and in reducing the relapse rate.…”