Hydroxychloroquine in children with proliferative lupus nephritis: a randomized clinical trial

Abstract

Hydroxychloroquine (HCQ) is an antimalarial agent used to treat mucocutaneous, musculoskeletal, constitutional manifestations of systemic lupus erythematosus (SLE). This study assessed the efficacy and side effects of HCQ in children with proliferative lupus nephritis (LN). This double-blind, randomized, placebo-controlled trial study was conducted on 60 children with proliferative LN classes III and IV treated with steroids and a mycophenolate (MMF) regimen. Patients were categorized into two groups, the HCQ group (n = 30) and the placebo group (n = 30). They were evaluated initially at 6- and a 12-month follow-up by mucocutaneous, ophthalmological examination, and investigations (BUN, creatinine, 24 h proteinuria, triglycerides (TG), cholesterol, Antids-DNA, C3, C4). Disease activity was assessed using the SLE disease activity index (SLEDAI-2 k). After 12 months, TG, cholesterol, 24 h proteinuria, Antids-DNA, and SLEDAI score were significantly decreased in the HCQ group (P: 0.002, 0.012, 0.031, 0.001, respectively). After 12 months, the cumulative probabilities of developing primary end-points (LN partial and complete remission) were 40% and 60% in the HCQ group versus 53.3% and 36.7% in the placebo group (P: 0.002). After 12 months, the HCQ group experienced mucocutaneous alopecia (3.3%), hyperpigmentation (10%), and ophthalmological mild retinal changes (6.7%), but they did not differ significantly from the placebo group. Cunclusion: HCQ improved the disease and LN activity in children with proliferative LN, with documented skin hyperpigmentation and mild retinal changes following HCQ use in a few cases. This study was registered on http://www.clinicaltrials.gov/ with trial registration number (TRN): NCT03687905, September 2018 “retrospectively registered.” What is Known: • Hydroxychloroquine (HCQ) is documented as an adjunctive treatment in children with systemic lupus erythematosus (c-SLE) LN with efficacy in improving lupus musculoskeletal and mucocutaneous manifestations. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear. What is New: • This pilot randomized clinical trial assessed the efficacy and adverse effects of HCQ in children with proliferative LN. • HCQ had numerous advantages for LN, including rapid and sustained remission, antilipidemic effect, and rapid improvement of kidney functions.

Molecular characterisation of lupus low disease activity state (LLDAS) and DORIS remission by whole-blood transcriptome-based pathways in a pan-European systemic lupus erythematosus cohort

“…These results are independent of HCQ use, a well-known modifier of TLR7 and TLR9 functions, 65 and further stress the need to globally tackle immune system activation to promote remission. Nevertheless, the use of HCQ in our population may explain the lack of association between TLR pathway signalling and renal involvement, as this drug is known to be beneficial in the treatment of lupus nephritis in conjunction with mycophenolate mofetil 66 and is recommended for all SLE patients unless contraindicated, especially those with kidney involvement. 4 67 In our analysis, BTK emerged as a potential target of downstream mediators of TLR pathway signalling.…”

Advancements on the impact of hydroxychloroquine in systemic lupus erythematosus

“…Specifically, maintaining the therapeutic concentration of HCQ has been shown to decrease the odds of flares by 26 % [ 44 ]. Moreover, HCQ has demonstrated substantial efficacy in patients with SLE and lupus nephritis (LN), including improved outcomes in children with proliferative LN [ 45 ].…”

Lupus Nephritis in Children: Novel Perspectives

“…All adult and pediatric guidelines recommend the antimalarial drug hydroxychloroquine (HCQ) for all cSLE patients, given the reduced risk of flares, end-stage kidney disease (ESKD), and death associated with its use [69,105,106]. The daily dose should be <5 mg/kg to avoid retinopathy.…”