Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis

Abstract

Objective Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Methods Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. Results There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0–8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6–980.3) vs. 1061.9 (534.8–1590.0 ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). Conclusions We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0–5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

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

“…Mok et al [ 24 ] reported that the prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations with serologic and clinical remission, and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares were observed. Regarding renal survival, the probabilities of developing 1ry and 2ry end-points were higher in the HCQ group at 6 and 12 months as shown by Andrade Balbi et al [ 25 ], Lee et al [ 26 ], and Pons-Estel et al [ 27 ] who revealed higher recovery of renal function and lower probability of kidney failure after 6 months of HCQ treatment. In addition, HCQ can delay the development of renal damage in LN with lower disease activity and glucocorticoid doses than in patients who did not receive HCQ [ 27 ].…”

Towards development of treat to target (T2T) in childhood-onset systemic lupus erythematosus: PReS-endorsed overarching principles and points-to-consider from an international task force

“…Antimalarial treatment is considered a quality indicator in North America,59 with a large retrospective cSLE cohort (n=473) demonstrating antimalarial treatment to be associated with protection against new damage accrual 54. Hydroxychloroquine blood levels are inversely correlated with disease activity in cSLE,96 with low concentrations predictive of flare 97. The Task Force noted hydroxychloroquine toxicity to be rare in cSLE 98.…”

Flares in Lupus Nephritis: Risk Factors and Strategies for Their Prevention

“…The Italian study by Moroni et al [ 60 ] showed that continuing HCQ after withdrawal of immunosuppressive agents was linked to reduced renal flares. Also, in a case series of pediatric LN under a prescribed HCQ dose of 4.0–5.5 mg/kg/day, a HCQ blood cut-off level under 1075 ng/mL was associated with increased flares [ 61 ]. The same trends have been described for adults with LN [ 62 ].…”