Background/Purpose: Renal involvement is reported in up to 80% of juvenile systemic lupus erithematosus (JSLE) and its among the most severe manifestations in these population. Antimalarials are one of the cornerstones of lupus treatment with beneficial effects in maintenance of disease remission. In fact, low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus patients. The aim of this study is to determine the HCQ cut-off levels which predicts flare and to assess the adherence pattern by overall blood HCQ concentration in juvenile lupus nephritis (LN) patients.

Methods: Juvenile LN patients under the prescribed HCQ 2016-American Academy Ophtalmology (AAO) recommended dose for at least six months were prospectively followed. Participants were evaluated at baseline (BL) and 6-months for clinical, laboratorial data and HCQ blood levels (high-performance liquid chromatography-tandem mass spectrometry). Disease flare was defined as increase ≥3 in SLEDAI-2K and/or increase in immunosuppressive/glucocorticoid.

Results: Sixty JSLE patients, 80% female, mean age of 16.6 ± 3.13 years and mean disease duration of 5.5 ± 3.65 years were included. Nineteen patients (32%) evolved with disease activity after 5.8 (1.6 – 9.8) months. Participants with flare presented a lower BL median HCQ blood level compared to stable patients [557.5 (53.5 – 2137.8) ng/ml vs. 1061.9 (53.5 – 2137.8) ng/ml, p=0.009]. There were no differences in demographic data, disease parameters and concomitant treatment in both groups. A ROC curve analysis demonstrated a BL blood HCQ cut-off level of 573.45 ng/ml as predictor of disease reactivation, with an OR=3.75 (95%CI 1.19-11.76, p=0.023) for flare (Table 1).  Flare frequencies were lower in patients with adequate BL HCQ blood levels ( > 573 ng/ml) compared to those with inadequate levels (≤ 573 ng/ml) (21% vs. 50%, p=0.042). A prospective 6-months blood HCQ monitoring was performed in 54 patients, demonstrating an overall stable pattern from baseline to the final evaluation in McNemar’s analysis (p=0.359) with most patients (57%) presenting fluctuating/ persistently low levels (≤573 ng/ml). Among those with persistently inadequate HCQ pattern (n=12) half activated disease during this period. The higher frequency of flares in patients with persistently low HCQ levels vs. persistently adequate (50% vs. 26%, p=0.260) or vs. fluctuating levels (50% vs. 26%, p=0.255) did not reach statistical significance.

Conclusion: In conclusion, we demonstrated for the first time that HCQ blood cut-off level of 573 ng/ml predicts 6-months flare in juvenile lupus nephritis patients under prescribed HCQ 2016-AAO dose. 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. (Clinicaltrials.gov number #NCT03122431).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxychloroquine-blood-levels-predicts-6-months-disease-activity-in-juvenile-lupus-nephritis/