2045 HYDROXYCHLOROQUINE LEVELS DEFINE HIGH RATES
HYDROXYCHLOROQUINE LEVELS DEFINE HIGH RATES OF NON ADHERENCE
AND PREDICT WORSE RENAL OUTCOMES IN PATIENTS WITH LUPUS NEPHRITIS
Suceena Alexander1, Gary Chusney2, Vivienne D Chusney2, Janet Lee2, Tom Cairns1 and Liz
Imperial College Healthcare NHS Trust Lupus Centre and 2Leslie Brent Laboratory,
Hammersmith Hospital, London, UK
INTRODUCTION: Non adherence (NA) to lupus nephritis (LN) treatment (Rx) is the most
important factor for non-remission (NR) or renal relapses (RR). Hydroxychloroquine (HCQ) with a
long terminal half-life of >40 days is ideally positioned to identify NA based on its blood levels. We
report the utility of our newly developed HCQ assay in defining NA and poor outcomes in LN.
AIM: To identify non adherence defined as HCQBL ≤0.2mg/L and correlate with clinical outcomes
in patients with ISN/RPS Class III, IV or V lupus nephritis, at baseline and at follow up.
METHODS: 154 patients (pts) >18 years of age with ISN/RPS class III, IV or V LN and on HCQ
for at least 3 months had HCQBLs measured during treatment. Complete remission (CR) was
defined as serum creatinine (SCr) not more than 15% above baseline & urine protein:creatinine
ratio (PCR) <50mg/mmol. Renal Relapse (RR) was defined as persistent increase of >30% in
proteinuria and/ or SCr requiring renal biopsy or increase/ change in immunosuppression. Persistent
NA was defined as HCQBL ≤0.2mg/L on two separate patient clinic visits. The baseline of this
study was the date of first HCQBL testing for each patient.
RESULTS: Out of the 154 patients, 45.5% of patients were Indians and SE Asians. The baseline
demographic and clinical variables were comparable between the non-adherent and adherent
groups. The mean follow up period was 20.1±10.9 mths. The mean HCQBL dose was 5.4 ±
1.8mg/kg. 24.7% of patients were NA for HCQ and 17.3% (19/110) of them had persistent NA. CR
was significantly greater in the adherent group than the NA group at baseline (65.5% vs. 36.8%, p
<0.01) and at follow up (68.1% vs. 50%, p =0.04). HCQBL had significant AUC in the ROC curve
for detecting CR at baseline (AUC= 0.618±0.05, p =0.01). There was no significant association
between HCQBLs and occurrence of renal relapses. Intra Class Correlation (ICC) / within-patient
variability among adherent patients on HCQ 400mg/day (n = 96, total repeat measurements = 486)
was 0.7. Spearman’s correlation with mycophenolic acid trough levels at baseline and follow up (n
= 520) was significant (R2 =0.002, p <0.01).
Time to CR in all pts
Time to CR in active pts
HCQBL at baseline
Conclusions: NA for HCQ was present in approximately 25% of patients and persistent in 17.3%.
NA is significantly associated with disease activity, fewer remissions & prolonged time to CR – the
latter being a poor long term prognostic indicator with respect to renal outcomes. HCQBL had
significant area under the curve to detect CR at testing. HCQBL had a significant but weak
correlation with HCQ dose per kg. Key questions are whether NA with HCQ reflects more
generalized NA with other medications and whether HCQ levels can be used prospectively to
improve adherence and outcomes.