Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Results of a French Multicenter Randomized Prospective Study (the PLUS Study) on Reduction of Systemic Lupus Erythematosus Flares Through Adaptation of the Dosage of Hydroxychloroquine to Its Whole-Blood Concentration.

Costedoat-Chalumeau1,  Nathalie, Galicier1,  L., Aumaitre1,  O., Frances1,  C., Le Guern2,  Véronique, Liote1,  F., Smail1,  A.

CHU Pitié-Salpêtrière, Paris, France
Cochin Hospital, Paris, France
CHU poitiers, Poitiers, France

Background/Purpose:

Blood Hydroxychloroquine concentration [HCQ] varies widely among patients. We have previously demonstrated that low blood HCQ concentration [HCQ] is a marker for and a predictor of systemic lupus erythematosus (SLE) flares [Costedoat-Chalumeau, Arthritis Rheum, 2006]. These findings led us to perform a prospective study to determine the potential benefits of individualizing HCQ dosing schedules aimed at maintaining the [HCQ]· 1000 ng/ml.

Methods:

SLE patients treated with HCQ for at least 6 months, with stable disease and a SELENA-SLEDAI <=12, and without neither known retinopathy nor suspected non adherence, were included in this randomized, double-blind, placebo-controlled, multicenter (n=37) trial and had a centralised [HCQ] dosage. Patients with [HCQ] ranging between 100 and 750 ng/ml were eligible for randomisation between no daily dosage change (group 1) and increased HCQ dosage to obtain a [HCQ]· 1000 ng/ml (group 2). All randomised patients received 4 tablets/day (including HCQ and placebo), and were followed-up at 1, 3, 5, and 7 months.

Results:

573 subjects were included. At day 0, the median SLEDAI was 2.02 ± 2.4. The median [HCQ] was 857 [0–3316] ng/ml. There was an inverse correlation between [HCQ] and disease activity measured by SELENA-SLEDAI (p=0.023).

10 patients were excluded for major non-adherence ([HCQ]<100 ng/ml), 354 had early study discontinuation ([HCQ]>750 ng/ml), and 209 were eligible for randomisation (100< [HCQ] <750 ng/ml). 33 patients were not randomised due to patient refusal (n=11), contra-indications (ophthalmological n=8, and renal insufficiency n=1), SLE flares between inclusion and randomization (n=4), non-adherence recognition (n=4), pregnancy (n=2) or other causes (n=3). 5 dropped out just after randomization. Then, 171 patients were analyzed.

Median [HCQ] significantly increased between inclusion and randomisation (548 [102–749] to 613 [35–2005]; P<0,001), meaning before any therapeutic action. Median [HCQ] were similar between group 1 (n = 84) and group 2 (n = 87) at randomization (623 [193–1610] versus 591 [35–2005]; p = 0.2), and were significantly higher in group 2 at M1 (1250 [9–3253] vs 733 [185–1700]; p<0.001), M3 (1362 [44–4005] vs 661 [239–1797]; p <0.001), M5 (1428 [33–3282] vs 718 [194–2013]; p <0.001) and M7 (1271 [13–3311] vs 665 [80–1578]; p <0.001).

The number of SLE flares was similar in both groups (26.2% vs 27.6%; p = 0.83). Many patients in group 1 had [HCQ] in the therapeutic range and conversely, XXX patients in group 2 had low [HCQ]. When we mixed both groups, the comparison of patients with [HCQ] < 1000 and those with [HCQ]· 1000 during the 7 months of follow-up showed a rate of SLE flares of 18/53 (34%) and 8/36 (22%) respectively (p=0.23).

Conclusion:

We confirm that low [HCQ] is associated with higher SLE activity. We failed to demonstrate that the adaptation of HCQ dosage reduces SLE flares in patients with low [HCQ]. However, the knowledge of low [HCQ] and the inclusion in the study improved treatment adherence, allowing many patients to reach higher [HCQ]. Patients with higher [HCQ] during the study had a trend toward a reduction of SLE flares although not statistically significant.

ClinicalTrials.gov: NCT00413361

To cite this abstract, please use the following information:
Costedoat-Chalumeau, Nathalie, Galicier, L., Aumaitre, O., Frances, C., Le Guern, Véronique, Liote, F., et al; Results of a French Multicenter Randomized Prospective Study (the PLUS Study) on Reduction of Systemic Lupus Erythematosus Flares Through Adaptation of the Dosage of Hydroxychloroquine to Its Whole-Blood Concentration. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :608
DOI:

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