Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Factors Associated with Low Blood Concentration of Hydroxychloroquine in 523 Patients with Systemic Lupus Erythematosus: Data from the PLUS Study.
Piette2, Jean-Charles, Amoura2, Zahir, The Investigators of the PLUS Study, , Musset2, Lucile, Lechat2, Philippe, Hulot2, Jean-Sébastien, Leroux2, Gaelle
We have previously demonstrated that low whole-blood Hydroxychloroquine concentration [HCQ] is a marker for and predictor of systemic lupus erythematosus (SLE) flares . The French multicenter randomized PLUS study (NCT 00413361) is currently assessing the potential benefits of individualized HCQ dosing schedules aimed at maintaining the [HCQ] above 1,000 ng/ml in SLE patients. According to the design of PLUS study, all patients have a measurement of [HCQ]. We studied the relationship between [HCQ] and epidemiological data at baseline.
Among the 569 included in the PLUS study, 523 patients who were treated with the same dose of HCQ (400 mg/d) were studied. [HCQ] was measured at the time of inclusion, and the patients were divided into 2 groups according to their [HCQ]: group A ([HCQ] < 750 ng/ml), and group B ([HCQ]>= 750).
The following parameters were similar between group A (179 patients) and group B (344 patients): mean age and duration of SLE, current smoking status, family history of SLE, frequency of associated antiphospholipid syndrome, values of C3, anti-nucleosome antibodies and anti-DNA antibodies, % of patients treated with immunosuppressive drugs, and mean daily dose of prednisone
In group A (low [HCQ]), the % of men (14.6 vs 6.2, p=0.004), weight (69±15 vs 62±12 kg, p<0.0001), BMI (25.4±4.2 kg/m2 vs 23.2±5.3; p<0.001) and estimated creatinine clearance (114±35 vs 99±29 ml/min; p<0.0001) were significantly higher compared to group B. After exclusion of men, the difference remained significant for weight and creatinine clearance.
At inclusion, 106 patients in group A (58%) were treated with steroids vs 238 in group B (69%, p = 0.02). Adherence to the prescription of HCQ assessed by the investigator on a VAS (from 0 to 10) was significantly lower in group A (8.99±1.3) compared to group B (9.3±1.03, p=0.003). Even though patients were excluded if they had a SLEDAI > 12, we found a significantly higher SLE activity in group A (mean SLEDAI: 2.41±2.5 vs 1.88±2.34, p = 0.016). This difference held on even in the subset of patients treated with steroids (2.94 ± 2.62 vs 2.16±2.54, p=0.019). Platelet counts were significantly lower in group A (225,000± 75,000 vs. 268,000±71,000/mm3, p<0.0001).
In multivariate analysis, factors associated with low [HCQ] were low level of platelets (p<0.0001), high clearance of creatinine (p<0.001), absence of treatment with steroids (p=0.003), poor adherence (p=0.003), high BMI (p=0.007) and SLE activity (p=0.024).
This preliminary analysis confirms in a new set of patients our previously reported association of low [HCQ] with a higher SLE activity . This was not expected given that patients included in PLUS study have low SLE activity according to inclusion criteria. Other parameters associated with low [HCQ] included high BMI, poor adherence assessed by the investigator, low platelet count, and high estimated creatinine clearance.
To cite this abstract, please use the following information:
Piette, Jean-Charles, Amoura, Zahir, The Investigators of the PLUS Study, , Musset, Lucile, Lechat, Philippe, Hulot, Jean-Sébastien, et al; Factors Associated with Low Blood Concentration of Hydroxychloroquine in 523 Patients with Systemic Lupus Erythematosus: Data from the PLUS Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2239