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Abstract Number: 1815

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence

Laura Durcan1, William Clarke2, Laurence S Magder3 and Michelle Petri1, 1Rheumatology, Johns Hopkins University Hospital, Baltimore, MD, 2Department of Pathology, Clinical Chemistry., Johns Hopkins University Hospital, Baltimore, MD, 3Epidemiology and Preventive Medicine, University of MD, Baltimore, MD

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: SLE and hydroxychloroquine

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Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Hydroxychloroquine is at the cornerstone of systemic lupus erythematosus (SLE) management. It is used for both its effect on disease activity and long-term benefits. Poor medication adherence in SLE predicts bad outcomes. One way to assess adherence is to measure blood levels. Conflicting data exist regarding hydroxychloroquine blood levels and disease activity. There is also dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. This work was undertaken, in a large lupus cohort, using sequential hydroxychloroquine blood levels to clarify these issues. 

Methods:

Patients with SLE in a longitudinal cohort were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max 400mg/day).  In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg daily.  Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Those with a sub-therapeutic level were informed and counselled on the importance of adherence. Vitamin D levels were measured and patients were prescribed 50,000 units per week if their level was below 40ng/ml. Patients were divided according to baseline blood hydroxychloroquine level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had.

Results:

The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height, BMI and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). There was a correlation between blood levels of vitamin D and hydroxychloroquine levels which increased in parallel (correlation coefficient 0.12, p<0.0022).  At first measurement, 56% had therapeutic hydroxychloroquine blood levels and by the third measurement this increased to 80% (p =<0.0001). 

Conclusion:

There was a trend towards higher disease activity with lower hydroxychloroquine levels.  We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can significantly increase adherences rates.

Table 1.  Number (%) with Various Levels of Hydroxychloroquine at the first Hydroxychloroquine Assessment by Patient Characteristics.

Characteristics 

HCQ

<15 ng/ml

HCQ

15–500 ng/ml  

HCQ

500-2000 ng/ml

HCQ

≥2000 ng/ml

P value

All (n=686)

88 (13%)

216 (31%)

366 (53%)

16 (2%)

 

Gender

 

 

 

 

0.050

 Female (n=633)

84 (13%)

206 (33%)

329 (52%)

15 (2%)

 Male (n=53)

4 (8%)

10 (19%)

38 (71%)

1 (2%)

Ethnicity

 

 

 

 

0.41

  Caucasian (n=333)

37 (11%)

104 (31%)

182 (55%)

10 (3%)

  African-American (n=287)

43 (15%)

86 (30%)

154 (54%)

4 (1%)

  Other (n=66)

8 (12%)

26 (39%)

30 (45%)

2 (3%)

Age

 

 

 

 

0.0018

  ≤30 yrs (n=89)

10 (11%)

18 (20%)

59 (66%)

2 (2%)

  30-44 yrs (n=244)

28 (11%)

98 (40%)

114 (47%)

4 (2%)

  45-59 yrs (n=230)

36 (16%)

75 (33%)

114 (49%)

6 (3%)

  60 + yrs (n=123)

14 (11%)

25 (20%)

80 (65%)

4 (3%)

Education

 

 

 

 

0.12

  Less than HS (n=51)

5 (10%)

18 (35%)

25 (49%)

3 (6%)

  High school (n=160)

30 (19%)

49 (31%)

78 (49%)

3 (2%)

  Some college (n=465)

52 (11%)

144 (31%)

259 (56%)

10 (2%)

Family income

 

 

 

 

0.54

 ≤$30,000 (n=195)

29 (15%)

59 (30%)

103 (53%)

4 (2%)

 $30,000-$60,000(n=160)

26 (16%)

47 (29%)

84 (53%)

3 (2%)

    Over $60,000 (n=316)

32 (10%)

105 (33%)

170 (54%)

9 (3%)

BMI

 

 

 

 

0.26

  <20 (n=66)

9 (14%)

20 (30%)

34 (52%)

3 (5%)

  20-24.99 (n=203)

25 (12%)

57 (28%)

114 (56%)

7 (3%)

  25-25.99 (n=185)

30 (16%)

55 (30%)

97 (52%)

3 (2%)

  30+ (n=215)

19 (9%)

79 (37%)

114 (53%)

3 (1%)

SLEDAI

 

 

 

 

0.38

  0 (n=267)

27 (10%)

83 (31%)

150 (52%)

7 (3%)

  1-3 (n=217)

32 (15%)

71 (33%)

112 (52%)

2 (1%)

  4+ (n=202)

29 (14%)

62 (31%)

104 (51%)

7 (3%)

PGA

 

 

 

 

0.37

    0 (n=193)

15 (8%)

59 (31%)

114 (59%)

5 (3%)

    >0 to 0.99  (n=301)

42 (14%)

98 (33%)

157 (52%)

4 (1%)

    1.00 to 1.49  (n=80)

14 (18%)

23 (29%)

40 (50%)

3 (4%)

    1.50-1.99  (n=56)

6 (11%)

19 (34%)

29 (52%)

2 (4%)

    2.00+  (n=48)

9 (19%)

16 (33%)

21 (44%)

2 (4%)

Vitamin D

 

 

 

 

0.011

  < 40 ng/ml (n=359)

55 (15%)

125 (35%)

170 (47%)

9 (3%)

  40+ ng/ml (n=321)

33 (10%)

89 (28%)

192 (60%)

7 (2%)

Creatinine (mg/ml)

 

 

 

 

0.029

  <1.4 (n=618)

76 (12%)

195 (32%)

334 (54%)

13 (2%)

   1.4-4.9 (n=15)

5 (33%)

4 (27%)

6 (40%)

0 (0%)

   5.0 +  (n=6)

1 (17%)

3 (50%)

1 (17%)

1 (17%)

Height (inches)

 

 

 

 

0.31

<60 (n=20)

5 (25%)

3 (15%)

11 (55%)

1 (5%)

 

60-62.5 (n=221)

22 (10%)

78 (35%)

113 (51%)

8 (4%)

 

63-67.9 (n=320)

44 (14%)

97 (30%)

174 (54%)

5 (2%)

 

68+ (n=113)

15 (13%)

33 (29%)

63 (56%)

2 (2%)

 

Ideal Body Weight

 

 

 

 

0.82

Less than (n=95)

14 (15%)

28 (29%)

50 (53%)

3 (3%)

 

Greater than (n=574)

69 (12%)

183 (32%)

309 (54%)

13 (2%)

 

HCQ= hydroxychloroquine, BMI=body mass index, SLEDAI= Systemic Lupus Erythematosus Disease Activity Index, PGA= Physician Global Assessment.


Disclosure: L. Durcan, None; W. Clarke, None; L. S. Magder, None; M. Petri, None.

To cite this abstract in AMA style:

Durcan L, Clarke W, Magder LS, Petri M. Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/hydroxychloroquine-blood-levels-in-systemic-lupus-erythematosus-clarifying-dosing-controversies-and-improving-adherence/. Accessed .
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