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Abstract Number: 2253

Cardiovascular Disease, Other Purported Risk Factors, and Allopurinol-Associated Severe Cutaneous Adverse Reactions: A General Population-Based Cohort Study

Na Lu1, Chio Yokose2, Hui Xie1,3, Gloria Li1, Sharan K. Rai4,5, Seoyoung C. Kim6 and Hyon K. Choi2, 1Arthritis Research Canada, Richmond, BC, Canada, 2Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, 3Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada, 4Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, 5Graduate School of Arts and Sciences, Harvard University, Cambridge, MA, 6Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Adverse events, Allopurinol, drug safety, Gout and uric acid

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Session Information

Date: Tuesday, October 23, 2018

Title: Metabolic and Crystal Arthropathies – Basic and Clinical Science Poster II

Session Type: ACR Poster Session C

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

Background/Purpose: A recent US Medicaid study found that in addition to certain races (Asians and Blacks), older age, female sex, chronic kidney disease (CKD), and initial allopurinol dose >100 mg/day are associated with a higher risk of hospitalized allopurinol-associated severe cutaneous adverse reactions (AASCARs) (Ann Rheum Dis 2018).  We aimed to replicate these findings in a general population database from another country (Canada) and expand our investigation for an independent role of cardiovascular disease (CVD) on the risk of AASCARs.   

Methods: We used PopulationData BC, a population-based administrative database that covers the entire general population of British Columbia, Canada, to identify incident allopurinol users between 1999 and 2012. We examined the risk of hospitalized AASCARs according to purported key risk factors and used Poisson regression models to calculate relative risks (RR), adjusting for purported risk factors for AASCARs (Table).

Results: Among 451,897 allopurinol initiators, we documented 110 hospitalized AASCAR cases (mean age, 62 years; 71% male) during a mean follow-up of 3 months.  The risk of hospitalized AASCARs was apparent within 10 days of allopurinol initiation, peaked around one month after initiation, and declined progressively thereafter, reaching its nadir at the end of the third month (Figure).  Of the 110 cases, 10 (9%) died during hospitalization. The overall risk of hospitalized AASCARs was 1 out of 1185 allopurinol initiators (Table).  Female sex, older age (>60 years), CKD, and initial allopurinol dose (>100 mg/day) were independently associated with a 2.6-, 1.5-, 1.7-, and 2.8-fold higher risk of AASCARs, respectively (Table).  CVD was associated with a 2.5 higher risk of AASCARs after adjusting for other risk factors (RR, 2.45; 95% CI, 1.59 to 3.77), whereas diuretic use, a previously suspected risk factor, was not (RR, 1.05; 95% CI, 0.69 to 1.60) (Table).

Conclusion:  This general population-based cohort study confirms the independent role of older age, female sex, CKD, and initial allopurinol dose (>100 mg/day) in predicting a higher risk of AASCARs.  Furthermore, having CVD is also strongly associated with an increased risk of AASCARs, independent of these risk factors. These factors should be considered when initiating allopurinol to help prevent this extremely severe and potentially fatal adverse reaction.

 

 

Table 1. Risk of Hospitalized Allopurinol-Associated Severe Cutaneous Adverse Reactions According to Purported Risk Factors

 Risk Factor

Allopurinol Initiators, N (%)

Hospitalized SCARs,

N

Risk of Hospitalized

AASCARs

(/1000 persons)

Age-, Sex-Adjusted Relative Risk

Multivariable Relative Risk

All

130441 (100)

110

0.84 (0.69 to 1.02)

–

–

Sex

 

 

 

 

 

Male

93175 (71.4)

49

0.53 (0.39 to 0.70)

1.0

1.0

Female

37266 (28.6)

61

1.64 (1.25 to 2.10)

2.69 (1.84 to 3.95)

2.59 (1.75 to 3.84)

Age

 

 

 

 

 

<60 years

53898 (41.3)

23

0.43 (0.27 to 0.64)

1.0

1.0

≥60 years

76543 (58.7)

87

1.14 (0.91 to 1.40)

2.16 (1.35 to 3.44)

1.54 (0.94 to 2.54)

Chronic Kidney Disease

 

 

 

 

 

Yes

15885 (12.2)

27

1.70 (1.12 to 2.47)

1.87 (1.21 to 2.90)

1.72 (1.08 to 2.74)

No

114556 (87.8)

83

0.72 (0.58 to 0.90)

1.0

1.0

Hypertension

 

 

 

 

 

Yes

80095 (61.4)

85

1.06 (0.85 to 1.31)

1.52 (0.96 to 2.42)

1.23 (0.74 to 2.05)

No

50346 (38.6)

25

0.50 (0.32 to 0.73)

1.0

1.0

Cardiovascular Disease

 

 

 

 

 

Yes

31617 (24.2)

56

1.77 (1.34 to 2.30)

2.58 (1.74 to 3.83)

2.45 (1.59 to 3.77)

No

98824 (75.8)

54

0.55 (0.41 to 0.71)

1.0

1.0

Diabetes

 

 

 

 

 

Yes

32892 (25.2)

36

1.09 (0.77 to 1.52)

1.13 (0.75 to 1.69)

0.87 (0.57 to 1.33)

No

97549 (74.8)

74

0.76 (0.60 to 0.95)

1.0

1.0

Diuretic Use

 

 

 

 

 

Yes

42610 (32.7)

56

1.31 (0.99 to 1.71)

1.42 (0.95 to 2.11)

1.05 (0.69 to 1.60)

No

87831 (67.3)

54

0.61 (0.46 to 0.80)

1.0

1.0

Gout

 

 

 

 

 

Yes

79802 (61.2)

57

0.71 (0.54 to 0.93)

0.80 (0.54 to 1.17)

0.72 (0.49 to 1.06)

No

50369 (38.8)

53

1.05 (0.78 to 1.37)

1.0

1.0

Initial Allopurinol Dose (>100 mg/d)

 

 

 

 

 

Yes

82931 (63.6)

87

1.05 (0.84 to 1.29)

2.48 (1.56 to 3.93)

2.81 (1.76 to 4.48)

No

47510 (36.4)

23

0.48 (0.31 to 0.73)

1.0

1.0

 

 


Disclosure: N. Lu, None; C. Yokose, None; H. Xie, None; G. Li, None; S. K. Rai, None; S. C. Kim, None; H. K. Choi, Takeda, Selecta, Kowa, and Horizon, 5,Selecta and Horizon, 2.

To cite this abstract in AMA style:

Lu N, Yokose C, Xie H, Li G, Rai SK, Kim SC, Choi HK. Cardiovascular Disease, Other Purported Risk Factors, and Allopurinol-Associated Severe Cutaneous Adverse Reactions: A General Population-Based Cohort Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/cardiovascular-disease-other-purported-risk-factors-and-allopurinol-associated-severe-cutaneous-adverse-reactions-a-general-population-based-cohort-study/. Accessed .
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