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Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study
  1. Sarah F Keller1,
  2. Na Lu1,
  3. Kimberly G Blumenthal1,
  4. Sharan K Rai1,
  5. Chio Yokose1,
  6. Jee Woong J Choi1,
  7. Seoyoung C Kim2,3,
  8. Yuqing Zhang1,
  9. Hyon K Choi1
  1. 1Division of Rheumatology, Allergy and Immunology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2Division of Pharmacoepidemiology and Pharmacoeconomics, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  3. 3Division of Rheumatology, Immunology and Allergy, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Hyon K Choi, Division of Rheumatology, Allergy, and Immunology Department of Medicine, Massachusetts General Hospital, Boston MA 02114, USA; hchoi{at}partners.org

Abstract

Objectives To examine associations of race/ethnicity and purported risk factors with hospitalised allopurinol-associated severe cutaneous adverse reactions (AASCARs).

Methods We used US Medicaid data to identify incident allopurinol users between 1999 and 2012. We examined the risk of hospitalised AASCARs according to race/ethnicity and purported key risk factors and calculated relative risks (RR).

Results Among 400 401 allopurinol initiators, we documented 203 hospitalised AASCAR cases (1 in 1972 initiators). The average AASCAR hospitalisation was 9.6 days and 43 individuals (21%) died. The multivariable-adjusted RRs for AASCARs among blacks, Asians and Native Hawaiians/Pacific Islanders compared with whites or Hispanics were 3.00 (95% CI 2.18 to 4.14), 3.03 (95% CI 1.72 to 5.34) and 6.68 (95% CI 4.37 to 10.22), respectively. Female sex, older age (≥60 years), chronic kidney disease and initial allopurinol dose (>100 mg/day) were independently associated with a 2.5-fold, 1.7-fold, 2.3-fold and 1.9-fold higher risk of AASCAR, respectively. In our combined demographic analysis, older women (≥60 years) of a high-risk race/ethnicity (blacks, Asians or Native Hawaiians/Pacific Islanders) had over a 12-fold higher risk of hospitalised AASCARs than younger men of a low-risk race/ethnicity (whites or Hispanics) (multivariable-adjusted RR, 12.25; 95% CI 6.46 to 23.25).

Conclusions This racially diverse (yet mostly white) cohort study indicates that the risk of hospitalised AASCAR is rare overall, although blacks, Asians and Native Hawaiians/Pacific-Islanders have a substantially higher risk of hospitalised AASCARs, particularly among older women. These data also support the practice of initiating allopurinol at a low dose (eg, ≤100 mg/day).

  • gout
  • epidemiology
  • health services research

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Footnotes

  • SFK and NL contributed equally.

  • Handling editor Josef S Smolen

  • Contributors All authors participated in the conception, design and analyses of the study. SFK, NL and HKC drafted the manuscript and are guarantors. All authors contributed to interpretation of the results. SFK, NL and HKC had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding This work was supported in part by a grant from the National Institutes of Health (R01AR065944).

  • Competing interests HKC has received research grants from Pfizer and Astra-Zeneca to Massachusetts General Hospital for unrelated studies and served as a consultant for Takeda Pharmaceuticals, Selecta, Horizon and Ironwood. SCK has received research grants to the Brigham and Women’s Hospital from Pfizer, AstraZeneca, Bristol-Myers Squibb and Roche for unrelated studies.

  • Patient consent Not required.

  • Ethics approval This study was exempted by the Partners Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional unpublished data are available.

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