Allopurinol, a medication prescribed for conditions such as gout, is associated with a number of severe skin-related side effects in some ethnic groups. These severe side effects, including Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis overlap syndrome (TEN), present as a rash alongside other symptoms and can have long-term health implications.
Currently, it is advised that special caution should be taken when prescribing allopurinol to particular ethnic groups (Han Chinese, Thai, Korean and those of Japanese or European origin). Genetic testing is not currently considered to determine the level of risk. An alternative, but more expensive medication, febuxostat, is prescribed when the risk of side effects to allopurinol is perceived as high.
It is known from previous research that severe skin-related reactions to allopurinol also occur more often in people of Black and Asian ethnic background associated with carrying a specific gene. However, the increased risk of these ethnicities is not currently acknowledged in the allopurinol product leaflet.
This study will quantify the prescribing of allopurinol and febuxostat to people of different ethnicities. The results of this study will help us to know the size of the population at risk of allopurinol side effects due that could benefit from a warning in the product information. The findings will be used to provide context to genetic study using Yellow card BioBank data to support a genetic link between ethnicity and increased risk of severe skin reactions due to allopurinol use with the goal to offer genetic testing to the at-risk population.
HLA-B*58:01 allele is more prevalent in some ethnic groups, making them susceptible to a number of severe adverse drug reactions (ADRs) from allopurinol, which is prescribed for gout and other conditions. These ADRs include Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis overlap syndrome (TEN). ADR reports received by the Medicines and Healthcare products Regulatory Agency (MHRA) in relation to allopurinol and these severe ADRs indicate an ongoing concern.
The allopurinol summary of product characteristics (SPC) provides a special warning about the potential increased risk of serious ADRs in specific sub-populations (Han Chinese, Thai, Korean) due to a higher prevalence of the HLA-B*58:01 allele carriage. However, people of other Asian and Black ethnicities are also more likely to carry the HLA-B*58:01 allele but are not mentioned in the SPC.
The study will estimate the population at risk of ADRs due to allopurinol. The population of interest will be those who were prescribed allopurinol or febuxostat (an alternative treatment) from 2016 to the present. A retrospective cross-sectional design will estimate the frequency of allopurinol and febuxostat prescribing in England among different ethnic groups. The study will use CRPD Aurum data combined with Hospital Episode Statistics Admitted Patient Care (HES APC). We will estimate the prevalence and annual incidence of allopurinol prescriptions in different ethnic groups since 2016, and quantify the ethnic sub-populations at risk of ADRs. This work will benefit patients in England and Wales by describing the population at-risk of ADRs due to allopurinol use for further research. The findings of this study will be used to support the design of a genetic study on the risk of severe ADRs due to the HLA-B*58:01 allele by Yellow Card BioBank, with a long-term aim of ensuring appropriate screening is offered prior to the commencement of treatment.
Frequency and distribution of allopurinol and febuxostat prescription between different ethnic groups.
Katherine Donegan - Chief Investigator - MHRA
Svetlana Buzdugan - Corresponding Applicant - MHRA
HES Admitted Patient Care