Safety of non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating urate-lowering therapy for gout: an observational study in UK primary care using the Clinical Practice Research Datalink

Date of Approval: 
2020-09-25 00:00:00
Lay Summary: 
Gout causes sudden flares of severe joint pain and swelling. It affects 1 in 40 people, many of whom suffer recurrent flares. People get gout because the level of urate in their blood is too high. Long-term treatment for gout involves taking a tablet, usually allopurinol, to lower urate levels and prevent future flares. Although the long-term aim of treatment with allopurinol is to prevent future flares, when allopurinol is first started it can trigger a gout flare. To stop this from happening, guidelines recommend taking a second tablet, most commonly colchicine or a non-steroidal anti-inflammatory drug (NSAID), so that starting allopurinol does not trigger a flare. However, NSAIDs can cause significant side-effects such as bleeding from the stomach, and kidney and heart problems. This study will find out: - How common side-effects of NSAIDs are when people start taking allopurinol for gout. This research will benefit patients and the NHS by: - Enabling patients and doctors to make better informed treatment decisions. - Providing new evidence about the risk of side-effects of NSAIDs when people start allopurinol for gout. - Informing guidelines on safe and appropriate prescribing of NSAIDs.
Technical Summary: 
Gout affects 2.5% of adults in the UK and causes flares of severe joint pain and swelling. Long-term treatment for gout involves taking urate-lowering drugs (e.g. allopurinol) to prevent flares. However, allopurinol initiation commonly triggers a gout flare, hence co-prescription of prophylactic colchicine or NSAIDs to prevent flares is recommended. There is little evidence concerning the safety of NSAID prophylaxis when initiating allopurinol and we are currently conducting a similar study to this one to assess the risks associated with colchicine prophylaxis (protocol number 19_233). We will describe the safety of NSAID prescriptions when initiating allopurinol treatment for gout. The specific objective is to determine, in patients with gout commencing allopurinol, the risk of NSAID-related adverse events severe enough to warrant seeking healthcare. The study will be undertaken using linked primary care and Hospital Episode Statistics data. In a matched, retrospective cohort study, the incidence of NSAID-related adverse events (gastrointestinal, cardiovascular, and renal) will be compared using Cox proportional hazards regression between patients with gout initiating allopurinol who are prescribed and not prescribed NSAID prophylaxis. Matching will be based on propensity scores.
Health Outcomes to be Measured: 
Gastrointestinal, cardiovascular, and renal adverse events associated with NSAIDs that are serious enough to warrant seeking healthcare.
Application Number: 

Edward Roddy - Chief Investigator - Not from an Organisation
Sara Muller - Corresponding Applicant - Keele University
Christian Mallen - Collaborator - Keele University
Harry Forrester - Collaborator - Keele University
Lorna Clarson - Collaborator - Not from an Organisation
Ram Bajpai - Collaborator - Keele University
Rebecca Whittle - Collaborator - Keele University
Richard Partington - Collaborator - Keele University

HES Admitted Patient Care