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 called colchicine so that starting allopurinol does not trigger a flare. However, colchicine can cause significant side-effects such as diarrhoea and problems with nerves and muscles. These side-effects are thought to be more common in people with kidney disease and people taking certain tablets, such as statins. However, it is not known how often these side-effects occur or whether the risk of them is genuinely increased by other medical problems or other tablets.
This study will find out:
- How common side-effects of colchicine are when people start taking allopurinol for gout?
- Which factors are linked to risk of these side-effects?
- Which patient groups experience these side-effects
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 colchicine when people start allopurinol for gout.
- Helping doctors to work out who is at higher risk of side-effects from taking colchicine.
- Informing guidelines on safe and appropriate prescribing of colchicine.
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 to prevent flares is recommended. There is little evidence concerning the safety of colchicine prophylaxis despite colchicine being known to interact with several commonly prescribed drugs.
We will describe the safety of colchicine prophylaxis when initiating allopurinol treatment for gout, and assess prognostic factors for colchicine side-effects.
Specific objectives are to determine, in patients with gout prescribed colchicine prophylaxis when initiating allopurinol:
1. Risk of colchicine-related adverse events severe enough to warrant seeking healthcare;
2. Incidence of co-prescribing of drugs with the potential to interact with colchicine;
3. Prognostic factors for adverse events.
The study will be undertaken using linked primary care and Hospital Episode Statistics data.
Work-package 1
Matched, retrospective cohort study. The incidence of colchicine-related adverse events (diarrhoea, nausea, vomiting, neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression) will be compared using Cox proportional hazards regression between patients with gout initiating allopurinol with and without colchicine. Matching will be based on propensity scores.
Work-package 2
Using the exposed group from the work-package 1, we will describe the proportion of people with gout initiating allopurinol with colchicine prophylaxis who have a current prescription for medications (statins, fibrates, verapamil, diltiazem, digoxin, amiodarone, oral ketoconazole, macrolide antibiotics) that could potentially interact with colchicine.
Work-package 3
Type II prognosis study. In the same exposed group, we will assess potential prognostic factors (age, gender, body mass index, chronic kidney disease, multimorbidity and co-prescriptions) for adverse events. Absolute risk of adverse events by potential prognostic factors will be quantified and Cox regression used to examine potential risk factors for adverse events.
Work packages 1 and 3.
Adverse events associated with colchicine that are serious enough to warrant seeking healthcare: diarrhoea; nausea; vomiting; neuropathy; myalgia; myopathy; rhabdomyolysis; bone marrow suppression.
Work package 2
Prescription of drugs that have the potential to interact with colchicine: statins; fibrates; verapamil; diltiazem; digoxin; amiodarone; oral ketoconazole; macrolide antibiotics.
Edward Roddy - Chief Investigator - Keele University
Ram Bajpai - Corresponding Applicant - Keele University
Christian Mallen - Collaborator - Keele University
Harry Forrester - Collaborator - Keele University
Lorna Clarson - Collaborator - Keele University
Rebecca Whittle - Collaborator - Keele University
Richard Partington - Collaborator - Keele University
Sara Muller - Collaborator - Keele University
HES Admitted Patient Care