Background

According to recent British Society of Gastroenterology (BSG) guidelines, oral 5-ASA (5-aminosalicylic acid drugs, such as mesalazine and sulfasalazine) is standard therapy for mild to moderately active ulcerative colitis, and the guidelines recommend treatment with both oral and enema 5-ASA. Treatment with 5-ASA for Crohn's disease has also been common in the past, although is no longer recommended for remission or maintenance treatment.

However, 5-ASA may be associated with renal complications and in particular, patients can rarely develop an idiosyncratic tubulointerstitial nephritis. This can cause significant renal impairment, with the risk associated with 5-ASA use being estimated at 1 in 4,000 patients per year (Muller article).

A retrospective study published in 2016 (Heap et al) reviewed data from 151 patients with inflammatory bowel disease and definite or probable 5-ASA associated nephrotoxicity. 30% of patients recovered renal function completely upon drug cessation, with the likelihood of renal recovery inversely related to the duration of 5-ASA treatment and average drug dose. Nearly 10% of patients required renal replacement therapy.

The study found that chronic renal damage associated with 5-ASA is more common in males, and can occur after many years of drug treatment. Therefore, whilst this complication is rare, the effects for an individual patient can be devastating.

Studies have shown that many patients do not have regular monitoring of renal function whilst taking 5-ASA (from Heap et al 2016). In 1990, the UK Committee on the Safety of Medicines issued an alert on nephrotoxic reactions to mesalazine, and in 2001, the Drug and Therapeutics bulletin suggested that annual checking of renal function in patients taking 5-ASA was of unproven value but 'seems prudent'.

The BNF didn't contain advice about monitoring renal function in patients taking 5-ASA until 2004, and that advice only referred to elderly patients. Recommendations regarding monitoring of renal function on 5-ASA drugs have changed over the years, and also haven't necessarily been consistent across different sources of guidance. In addition, these publications also probably don't reflect the knowledge of the majority of GPs in particular regarding the potential need to monitor renal function.

The latest BSG guidelines on management of inflammatory bowel disease in adults make a strong recommendation that renal function is checked before treatment with 5-ASA, after two to three months of treatment, and annually thereafter - with more close monitoring if renal function is impaired.

The current BNF recommends that renal function should be monitored before starting an oral aminosalicylate, at three months of treatment, and then annually during treatment, with more frequent monitoring in patients with renal impairment.

Issues identified from MDU cases

The claims notified to the MDU tend to concern patients who either require renal replacement therapy or those with very significant renal impairment who may well reach end stage renal disease in the future. Therefore in those claims that have been settled, compensation payments have been in the region of £500,000.

Some of the issues common to those cases seen by the MDU include:

1. failure by secondary care doctors recommending treatment with 5-ASA drugs to advise the GPs about recommendations to monitor renal functions
2. failure by both primary and secondary care to check renal function before starting treatment with 5-ASA drugs
3. failure by both primary and secondary care to monitor renal function during 5-ASA treatment
4. a lack of regular medication reviews by general practitioners in patients receiving long term treatment with 5-ASA drugs
5. a failure to act on abnormal renal function resulting in a delay in diagnosis of 5-ASA associated renal impairment in both primary and secondary care.

Recommendations

It is extremely common for GPs to issue continuing prescriptions of medication to patients following recommendations from secondary care. Generally speaking, 5-ASA treatment for inflammatory bowel disease would be initiated by gastroenterologists or surgeons, with ongoing prescriptions then being issued by the patient's own GP.

In the MDU's experience, this is generally without a formal shared care agreement. However, GPs may only have a handful of patients with inflammatory bowel disease registered at their practice, and may not be that familiar with 5-ASA drugs and in particular their monitoring requirements.

In the cases the MDU has seen, advice to monitor renal function has not been provided to the GPs by the gastroenterologist or surgeon recommending the treatment - perhaps because the risk of 5-ASA associated nephrotoxicity is low.

GMC guidance

The GMC's Prescribing and managing medicines and devices states that GPs are responsible for the prescriptions they sign. The guidance recommends that if you prescribe at the recommendation of another doctor, nurse or other healthcare professional, you must satisfy yourself that the prescription is needed, appropriate for the patient and within the limits of your competence.

It goes on to say that if you recommend that a colleague - for example, a junior doctor or general practitioner - prescribes a particular medicine for a patient, you must consider their competence to do so. You must satisfy yourself that they have sufficient knowledge of the patient and the medicine, experience (especially in the case of junior doctors) and information to prescribe.

Dr Claire Wratten

Dr Claire Wratten

Dr Claire Wratten is a senior medical claims handler and claims team manager, who joined the MDU in 2006 from a background in nephrology and general medicine.

See more by Dr Claire Wratten