Dr Nigel Watson describes the action taken by his practice to ensure that all patients on DMARDs are adequately monitored, after audit revealed shortfalls


Azathioprine, methotrexate and sulphasalazine are often called disease-modifying antirheumatic drugs (DMARDs) and are indicated for the treatment of rheumatoid arthritis and other inflammatory arthropathies. Azathioprine and sulphasalazine are also used in the treatment of ulcerative colitis and Crohn's disease.

DMARDs are nearly always recommended and usually initiated by secondary care physicians, whereas the repeat prescribing of these drugs nearly always falls to GPs.

Adverse effects are not uncommon in patients taking DMARDs. Regular monitoring can reduce the risk of potentially serious side-effects and aims to detect reactions at an early stage.1

The following adverse reactions to DMARDs can be detected at an early stage2 with regular blood monitoring:

Haematological: Potentially fatal leucopenia, thrombocytopenia, agranulocytosis and aplastic anaemia
Liver: Hepatitis.

Azathioprine: Hepatotoxicity occurs in 3–10% of patients on azathioprine, reducing to 1% in those with rheumatoid arthritis.

Methotrexate: Has been shown in trials to cause an abnormality in liver function tests in up to 11% of patients.3 Adverse effects on the blood count have also been reported.

Sulphasalazine: About 75% of all adverse reactions to this drug occur in the first 3 months of treatment.4

It is well recognised that all patients taking DMARDs should have regular blood monitoring.5–6 Blood monitoring is ultimately the responsibility of the prescriber, i.e. the GP, but GPs usually expect this to be carried out in secondary care. A study in 1995 indicated that 70% of rheumatologists undertook monitoring through shared care with GPs.5


To establish a practice-based protocol for prescribing and monitoring DMARDs
To find out whether patients are being monitored adequately
To identify any problems with current monitoring
To take action to ensure that all patients taking DMARDs are adequately monitored.


A computer search was carried out to identify all patients registered with the practice who were currently being prescribed azathioprine, methotrexate or sulphasalazine.

Patient records, both manual and computer, were then examined for the results of any blood tests. Where results were not available, the hospital was contacted to obtain the latest blood test results.


Full blood count (FBC)

Azathioprine,7 methotrexate8 and sulphasalazine9 can cause bone marrow suppression or isolated thrombocytopenia or leucopenia. The recommended frequency of monitoring of FBC is shown in Table 1, below.

Liver function tests (LFTs)

Cholestasis and deterioration of liver function has been reported in patients taking azathioprine,5 methotrexate6 or sulphasalazine5.

The recommended frequency of monitoring of LFTs is shown in Table 1.

Table 1: Recommended frequency of monitoring full blood count and liver function tests in patients taking a DMARD
  Azathioprine Methotrexate Sulphasalazine
Full blood count 3-monthly monthly 3-monthly
Liver function tests 3-monthly monthly 3-monthly


Standards in patients taking a DMARD are as follows:

FBC in past 3 months 100%
LFTs in past 3 months 100%
FBC in past month 100%
LFTs in past month 100%
FBC in past 3 months 100%
LFTs in past 3 months 100%


The practice has 12 400 registered patients. A computer search identified a total of 63 patients currently being prescribed DMARDs: azathioprine (17), methotrexate (24), and sulphasalazine (22).

The indications for the prescription of a DMARD in the 63 patients are shown in Table 2, below.

The results of monitoring patients on DMARDs are shown in Figure 1, below.

Table 2: Reason for being prescribed a DMARD

  No. of patients being prescribed a DMARD
Rheumatoid arthritis
Ulcerative colitis
Crohn's disease
Renal transplant
Polymyalgia rheumatica


Figure 1: Results of DMARDs blood monitoring








FBCs in practice patient records
5 (29%)
4 (17%)
9 (41%)
FBCs in practice and hospital records
12 (71%)
15 (62.5%)
9 (41%)
LFTs in practice patient records
8 (47%)
4 (17%)
8 (36%)
LFTs in practice and hospital records
12 (71%)
15 (62.5%)

8 (36%)

bar chart showing results of dmards blood monitoring


DMARDs are both powerful and effective treatments for a number of clinical conditions. Regular blood monitoring can significantly reduce the incidence of adverse events.

Patients of the practice attend two local hospitals. In one hospital, monitoring is performed on an ad hoc basis when the patient is seen in the outpatient department. In the other hospital, the rheumatology department has a well developed nurse-led monitoring service.

The results suggest that there is a failure to monitor these treatments adequately. The following problems have been identified:

The patient is failing to have the blood test at the correct time
The hospital is performing the test, but the results are not being forwarded to the practice.

The group of patients who are regularly monitored by the hospital and whose blood results are not regularly copied to the practice were identified. The pathology laboratory and hospital department were contacted to find the results.

Of the 63 patients taking DMARDs, 17 (27%) were taking them for non-rheumatological conditions.

It would appear that the hospital with the nurse-led service monitors the patients at regular intervals but rarely sends the blood results to the practice.

The patients who are receiving DMARDs for non-rheumatological conditions do not have access to a nurse-led, hospital-based blood monitoring service.

Most guidelines have similar recommendations for the monitoring of azathioprine and methotrexate, in terms of which blood tests to perform and frequency of testing.

Advice on monitoring of sulpha-salazine shows much wider variation. The datasheet for sulphasalazine2 recommends monitoring of FBC and LFTs every 3 months, whereas the BNF10 recommends FBC and LFTs for the first 3 months only.

The current situation is unacceptable and is providing a poor quality service to this group of patients.


When patients are first prescribed a DMARD, they are informed of the potentially serious side-effects and need for regular blood monitoring.
A list of the patients on DMARDs has been circulated to all partners.
Patient information leaflets, giving clear instructions on monitoring, have been produced for each DMARD.
The results of the audit have been with the local hospitals.
A responsible GP has been identified for each patient.
Steps have been taken to ensure that all blood tests performed by the hospital are copied to the practice.
We have clarified with the hospital department who will carry out the regular monitoring.
A call and recall system has been set up in the practice for patients who fail to attend for blood monitoring.
The widespread introduction of shared care cards, or patient-held record cards is being considered.


These results are likely to be reflected in most practices. As part of the Health Improvement Plan and Primary Care Development Plan, monitoring of patients on DMARDs needs to be addressed.

The quality of the blood monitoring needs to be improved and additional resources identified.

As the prescribing of these drugs is performed mainly by GPs, the monitoring becomes the responsibility of the GP. The responsibility and additional resources need to be explicit in each practice. The responsibility should only be devolved to secondary care when the practice is certain that adequate blood monitoring is carried out.

In 1997, Nottingham Local Medical Committee negotiated with the health authority for the monitoring of patients on DMARDs in primary care. The agreement reached was a payment to the practice of £80 per patient per year, during the first year, decreasing to £60 per patient per year in the second and subsequent year, subject to the practice signing an agreement to reach agreed standards of care.


Blood monitoring of patients on DMARDs should be performed in a structured way. The quality of this monitoring should form part of PCGs' clinical governance agenda. Agreement should be reached with the hospital practice and PCG as to how the blood monitoring is carried out.


  1. Wijnands MJH, van Reil PLCM. Management of adverse effects of disease modifying antirheumatic drugs. Drug Safety 1995; 219-27.
  2. MeReC Bulletin 1996; 7: 9-12.
  3. Methotrexate. Clinical Evidence, December 1999, issue 2: 450-1.
  4. Datasheet Compendium 1999–2000: Sulphasalazine, p. 1234.
  5. Cromer M, Scott D, Doyle D, Huskisson E, Hopkins A. Are slow-acting anti-rheumatic drugs monitored too often? Br J Rheumatol 1995; 34: 966-70.
  6. BNF 38, September 1999: 451-2.
  7. BNF 38, September 1999: 388.
  8. BNF 38, September 1999: 507.
  9. Hopkinson ND, Saiz Garcia F, Gumpel JM, Haematological side-effects of sulphasalazine in inflammatory arthritis. Br J Rheumatol 1989; 28: 414-17.
  10. BNF 38, September 1999: 45.

Guidelines in Practice, June 2000, Volume 3
© 2000 MGP Ltd
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