Sulfasalazine Induced Neutropaenia

Sulfasalazine Induced Neutropaenia (SAN) in IBD and Rheumatoid Arthritis was added to the Predicting Drug Side Effects in Gastroenterology (PRED4) at the beginning of 2014.

The inclusion criteria are as follows:

  • History of inflammatory bowel disease or Rheumatoid Arthritis
  • History of sulfasalazine exposure in the previous 30 days
  • Normal total white cell count and neutrophil count at baseline
  • Fall in neutrophil count to ≤0.5×109/L
  • Medical opinion implicating sulfasalazine leads to dose reduction or drug withdrawal (even if temporary)


Codes which we have found helpful to identify patients:

 * Ask Haematology to search for patients who have been referred by the Gastro or Rheumatology teams with total neutrophil count ≤0.5×109/L

* Talk to your Rheumatologists

* Combine for Ulcerative Colitis (K51) + Y40-Y59 (Drugs, medicaments and biological substances causing adverse effects in therapeutic use)

Or Combine for Crohn’s Disease (K50) + Y40-Y59 (Drugs, medicaments and biological substances causing adverse effects in therapeutic use)

*For a more specific search cross reference against Ulcerative Colitis (K51) and Crohn’s Disease (K50):

Analgesics, Antipyretics and Anti-inflammatory drugs (Y45)

* Combine for Ulcerative Colitis (K51) + D70 (D70.2) (Agranulocytosis, which includes drug-induced neutropaenia)

Or Combine for Crohn’s Disease (K50) + D70 (D70.2) (Agranulocytosis, which includes drug-induced neutropaenia)


Strategies for searching patients

It is proving very challenging for all the sites to recruit patients to the Sulfasalazine induced agranulocytosis arm of the study. The use of this drug has dwindled over the years especially in IBD. It is now more often used in Rheumatology. Therefore, most of the agranulocytosis events would be many years old and thus difficult to search for. At Royal Devon and Exeter Hospital, we tried various strategies to search from various hospital databases. The most productive ones are detailed in steps below:

Strategy 1:

  1. With help from your IT department, search through document management software (program that stores the clinic letters, discharge summaries and other clinical documents) for the following terms:
    1. Sulfasalazine AND neutropaenia
    2. Sulfasalazine AND agranulocytosis
    3. Sulfasalazine AND low white cell count
  2. This will give you a list of patients where a document contains both the search terms. Individually reviewing these particular documents will allow you elucidate and select patients which had sulfasalazine induced neutropaenia
  3. A review of the notes and/or the pathology database (blood tests) would let you determine which of these patients are likely to meet inclusion criteria. These patients can then be contacted regarding taking part in the study

Strategy 2:

  1. With the help of your lab, search Pathology database for all blood tests with White cell count <0.5. As this is likely to produce a very large number of results, we recommend searching for 1-2 years at a time.
  2. With the help of IT department, do a separate search in document management software for the term ’Sulfasalazine’
  3. Compare the patient numbers obtained in the two lists in excel to find patients that were referred to in both the lists i.e. had WCC <0.5 and had a document with the word sulfasalazine.
  4. Review blood tests/clinic letters/case notes for these patients to determine patients that can be included in the study


In Exeter, we could find 8 patients that qualified for the trial using these methods in a short period of time. We can meet our target if each site gets only a few patients.

Kindly see which strategy is better suited to your hospital and try to apply it to find the patients for this arm of the study. If you need to have any of these strategies explain to you please con tact the team.



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