Off-label Prescriptions of Drugs Used for the Treatment of Crohn's Disease or Ulcerative Colitis

Melek Simsek; Birgit I. Lissenberg-Witte; Milou L. M. van Riswijk; Sander Verschuren; Frank Hoentjen; Bas Oldenburg; Cyriel Y. Ponsioen; C. Janneke van der Woude; Andrea E. van der Meulen; Marieke Pierik; Gerard Dijkstra; Nanne K. H. de Boer; On behalf of the Parelsnoer Institute (PSI); the Dutch Initiative on Crohn's and Colitis (ICC)


Aliment Pharmacol Ther. 2019;49(10):1293-1300. 

In This Article

Abstract and Introduction


Background: Off-label prescribing is encountered across various fields of medicine and creates alternative treatment options, but is associated with unknown safety risks. The use of off-label drugs for the treatment of patients with inflammatory bowel diseases (IBD) has not been characterised before.

Aim: To assess the proportion and characteristics of off-label prescribing for IBD in tertiary care centres in the Netherlands.

Methods: A prospective database of IBD patients from all Dutch university hospitals was used to collect data on drug prescriptions for IBD and demographics. Drugs were classified as off-label if they were unlicensed for Crohn's disease and/or ulcerative colitis by the Medicines Evaluation Board. Uni- and multivariable analyses were used to identify patient-specific characteristics predictive of increased off-label use.

Results: For the induction and/or maintenance treatment of 4583 IBD patients, 12 651 historical and current drug records were available in the database. Of these, 2374 (19%) were considered off-label prescriptions. Out of 4583 IBD patients, 1477 (32%) were exposed to off-label drugs. Commonly prescribed off-label IBD drugs were mercaptopurine (18%), beclomethasone (12%), thioguanine (4%) and allopurinol (3%). Non-thiopurine/methotrexate off-label drugs were prescribed in 243 patients (6%), including biological agents or tofacitinib in 47 IBD patients (1%). Off-label prescriptions were more common in ulcerative colitis than Crohn's disease (37% vs 29%, P < 0.001). Smokers and patients that received ≥5 drug types during their disease course were more likely to be exposed to off-label drugs (smoking 33% vs 27% and multiple drug use 66% vs 22%, both P < 0.001).

Conclusion: About one-fifth of prescriptions for IBD were off-label and one-third of IBD patients, especially ulcerative colitis patients, were exposed to off-label drugs.


Off-label drug prescribing is widespread in daily clinical practice and includes the use of drugs outside the licensed indication, dosage, route of administration or age.[1] Examples of widely prescribed off-label drugs include the use of beta-blockers for anxiety, tricyclic antidepressants for chronic pain and oral contraception to treat endometriosis or acne.

Off-label drugs may create alternative therapeutic options, but have also been associated with safety risks since they are under-evaluated for unlicensed indications.[2] A lack of drug approval by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) generally means a shortage of scientific scrutiny as compared to labelled indications.[3] In a large Canadian cohort, the rate of preventable adverse drug reactions was considerably higher in off-label prescriptions (19.7 per 10 000 person-months) as compared to on-label prescriptions (12.5 per 10 000 person-months).[2]

Although off-label prescribing is legal and common in most countries, physicians carry primary responsibility for accurately prescribing and monitoring therapy with off-label drugs, as acknowledged by the Medicines Healthcare product Regulatory Agency (MHRA) and the General Medical Council (GMC) in the United Kingdom (UK).[4,5] Several studies reported on the inadequate awareness of off-label drugs by physicians and patients. In a survey among 600 physicians in the US, 45% was unaware of the FDA status of the medications they prescribed.[6] In a teaching hospital in India, two-thirds of the residents had insufficient knowledge on unlicensed drugs, and one-third assumed that off-label prescribing was not legal.[7]

The use of off-label drugs seems to vary between different fields of medicine. In the intensive care unit and paediatrics, off-label prescription rates were up to 36% and 62%, respectively.[8,9] In oncology, off-label drug prescriptions were in the range of 18%-41% for hospitalised cancer patients and 7%-50% for ambulatory care patients.[10] In the largest cohort study among office-based physicians, an estimated 21% of overall prescriptions (725 million) were off-label.[11]

In the treatment of inflammatory bowel diseases (IBD), off-label drugs are prescribed as well, especially in patients who failed standard treatment regimens. The overall magnitude of off-label prescribing for Crohn's disease and ulcerative colitis is unknown. To provide optimal therapeutic care, a better understanding of off-label drug prescriptions in this field is needed. We aimed to assess the proportion and characteristics of off-label prescribing for IBD.