A recent study, published in Drug Safety, aimed to describe the adverse drug reactions reported in inflammatory bowel disease patients from real-world data, using the Dutch nationwide IBDREAM registry. In addition to that, the researchers worked to compare the occurrence and cumulative incidences of these reactions with the Summary of Product Characteristics of the associated drugs.
Inflammatory bowel disease (IBD)
IBD encompasses ulcerative colitis (UC), Crohn’s disease (CD) and IBD unclassified (IBD-U). These conditions are characterised by a chronic relapsing and remitting inflammation of the digestive tract. At present, immunosuppressants and biologicals are used for treatment and to maintain a state of remission in IBD. Treatment selection is based on a number of factors, including location, disease severity, previous treatment response, possible adverse drug reactions (ADRs) and patient preference.
Current drug safety profiles may not reflect the complete spectrum of ADRs outlined in the Summary of Product Characteristics (SmPC). The SmPC is a summary of the data derived from clinical trials, post-authorisation safety studies and spontaneous reports. In theory, the information included in this summary should match the ADRs seen in daily practice. However, as the ADRs in the SmPC are based on reactions seen in the controlled circumstances of trials, the SmPC may not give an accurate overview of the type and incidence of ADRs that may occur in the daily clinical setting. Therefore, it may be difficult to choose the most favourable drug for each patient considering individual factors, such as comedication.
Real-world data and adverse drug reactions in IBD
Nationwide registries that collect real-world data about ADRs can be used to enlarge the SmPC information. In summary, the IBDREAM registry is a multicentre registry that was developed for IBD patients in the Netherlands. Any ADRs that are reported and registered as part of IBDREAM are directly forwarded to the Netherlands Pharmacovigilance Centre. Real-world ADR incidences can provide better understanding of the possible risks of certain treatments and could therefore lead to improved clinical care for IBD patients.
Therefore, the aim of this study was to use the IBDREAM registry to describe the frequency of ADRs, reported by healthcare professionals, in IBD patients from real-world data and compare them with the SmPCs for the associated therapies. The researchers also hoped to be able to describe new drug-ADR associations that were not reported in the current SmPCs, and incidences of ADRs that were different in the SmPCs.
Using the IBDREAM registry to assess ADRs in IBD patients
The researchers carried out this retrospective multicentre cohort study including all patients that had a clinical diagnosis of CD, UC or IBD-U according to the international guidelines. More specifically, they assessed all ADR reports relating to IBD medication originating from the IBDREAM registry, which includes patients from 5 different hospitals. ADRs were included if they were associated with the use of drugs indicated for the maintenance treatment of IBD.
The assessed drugs include:
- Mesalamine– assessed separately for oral and rectal administration.
- Methotrexate – assessed separately for oral and subcutaneous administration.
The cumulative incidences of the ADRs were calculated and compared with the associated SmPCs.
All the reported ADRs were codded by pharmacovigilance assessors according to the Medical Dictionary for Regulatory Activities (MedDRA) codes. In summary, MedDRA contains five hierarchical grouping levels, ranging from general to specific descriptions. The most specific level is the ‘Lowest Level Term’ (LLT), which is linked to one ‘Preferred Term’ (PT). PTs are grouped into ‘High Level Terms’ (HLTs) based on anatomy, aetiology and function. HLTs are consecutively linked to ‘High Level Group Terms’ (HLGTs) and finally grouped into ‘System Organ Classes’ (SOCs) based on aetiology, manifestation site or purpose. This study used PTs to describe ADRs.
When comparing ADRs to the SmPC the frequency categories used were ‘very common’ (≥ 10%), ‘common’ (≥ 1% to < 10%), ‘uncommon’ (≥ 0.1% to < 1%), ‘rare’ (≥ 0.01% to < 0.1%), ‘very rare’ (< 0.01%) or unknown.
Results using the IBDREAM registry to assess ADRs
Overall, 3,080 ADRs were reported in 1,179 patients in the IBDREAM registry. A total of twenty-three new drug-ADR associations related to the use of azathioprine, mercaptopurine, infliximab, oral mesalamine and thioguanine were reported in the IBDREAM registry, which were not mentioned in the corresponding SmPCs. Moreover, the most frequently reported new-drug ADR association was pyrexia for azathioprine (3.1%) and mercaptopurine (4.9%). In addition to that, there were seven ADRs with a higher overall incidence in IBDREAM compared with SmPC. These ADRs included arthralgia during mercaptopurine use (2.5%), and diarrhoea (1.4%), alopecia (1.2%) and infections (1.6%) during azathioprine use.
This study used the IBDREAM registry to assess real-world data for ADRs reported as a result of treatment for IBD. The researchers compared the real-world data with the information reported in the SmPC and found a higher incidence of ADRs in the real-world setting as well as cases of new
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