THU0184 PREVIOUSLY UNKNOWN GASTRO-INTESTINAL ADVERSE DRUG REACTIONS ATTRIBUTED TO ETANERCEPT
Authors: J. Van Lint, N. Jessurun, A. Van Tubergen, M. Van Doorn, E. Van Puijenbroek, P. Spuls, S. Tas, B. Van den Bemt, M. Nurmohamed, F. Hoentjen, H. Vonkeman
Journal: Annals of the Rheumatic Diseases (2020)

Background: Although an increased risk of inflammatory bowel disease (IBD) during etanercept (ETN) use is included in the product information of ETN, no other gastro-intestinal (GI-)adverse drug reactions (ADRs) are described. This is in contrast with other TNFα-inhibitors such as adalimumab (ADA) and infliximab, as these are associated with various GI-ADRs such as nausea and abdominal pain. Objectives: To identify the proportion and type of patient-reported and health care professional (HCP)-reported ETN associated GI-ADRs and compare these with ADA associated GI-ADRs. Methods: Patient-reported data on ADRs attributed to biologics was collected from the Dutch Biologic Monitor (DBM) from 1 Jan 2017 until 1 Nov 2019. HCP reported data on ADRs attributed to biologics was collected from the Dutch rheumatic arthritis monitoring registry and the Dutch registry for spondyloarthritis from 22 Jun 2004 until 1 Nov 2019. GI-ADRs were defined by MedDRA System Organ Class ‘Gastrointestinal disorders’. All reported GI-ADRs attributed to ETN and ADA for patients with inflammatory rheumatic diseases (IRDs) were selected. Proportion of GI-ADRs for ETN and ADA in patient and HCP reports was defined as the number of patients with at least one GI-ADR per total number of patients using ETN or ADA. Patient-reported burden and actions taken after GI-ADRs were compared between ETN and ADA. Results: We included 755 patients from the DBM using ETN (415) and ADA (358) for IRDs, of which 47 patients reported 60 GI-ADRs. The proportion of patient-reported GI-ADRs was 6.3% for ETN and 5.9% for ADA (Table 1). We included 1343 patients using ETN (804) or ADA (796) from the registries, with 43 HCP-reported GI-ADRs in 38 patients. The proportion of HCP-reported GI-ADRs was 1.6% for ETN, which was significantly lower than 3.4% for ADA (p=0.049). Patients experienced ETN associated GI-ADRs more burdensome than ADA associated GI-ADRs (p=0.05 using Mann-Whitney U) (Table 2). The ADR required action in 34% of patient-reported GI-ADRs attributed to ETN and 41% of GI-ADRs attributed to ADA, including biologic discontinuation. No hospitalisation following a GI-ADR was reported. Table 1. Proportion of patient- and HCP-reported GI-ADRs attributed to ETN and ADA. Patients Proportion for ETN Top 3 Proportion for ADA Top 3 p-value* DBM (n=755; 415 ETN, 358 ADA) 6.3% (26 pt) 1. Nausea: 6 2. Diarrhea: 5 3. Abdominal pain: 5 5.9% (21 pt) 1. Nausea: 8 2. diarrhea: 3 3. Oral aphthous ulcer: 2 0.9 Registries (n=1,343; 804 ETN, 796 ADA) 1.6% (13 pt) 1. diarrhoea: 6 2. Nausea: 2 3. Abdominal pain: 2 3.4% (25 pt) 1. Nausea: 7 2. Abdominal pain: 6 3. Diarrhoea: 5 0.049 *Differences between ETN and ADA were tested using Fisher’s exact Table 2. Actions following patient-reported GI-ADRs attributed to ETN and ADA in the DBM ETN (n=38) ADA (n=22) Mean burden score* ± SD 2.9 ± 1.0 2.5 ± 0.9 Contact HCP 23 (61%) 10 (45%) Specialist doctor 10 (43%) 3 (30%) General practitioner 10 (43%) 8 (80%) Nurse 6 (26%) 2 (20%) Other 7 (30%) 2 (20%) Action of HCP Discontinuation 1 (4%) 1 (10%) Dose adjustment 2 (9%) 1 (10%) Treatment 4 (17%) 3 (30%) Referral 3 (13%) 2 (20%) Mentioned, no action 12 (52%) 5 (50%) Other 3 (13%) 2 (20%) *5 point Likert scale Conclusion: Although GI-ADRs other than IBD are not included in the product information of ETN, they are often reported by both patients and HCPs. The type of patient-reported GI-ADRs attributed to ETN and ADA is comparable. However, patients regard GI-ADRs attributed to ETN as more burdensome. Disclosure of Interests: Jette van Lint: None declared, Naomi Jessurun: None declared, Astrid van Tubergen Consultant of: Novartis, Martijn van Doorn Grant/research support from: Unrestricted grants, advisory board, speaker fees and/or other (investigator) from Novartis, Abbvie, Janssen Cilag, Leopharma and Pfizer, Speakers bureau: Unrestricted grants, advisory board, speaker fees and/or other (investigator) from Novartis, Abbvie, Janssen Cilag, Leopharma and Pfizer, Eugène van Puijenbroek: None declared, Phyllis Spuls Grant/research support from: Departmental independent research grant for TREAT NL registry LeoPharma December 2019; Contract support: I am involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis for which we get financial compensation paid to the department/hospital, Consultant of: Consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid), Sander Tas: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer and Abbvie, Consultant of: Delivered consultancy work for UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen and Sandoz., Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research, Frank Hoentjen Grant/research support from: Received grants from Dr Falk, Janssen-Cilag, and AbbVie., Consultant of: Served on advisory boards, or as speaker or consultant for AbbVie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz, and Dr Falk, Speakers bureau: Served on advisory boards, or as speaker or consultant for AbbVie, Celgene, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz, and Dr Falk, Harald Vonkeman: None declared