OP0208 PATIENTS REPORT FATIGUE AS AN ADVERSE DRUG REACTION OF BIOLOGICS
Authors: J. Van Lint, T. Bakker, J. Ubbink, M. Van Doorn, P. Spuls, S. Tas, H. Vonkeman, F. Hoentjen, B. Van den Bemt, M. Nurmohamed, E. Van Puijenbroek, N. Jessurun
Journal: Annals of the Rheumatic Diseases (2020)

Background: Chronic fatigue is a well-known symptom in patients with rheumatic diseases and other immune-mediated inflammatory diseases (IMIDs). Therefore, fatigue as an adverse drug reaction (ADR) to biologics may remain unrecognised or may erroneously be attributed to the disease. Objectives: To assess patient-reported fatigue attributed to biologics for IMIDs and investigate predisposing factors of patient-reported fatigue. Methods: The Dutch Biologic Monitor is a multicenter patient-reported ADR monitoring system that surveys patients using a biologic for an IMID. Patients completed web-based questionnaires regarding ADRs attributed to biologics and the course and experienced burden (5 point Likert scale) of these ADRs. All patient-reported ADRs with MedDRA Preferred Term ‘fatigue’ were defined as biologic-associated fatigue (BA-fatigue). Basic demographics and treatment characteristics were compared between patients reporting BA-fatigue and patients not reporting BA-fatigue (reported other ADRs or no ADRs). Results: Out of 1369 participating IMID patients, 696 patients reported 1844 unique ADRs. BA-fatigue was reported by 100 patients and 48 patients described a consistent pattern of recurring fatigue after each administration. Most of these patients (88%) described recovery from BA-fatigue within one week after biologic administration and 73 patients reported health care professional (HCP) contact following BA-fatigue, with dose adjustment in 8 and discontinuation in 5 patients. Basic demographics and characteristics that differ significantly between patients reporting BA-fatigue and patients not reporting BA-fatigue are summarized in table 1. No significant difference was found for other biologics, IMIDs, combination therapy and comorbidities. BA-fatigue was reported by 27% of rituximab users (n=33), 27% of vedolizumab users (n=26), 16% of tocilizumab users (n=50), 14% of infliximab users (n=159) and 3% of etanercept users (n=418). Although 29 patients in the BA-fatigue population had RA and 29 patients had Crohn’s disease (CD), 571 patients in our overall study population had RA and 194 patients had CD, suggesting BA-fatigue was reported by CD patients more often. The mean burden of BA-fatigue was higher than the mean burden of other ADRs (p&lt;0.001). Table 1. Characteristics of patients with BA-fatigue compared to patients with other ADRs and without ADRs Patients with BA-fatigue n (%) Patients with other ADRs n (%) Patients without ADRs n (%) n 100 (100%) 596 (100%) 673 (100%) Basic demographics Age (years) (mean ± SD) 50.0 ± 14.6 53.4 ± 13.6 * 55.7 ± 14.2 *** Gender (Female) 59 (59%) 398 (67%) ns 342 (51%) ns Smoking n (%) 25 (25%) 97 (16%) * 100 (15%) * BMI (kg/m 2 ) (mean ± SD) 25.7 ± 4.4 25.9 ± 4.7 ns 26.6 ± 5.5 ns Biologic Infliximab 22 (22%) 53 (9%) *** 84 (12%) * Etanercept 13 (13%) 177 (30%) *** 228 (34%) *** Rituximab 9 (9%) 18 (3%) ** 6 (1%) *** Tocilizumab 8 (8%) 29 (5%) ns 13 (2%) ** Vedolizumab 7 (7%) 12 (2%) * 7 (1%) *** IMID Rheumatoid arthritis 29 (29%) 270 (45%) ** 272 (40%) * Crohn’s disease 29 (29%) 77 (13%) *** 88 (13%) *** Other indication 16 (16%) 53 (9%) * 39 (6%) *** Combination therapy Methotrexate 23 (23%) 167 (28%) ns 227 (34%) * Comorbidity Psychiatric disorder 11 (11%) 49 (8%) ns 31 (5%) * Other comorbidity 30 (30%) 124 (21%) * 102 (15%) *** Mean burden of ADR ± SD 2.9 ± 0.9 2.4 ± 1.1 *** Mann Whitney U, independent t-test and Fisher’s exact as appropriate ns: not significant *p ≤ 0.05 **p ≤ 0.01 ***p ≤ 0.001 Conclusion: HCPs should be aware that fatigue may be associated with biologic therapy and has a significant burden on patients. Evaluating the course of the symptoms might be helpful in recognizing BA-fatigue. Disclosure of Interests: Jette van Lint: None declared, Tom Bakker: None declared, Jouke Ubbink: None declared, 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, 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, Harald Vonkeman: None declared, 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, 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, Eugène van Puijenbroek: None declared, Naomi Jessurun: None declared