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  1. Jette van Lint1,
  2. Naomi Jessurun1,
  3. Sander W. Tas2,
  4. Harald Vonkeman3,
  5. Bart van den Bemt4,5,
  6. Astrid van Tubergen6,
  7. Michael Nurmohamed7,8,
  8. Eugène van Puijenbroek1,9
  1. 1Netherlands Pharmacovigilance Centre Lareb, ‘s-Hertogenbosch, Netherlands
  2. 2Amsterdam University Medical Centers, location AMC, Rheumatology and Clinical Immunology, Amsterdam, Netherlands
  3. 3Medisch Spectrum Twente, Rheumatology and Clinical Immunology, Enschede, Netherlands
  4. 4Sint Maartenskliniek, Nijmegen, Netherlands
  5. 5Radboudumc, Nijmegen, Netherlands
  6. 6Maastricht UMC+, Rheumatology, Maastricht, Netherlands
  7. 7Amsterdam Rheumatology and Immunology Center Reade, Amsterdam, Netherlands
  8. 8Amsterdam University Medical Centers, location VUMC, Rheumatology and Clinical Immunology, Amsterdam, Netherlands
  9. 9University of Groningen, Research Institute of Pharmacy, Groningen, Netherlands


Background: Numerous biological DMARDs (bDMARDs) are used in RA treatment, however detailed knowledge of patients’ perceptions on drug use and the impact of adverse drug reactions (ADRs) is sparse.

Objectives: To gain insight into bDMARD-induced ADRs and their burden from the RA patients’ perspective.

Methods: The Dutch Biologic Monitor is an ADR-patient web-based questionnaire used for a prospective, multicentre, event monitoring cohort study including patients using a bDMARD for an immune-mediated inflammatory disease between January 1, 2017 and December 31, 2018. Patients were asked to complete questionnaires bi-monthly about used bDMARDs, indication and bDMARD-induced ADRs. ADRs were coded according to MedDRA terminology and their impact was measured on a 5-point scale, ranging from 1 (no burden) to 5 (very high burden). Per patient, every recurrent unique ADR was included as one ADR. ADRs regarding infections (INF), skin (SK), gastrointestinal (GI) and injection site (INJ) were clustered and analysed for the reported prevalence and burden. Fatigue and headache were separately analysed for prevalence and burden. The prevalence of clustered ADRs between the various bDMARDs was compared using a χ2-test and the average burden was compared using a Mann-Whitney U test.

Results: In the Dutch Biologic Monitor 583 consecutive (44.8%) RA patients were included (71.2% female, average age 59 years, SD±12.4) using the originator or a biosimilar of etanercept (ETN, 265), adalimumab (ADA, 196), tocilizumab (41), abatacept (35), certolizumab pegol (23), rituximab (19), infliximab (18), golimumab (15), sarilumab (2), secukinumab (1), anakinra (1). Almost half of the patients (276; 47.3%) reported at least one bDMARD-induced ADR with a total of 703 ADRs in 2,559 completed questionnaires. Patients reported 129 INJ reactions (129 ADRs/583 pts, prevalence of 22.1%, reported by 86 pts) with an average burden of 1.7 (SD±0.8), 57 GI reactions (9.8%, 41 pts) with an average burden of 2.9 (SD±1.1), 102 SK reactions (17.5%, 64 pts) with an average burden of 2.9 (SD±1.1) and 109 INFs (18.7%, 79 pts) with an average burden of 3.3 (SD±1.0). Prevalence of INJ and GI reactions was significantly higher among ETN users than among ADA users (INJ: 76 ADRs/265 ETN users (28.7%) vs 30 ADRs/196 ADA users (15.3%), P=0.007; GI: 30/265 (11.3%) vs 9/196 (4.6%), P=0.01). The prevalence of INFs and SK reactions did not differ. The perceived burden of GI reactions was higher for ETN than for ADA users (3.1 ±1.0 vs 2.0 ±0.7, p=0.006) but did not differ for other clustered ADRs. The number of patients using other bDMARDs was too low for further analysis. Prevalence of bDMARD-induced headache was 1.9% (12 ADRs/583 pts) with an average burden of 3.4 (SD±0.9). Prevalence of bDMARD-induced fatigue was 4.3% (25 ADRs) with an average burden of 2.7 (SD±1.0).

Conclusion: Almost half of the RA patients reported bDMARD-induced ADRs. From the patients’ perspective INJ reactions have the highest prevalence with a relatively low burden, whereas INFs and headache are less prevalent but give the highest burden of the analysed ADRs. Further studies are required to obtain more insight into the perceived differences in ADRs between bDMARDs.

Disclosure of Interests: Jette van Lint: None declared, Naomi Jessurun: None declared, Sander W. Tas: None declared, Harald Vonkeman: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer, Abbvie; Speakers bureau: Pfizer, AbbVie, UCB, Biogen, Sandoz, Consultant for: UCB, Novartis and Pfizer, Astrid van Tubergen: None declared, Michael Nurmohamed Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Eugène van Puijenbroek: None declared

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