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  1. L. Roest1,
  2. L. Kosse1,
  3. J. van Lint1,
  4. J. Scholl1,
  5. M. van Doorn2,
  6. S. Tas3,
  7. M. Nurmohamed4,
  8. H. Vonkeman5,6,
  9. R. Hebing7,
  10. P. Spuls8,
  11. F. Hoentjen9,
  12. E. van Puijenbroek10,11,
  13. B. 10,12,
  14. N. Jessurun1
  1. 1Netherlands Pharmacovigilance Centre Lareb, Department of Monitoring, ‘s-Hertogenbosch, Netherlands
  2. 2Erasmus MC, Department of Dermatology, Rotterdam, Netherlands
  3. 3Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, Amsterdam Infection & Immunity Institute and Amsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology & Clinical Immunology, Amsterdam, Netherlands
  4. 4Reade and Amsterdam Rheumatology & Immunology Center (ARC), Department of Rheumatology, Amsterdam, Netherlands
  5. 5Health & Technology, University of Twente, Department of Psychology, Enschede, Netherlands
  6. 6Medisch Spectrum Twente, Department of Rheumatology, Enschede, Netherlands
  7. 7Amsterdam Rheumatology and Immunology Center Location Reade, Department of Pharmacy, Amsterdam, Netherlands
  8. 8Amsterdam UMC, Amsterdam Public Health, Immunity and Infections, University of Amsterdam, Department of Dermatology, Amsterdam, Netherlands
  9. 9Radboud UMC, Department of Gastroenterology, Nijmegen, Netherlands
  10. 10Sint Maartenskliniek, Department of Pharmacy, Nijmegen, Netherlands
  11. 11Netherlands Pharmacovigilance Centre Lareb, Department of Signal Detection, ‘s-Hertogenbosch, Netherlands
  12. 12Radboud UMC, Department of Pharmacy, Radboud UMC, Netherlands


Background: Information on adverse drug reactions (ADRs) is generally clustered for all indications of a drug in the patient information leaflet. However, previous research has shown that participants of the Dutch Biologic Monitor (DBM) that use a biologic for their immune-mediated inflammatory disease (IMID) prefer to receive ADR information tailored to their own biologic an IMID (1). Currently, it is unclear whether the ADR profile of a specific biologic may differ between patients with different IMIDs, which would be vital information for health care providers (HCPs) in their patient guidance.

Objectives: To determine whether the profiles of ADRs attributed to adalimumab (ADA) and etanercept (ETN) reported by patients in the DBM differ between IMIDs.

Methods: The DBM is a prospective cohort event monitoring system for patient-reported ADRs attributed to biologics (2). Study data was extracted from the DBM for the period Jan 2017 – Oct 2020. ADRs were coded according to their corresponding Preferred Term (PT) following MedDRA terminology. Unique PTs were selected per participant and grouped under System Organ Classes (SOCs) (Figure 1) for ADA and ETN. SOCs contributing for <1% to the total number of reported ADRs were grouped as ‘other’. Participants with more than one of the included IMIDs, i.e. Psoriatic Arthritis (PsA), Inflammatory Bowel Disease (IBD, i.e. Crohn’s disease and ulcerative colitis), rheumatoid arthritis (RA), and axial spondyloarthritis (axSpA) including Ankylosing Spondylitis (AS), were excluded.

Differences in ADR profiles between IMIDs were tested using the Fisher-Freeman-Halton’s Exact Test with Monte Carlo simulation. SOCs of interest were separately tested with the Fisher-Freeman-Halton’s Exact Test (no simulation) and subsequently corrected for multiple comparisons using the Benjamini-Hochberg (BH) correction.

Results: A total of 572 ADR reports from 218 participants using ADA and 450 ADR reports from 185 participants using ETN were analyzed (Table 1).

Overall, a statistically significant difference in patient-reported ADR profile between the assessed indications was found for ADA (p=0.011), but not for ETN (p=0.057). The following separate tests for selected SOCs of interest showed a significant difference in the frequencies of ‘respiratory, thoracic and mediastinal disorders’ and ‘musculoskeletal and connective tissue disorders’ between the different IMIDs for ADA after BH correction, but none for ETN.

Figure 1.

The disease-specific patient-reported ADR profile of ADA (A) and ETN (B) in IMID patients resulting from the Dutch Biologic Monitor

Table 1.

The table shows mean±SD, median (IQR) or absolute number (percentage) for all patients included (n=62). RF, rheumatoid factor; ACPA, anti-citrullinated protein antibodies; DAS28, Disease Activity Score-28; csDMARD, conventional synthetic disease-modifying anti-rheumatic drug; MTX, methotrexate; OD, other conventional synthetic disease-modifying anti-rheumatic drugs than methotrexate. The differences between DAS28 groups were analysed considering p-value<0.05 as statistically significant result.

Conclusion: Although only ADA shows a statistically significant difference in ADR profile between different IMIDs, more research with a larger sample size might show similar results for ETN. Furthermore, explanations for the differences found, such as disease-drug interactions, must be examined. This would help HCPs in providing disease-specific information and patient guidance.

References: [1]Kosse LJ et al.; Expert Opin Drug Saf. 2020;19(8):1045-1054.

[2]Kosse LJ et al.; Rheumatol. 2020;59(6):1253-1261

Disclosure of Interests: Lieke Roest: None declared, Leanne Kosse: None declared, Jette van Lint: None declared, Joep Scholl: None declared, Martijn van Doorn Grant/research support from: Leopharma, Novartis, Abbvie, BMS, Celgene, Lilly. Pfizer, Sanofi-Genzyme, Janssen Cilag, all outside the submitted work, Sander Tas Grant/research support from: AbbVie, Arthrogen, AstraZeneca, BMS, Celgene, Galapagos, GSK, MSD, Pfizer, Roche, Sanofi-Genzyme, all outside the submitted work, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Roche, Sanofi, all outside the submitted work, Consultant of: AbbVie, Celgene, Celltrion, Eli Lilly, Janssen, Sanofi, all outside the submitted work, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche, Sanofi, all outside the submitted work, Harald Vonkeman Grant/research support from: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Celltrion, Galapagos, Gilead, GSK, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, all outside the submitted work, Renske Hebing: None declared, Phyllis Spuls Grant/research support from: departmental independent research grant for TREAT NL registry from different companies for the TREAT NL registry, is 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 financial compensation is paid to the department/hospital and, is Chief Investigator (CI) of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children and one of the main investigators of the SECURE-AD registry, all outside the submitted work, Frank Hoentjen Speakers bureau: Abbvie, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz, Dr Falk, all outside the submitted work, Consultant of: Celgene, Janssen-Cilag, all outside the submitted work, Grant/research support from: Dr Falk, Janssen-Cilag, Abbvie, Takeda, all outside the submitted work, Eugène van Puijenbroek: None declared, Bart van den Bemt: None declared, Naomi Jessurun: None declared

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