Analysis and visualization of the course and burden over time of adverse drug reactions (ADRs) attributed to TNFα-inhibitors in patients with inflammatory rheumatic diseases (IRDs)

ABSTRACT

Background

We aimed to investigate course and burden over time of ADRs attributed to TNFα-inhibitors in IRD-patients, and whether Sankey diagrams and polar plots can visualize this.

Research design and methods

Data on ADRs experienced during the Dutch Biologic Monitor (January 2017 till December 2022) were used in this study. We selected IRD-patients using a TNFα-inhibitor, reporting skin reactions/infections/injection site reactions and completing ≥3 questionnaires (i.e. the initial report and ≥2 follow-ups). Course was scored as worsening/improving/remaining stable/resolving and as (non-)recurrent. Patients scored burden from 1 (no burden) to 5 (very high burden). Sankey diagrams and polar plots visualized this.

Results

202 patients were included, reporting 353 ADRs. Most skin reactions were stable (25.0%). Most infections resolved (50.8%). Injection site reactions were mostly recurrent (72.3%). Skin reactions and infections tended to decrease in burden . Infections had highest burden at start, which mostly decreased over time. Injection site reactions had a low and stable burden.

Conclusions

Skin reactions attributed to TNFα-inhibitors by IRD-patients are stable with a slightly decreasing burden over time. Infections have highest burden at start but resolved mostly. Injection site reactions have a low and stable burden. Sankey diagrams and polar plots are suitable to visualize this.

KEYWORDS:

• Adverse drug reaction
• course
• burden
• polar plots
• Sankey diagrams

Declaration of interests

PI Spuls has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid), receives departmental independent research grants for TREAT NL registry, for which she is Chief Investigator (CI), from pharma companies since December 2019, 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. MBA van Doorn reports grants from Novartis; consulting fees or honorarium from Leopharma, Novartis, Abbvie, BMS, Celgene, Janssen-Cilag, Lilly, MSD, Pfizer and Sanofi-Genzyme; support for travel, manuscript preparation or other purposes from Sanofi-Genzyme, Novartis and Pfizer; payment for lectures from Leopharma, Novartis, Janssen-Cilag and Pfizer, all outside the submitted work. F Hoentjen has served on advisory boards or as speaker for Abbvie, Janssen-Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk. He reports grants from Dr. Falk, Janssen-Cilag and Abbvie and consulting fees from Celgene, all outside the submitted work. MT Nurmohamed has received payment as a speaker or consultant of Abbvie, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Janssen, Roche and Sanofi, all outside the submitted work. He reports financial grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche, Galapagos and Sanofi, all outside the submitted work. SW Tas has worked as a paid consultant for Gebro, GSK, AbbVie, Galvani, Arthrogen and Galapagos, all outside the submitted work. He reports financial grants from Pfizer, GSK, Celgene, BMS, Sanofi and AstraZeneca, all outside the submitted work. HE Vonkeman has worked as a paid consultant for AbbVie, Amgen, AstraZeneca, BMS, Celgene, Celltrion, Galapagos, Gilead, GSK, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, Roche and Sanofi-Genzyme, all outside the submitted work. He reports financial grants from AbbVie and Sanofi, both outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics approval

Ethical approval was waived for the Dutch Medical Research Involving Human Subjects Act (WMO) by the Medical Research Ethical Committee of Brabant, the Netherlands (file number: NW2016-66). The Dutch Biologic Monitor was approved by the medical ethics committees of the participating hospitals. All participants received information about the Dutch Biologic Monitor prior to participation and signed a digital informed consent form.

Author contributions

Conception and design, M de Boer and NT Jessurun; Data analysis, M de Boer; Writing—original draft, M de Boer, NT Jessurun, J Jansen and HR Gosselt; Writing—review & editing, M de Boer, NT Jessurun, HR Gosselt, J Jansen, MBA van Doorn, F Hoentjen, MT Nurmohamed, PI Spuls, SW Tas and HE Vonkeman.

Data availability

The dataset analyzed during the current study is available from the corresponding author upon reasonable request.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2022.2110237

Additional information

Funding

The Dutch Biologic Monitor work was supported by the Netherlands Organization for Health Research and Development (ZonMw) [grant number 848050005]. No funding was received for this study.