gms | German Medical Science

21. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin e. V.

Deutsches Netzwerk Evidenzbasierte Medizin e. V.

13. - 15.02.2020, Basel, Schweiz

HLA-associated adverse drug reactions – Scoping Review and Analysis of the Swiss Drug Labels

Meeting Abstract

  • Chiara Jeiziner - Universität Basel, Pharmaceutical Care Research Group, Basel, Schweiz
  • Ursina Wernli - Universität Basel, Pharmaceutical Care Research Group, Basel, Schweiz
  • Henriette Meyer zu Schwabedissen - Universität Basel, Biopharmacy Group, Basel, Schweiz
  • Kurt E. Hersberger - Universität Basel, Pharmaceutical Care Research Group, Basel, Schweiz
  • Katja Suter - Universität Basel, European Center of Pharmaceutical Medicine, Basel, Schweiz

Nützliche patientenrelevante Forschung. 21. Jahrestagung des Deutschen Netzwerks Evidenzbasierte Medizin. Basel, Schweiz, 13.-15.02.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. Doc20ebmPP6-04

doi: 10.3205/20ebm092, urn:nbn:de:0183-20ebm0924

Published: February 12, 2020

© 2020 Jeiziner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background/research question: Drug labels (DLs) provide information on genetic polymorphisms influencing drug safety and efficacy and instructions on pharmacogenetic (PGx) testing. No specific section is dedicated to PGx. However, the instructions on PGx often insufficiently support the decision-making process of health care professionals (HCPs). Moreover, the HCPs have to cope with the uncertainty about the underlying data. In our Scoping Review (ScR) we focused on Human Leucocyte Antigene (HLA)-associated adverse drug reactions (ADRs). The aim was to provide a literature overview of active substances with known HLA-associated ADRs and to analyze the information presented in the DL.

Methods: We conducted a literature research according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) [1]. The search consisted of three clusters (HLA, ADR, and active substances) and was elaborated together with an information specialist. We included studies describing an association of an HLA-associated ADR with an active substance currently registered in Switzerland. We considered English and German primary literature published since 2002. For exact study results of the indications in the DL, we contacted the corresponding companies. We compared the descriptive results with the PGx information in the DL of the active substances containing such.

Results: Of the 1677 studies identified in Embase® and PubMed, 136 studies were included, reporting on 24 individual active substances and 4 substance groups currently approved in Switzerland. For abacavir, we identified a prospective randomized controlled trial [2]. However, most of the included studies were retrospective. Carbamazepine-induced cutaneous drug reactions due to HLA-B*1502 were the most frequent. In abacavir, allopurinol, carbamazepine, oxcarbazepine, and phenytoin, we identified underlying literature for the presented information in the DL. The evaluated evidence of HLA-associated ADRs for lapatinib, pazopanib, and flucloxacillin was not consistently represented in the DLs.

Conclusion: The studies identified by ScR were very heterogeneous, hence giving a rough overview of the evidence available and showing the limitations of the research on HLA-associated ADRs. With this ScR we would like to stimulate the discussion on how new research findings should be integrated into the DL to support HCPs in their decision-making and patient counselling – especially in the emerging field of treatment individualization by PGx testing.

Competing interests: none


References

1.
Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D, Moher D, Peters MDJ, Horsley T, Weeks L, Hempel S, Akl EA, Chang C, McGowan J, Stewart L, Hartling L, Aldcroft A, Wilson MG, Garritty C, Lewin S, Godfrey CM, Macdonald MT, Langlois EV, Soares-Weiser K, Moriarty J, Clifford T, Tunçalp Ö, Straus SE. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation. Ann Intern Med. 2018 Oct 2;169(7):467-473. DOI: 10.7326/M18-0850. External link
2.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jägel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A; PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008 Feb 7;358(6):568-79. DOI: 10.1056/NEJMoa0706135 External link