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Assessment of interactions and dosage recommendations of synthetic DMARDs—Evidence-based and consensus-based recommendations based on a systematic literature search

Bewertung von Wechselwirkungen und Dosierungsempfehlungen von synthetischen DMARDs – Evidenz- und konsensbasierte Empfehlungen auf Basis einer systematischen Literatursuche

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Abstract

Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with a multitude of drugs. Furthermore, they sometimes have a lower therapeutic index, particularly in cases of limited organ functions. The aim of this work was to establish evidence-based recommendations on the therapeutic use of DMARDs in the context of drug interactions and dosage recommendations. A systematic literature search was carried out on the issue of drug interactions and dosages in cases of patients with limited kidney function and higher age and suffering from rheumatoid arthritis. A total of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective product information was also analyzed. A multitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. A consensus process led to making recommendations with which the interactions were classified: A: dangerous combination, B: avoid combination (if possible, pausing DMARD treatment), C: possible combination requiring increased monitoring and potential adjustments in dosage and D: pharmacological interaction without relevance in DMARD standard doses. Apart from that dosage recommendations were established for each csDMARD and tsDMARD depending on kidney function and age. There are 3 primary recommendations and 11 core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as a practical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.

Zusammenfassung

Konventionelle synthetische („conventional synthetic“ [cs]) und gezielte synthetische („targeted synthetic“ [ts]) DMARDs haben potenzielle Wechselwirkungen mit einer Vielzahl von Medikamenten. Darüber hinaus haben sie insbesondere bei eingeschränkten Organfunktionen teilweise eine geringe therapeutische Breite. Ziel der Arbeit war eine systematische Erarbeitung von evidenzbasierten Empfehlungen zur Therapie mit DMARDs im Kontext von Arzneimittelinteraktionen und Dosierungsempfehlungen. Es wurde eine systematische Literaturrecherche zur Frage nach Wechselwirkungen sowie Dosierungen bei eingeschränkter Nierenfunktion und höherem Lebensalter bei rheumatoider Arthritis durchgeführt. Insgesamt wurden 2756 wissenschaftliche Publikationen gescreent und 154 ausgewählt, wobei 68 Publikationen in eine detaillierte Analyse eingingen. Darüber hinaus wurden die Informationen der jeweiligen Fachinformationen analysiert. Es fand sich eine Vielzahl von möglichen Wechselwirkungen von synthetischen DMARDs mit verschiedenen Medikamenten, welche bezüglich klinischer Bedeutung und Konsequenz bewertet wurden. In einem Konsensprozess wurden Empfehlungen erarbeitet, wobei eine Graduierung der Wechselwirkungen erfolgte: A: gefährliche Kombination, B: Kombination meiden (wenn möglich DMARD-Pause), C: mögliche Kombination mit erhöhtem Überwachungsbedarf und evtl. Dosisanpassung, D: pharmakologische Interaktion ohne Relevanz in Standarddosierungen des DMARD. Es wurden darüber hinaus Dosierungsempfehlungen nach Nierenfunktion und Alter für jedes cs- und tsDMARD erarbeitet. Drei übergeordnete Empfehlungen und 11 Kernempfehlungen zu Wechselwirkungen und Dosierung von cs- und tsDMARDs sollen praktische Hilfestellung für therapeutische Entscheidungen geben und die Sicherheit der Therapie der rheumatoiden Arthritis verbessern.

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Authors and Affiliations

  1. Kommission Pharmakotherapie, Deutsche Gesellschaft für Rheumatologie (DGRh), Berlin, Germany

    C. Fiehn, J. Leipe, C. Weseloh, R. Bergner & K. Krüger

  2. Tätigkeitsschwerpunkt klinische Immunologie, Rheumatologie Baden-Baden, Beethovenstr. 2, 76530, Baden-Baden, Germany

    C. Fiehn

  3. V. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany

    J. Leipe

  4. Deutsche Gesellschaft für Rheumatologie (DGRh), Berlin, Germany

    C. Weseloh

  5. Medizinische Klinik A, Klinikum Ludwigshafen, Ludwigshafen, Germany

    R. Bergner

  6. Rheumatologisches Praxiszentrum St. Bonifatius, Munich, Germany

    K. Krüger

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  1. C. Fiehn
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Correspondence to C. Fiehn.

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Conflict of interest

The authors point out the following. C. Fiehn, J. Leipe, and K. Krüger: lecture and/or consulting fees from Abbvie, Galapagos, Lilly, Medac, and Pfizer. R. Bergner: lecture and/or consulting fees from Abbvie and Galapagos. C. Weseloh declares that she has no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

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Fiehn, C., Leipe, J., Weseloh, C. et al. Assessment of interactions and dosage recommendations of synthetic DMARDs—Evidence-based and consensus-based recommendations based on a systematic literature search. Z Rheumatol 83 (Suppl 1), 8–19 (2024). https://doi.org/10.1007/s00393-023-01417-3

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