Assessment of interactions and dosage recommendations of synthetic DMARDs-Evidence-based and consensus-based recommendations based on asystematic literature search

Abstract

Conventional synthetic (cs) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARD) have potential interactions with amultitude 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. Asystematic 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. Atotal of 2756 scientific publications were screened and 154 selected of which 68 were scrutinized in detail. Furthermore, the respective specialist subject information was also analyzed. Amultitude of possible interactions of synthetic DMARDs with different drugs were detected, which were then assessed with respect to the clinical significance and consequences. Aconsensus 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 3primary recommendations and 11core recommendations on interactions and dosages of csDMARDs and tsDMARDs meant as apractical help for therapeutic decision making and to improve safety in the treatment of rheumatoid arthritis.