Analysis of adverse drug reactions in the treatment of rheumatological diseases with biological medicinal products – a systematic review of scientific publications

To analyze reports of adverse drug reactions (ADRs) occurring during and after treatment of rheumatologic diseases with biological medicinal products (BMPs), published in the scientific literature; to determine the type, frequency, grade of severity and evaluate the causality with the ongoing treatment. The literature search was conducted in MEDLINE and PubMed databases for the period from November 2002 to November 2016. We found 710 publications, and 225 papers were selected for data extraction. We carried out descriptive and variational analyses as basic statistical analyses. We defined mean values, standard deviation, minimum, maximum, 95% confidence intervals. We assessed the results using PICOS instrument – population, intervention, comparison, outcomes and study design. The analyzed population included 137,564 patients with rheumatic diseases. Original articles and reviews account for the largest share of publications - 183 (81.33%). The most frequently used medicinal products were monoclonal antibodies. We found data of 284 types of ADRs. The most commonly reported ADRs were: common infections, development (activation) of tuberculosis infection, malignancies. ADRs were found in 12,979 patients, i.е. in 9,43% of the population, there was at least one ADR. Our systematic review has shown increased interest in the pharmacovigilance of biological medicinal products. The larger share of scientific publications, however, use non-standardized terminology to describe ADRs, which is not in line with the current pharmacovigilance concept. Ignorance of the notions, inaccurate and incorrect handling of scientific-regulatory terminology, and errors in ADRs reporting and publication in scientific literature do not allow for systematic reviews in this field.