Ancillary Medications Drive More Adverse Drug Effects in Rheumatologic Disorders Than DMARDs: Study

To adequately evaluate the extent of the problem of drug-related issues, a comprehensive retrospective cohort study was conducted at a large tertiary referral center by studying electronic medical records covering a 14-year observation period from 2010 through 2024. For the analysis, patients were selected among adults diagnosed with one of the six specific types of primary autoimmune rheumatic conditions, namely, ankylosing spondylitis (AS), psoriatic arthritis (PsA), rheumatoid arthritis (RA), Sjögren’s disease (SjD), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To confirm true cases of adverse drug events, specialists used validated criteria, whereas prescribed drugs were classified according to their Anatomical Therapeutic Chemical classes.

For active exposure, the definition entailed that a person had been prescribed the medication in question during the 30-day period prior to their visit. Polypharmacy involved two subcategories: minor (5-10) and major (>10) number of concomitant medicines. To identify exact medication effects on the likelihood of developing an adverse drug event, specialists performed nested case-control studies with 4 matched controls per ADE case in relation to the kind of medical visits and calculated aORs using conditional logistic regression models.

Key findings:

• The multiyear retrospective study included a total sample of 10,578 adult patients diagnosed with primary autoimmune rheumatic diseases.
• Among the total sample size, 3,154 patients (29.8%) suffered from at least one reported adverse drug event during the study period.
• The prevalence rates of side effects were not uniform for all the disease groups and varied from 35.9% among systemic sclerosis patients.
• Drug prescription was common among all subjects, and 57.3% of the patients had to take several drugs concurrently that could be classified as minor polypharmacy, and 39.4% of the sample demonstrated major polypharmacy.
• The average number of drugs per patient was two times more in cases with complications; lupus outpatients had to take 12 versus 6 drugs, and hospitalized patients required a double increase in terms of drug consumption, namely 20 versus 10.
• The application of metoclopramide – gut motility drug – caused a tremendous increase in complications with an aOR value of 12.32 among patients with systemic sclerosis.
• Ankylosing spondylitis patients complained about severe side effects induced by ciprofloxacin (aOR = 13.71) and fluticasone (aOR = 8.88).

ADEs impact nearly a third of patients with ARD and are correlated positively with the number of drugs used. The risk of ADEs is concentrated in symptom-targeting medications rather than DMARDs. This analysis provides a significant insight into long-term treatment of arthritis, which demonstrates the need to protect the patient not only from the disease but also from its treatment.

Reference:

Lewis, A. A., Huang, C.-Y., Cragun, J., Vuong, L., Irani, A., Anastasiou, C., Bozkurt, S., Donneyong, M., Garg, S., Groenewald, C. B., Weisman, M., & Falasinnu, T. (2026). Adverse drug events across autoimmune rheumatic diseases: A nested, encounter-matched case-control study. In medRxiv. https://doi.org/10.64898/2026.05.19.26352957