All biologic disease-modifying antirheumatic drug (DMARD) classes, except phosphodiesterase 4 inhibitors, may carry significant warnings related to infections, including tuberculosis, according to a recent systematic review.
In the systematic review, published in Drug Safety, investigators compiled a comprehensive list of contraindications and special warnings for biologic and targeted synthetic DMARDs. They aimed to establish a framework for a prescription safety checklist to improve the safe use of these medications.
The review analyzed data from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for biologic DMARDs and targeted synthetic DMARDs indicated for rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis. The drug classes included anti-CD20, tumor necrosis factor (TNF) inhibitors, interleukin (IL-1, IL-6R, IL-12/23, IL-17, IL-23) inhibitors, cytotoxic T-lymphocyte-associated protein 4 (CTLA4-Ig), Janus kinase (JAK) inhibitors, and phosphodiesterase 4 (PDE4) inhibitors. The analysis utilized data from the EMA's Summary of Product Characteristics and the FDA's Prescribing Information to provide a thorough review of approved warnings and contraindications.
Key findings revealed that all drug classes, except PDE4 inhibitors, had contraindications or warnings related to infections, including tuberculosis. Anti-CD20, IL-1 inhibitors, IL-6 receptor inhibitors, and JAK inhibitors carried warnings for herpes zoster. Warnings for hepatitis reactivation are noted for anti-CD20, TNF inhibitors, IL-1 inhibitors, CTLA4-Ig, IL-6R inhibitors, and JAK inhibitors. Most drug classes, excluding PDE4 inhibitors, IL-17 inhibitors, and IL-23 inhibitors were associated with malignancy risks. Other notable warnings included:
- Demyelinating disease: TNF inhibitors, CTLA4-Ig, IL-6R inhibitors
- Heart failure: anti-CD20, TNF inhibitors
- Major adverse cardiac events: JAK inhibitors, IL-12/23 inhibitors
- Venous thromboembolism: JAK inhibitors
- Hyperlipidemia: IL-6R inhibitors, JAK inhibitors
- Liver impairment: TNF inhibitors, IL-1 inhibitors, IL-6R inhibitors, JAK inhibitors
- Kidney impairment: IL-1 inhibitors, JAK inhibitors, PDE4 inhibitors
- Inflammatory bowel disease: IL-17 inhibitors
- Gastrointestinal perforation: IL-6R inhibitors, JAK inhibitors
- Cytopenia: anti-CD20, TNF inhibitors, IL-1 inhibitors, IL-6R inhibitors, JAK inhibitors
- Depression: PDE4 inhibitors
The investigators observed that the number of contraindications and warnings for these drugs often grew over time following their approval, emphasizing the need for continuous postmarketing surveillance. The findings suggested that a standardized prescription safety checklist could assist physicians in making informed decisions regarding the use of biologic DMARDs and targeted synthetic DMARDs. As new data emerges, the checklist can be updated to reflect current safety information, aiming to optimize patient care and mitigate potential risks associated with these therapeutic agents.
Full disclosures can be found in the published study.
