Safety checklist compiles clinically important DMARD warnings in one place
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Key takeaways:
- Nearly all bDMARDs and tsDMARDs feature infection or malignancy warnings from the FDA or European Medicines Agency.
- A safety checklist can help navigate risks and costs in rheumatology drug selection.
Nearly all biologic and targeted synthetic disease-modifying antirheumatic drugs come with infection or malignancy warnings from U.S. or European regulatory agencies, according to a study published in Drug Safety.
In response to these findings, the researchers development of a safety checklist encompassing clinically important warnings for all biologic and targeted synthetic DMARDs.
“We created the overview that I was never able to find as a rheumatology fellow,” co-author Tue W. Kragstrup, MD, PhD, associate professor at Aarhus University, in Denmark, told Healio. “The contraindications and special warnings are found in the prescribers’ information and on websites about medicinal products. However, this information is typically only partly included in management guidelines from national and scientific societies.”
To create this safety checklist, Kragstrup and colleagues, via systematic overview, collected contraindications, boxed warnings and special warnings for all originator biologic and targeted synthetic DMARDs approved by either the FDA or the European Medicines Agency for rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis and juvenile idiopathic arthritis. The researchers — including first author Lykke Skaarup, MD, a PhD student at Aarhus University — reviewed the extracted data and added “clinically relevant precautions,” such as year of first approval, vaccination responses, mucocutaneous Candida infections and use after TNF inhibitors, they wrote.
“The breadth of data informing a clinical interpretation of drug safety carries inherent uncertainty, which can dynamically increase or decrease over time with new information,” Kragstrup and colleagues wrote. “In this paper, we consider factors that influence the warnings and their clinical interpretation in the context of bDMARDs and tsDMARDs. Some contraindications and warnings in the checklist were therefore downgraded or upgraded on the basis of the current evidence to make it as clear and compelling as possible.”
According to the researchers, the analysis demonstrated contraindications and/or warnings related to infections, including tuberculosis, in all drug classes except phosphodiesterase 4 (PDE4) inhibitors. Malignancy risks were also present in all classes except PDE4 inhibitors, interleukin (IL)-17 inhibitors and IL-23 inhibitors.
Additionally, Kragstrup noted some “surprising” findings, including no major adverse cardiovascular event warning for ustekinumab (Stelara, Janssen), no herpes zoster reactivation warnings for any TNF inhibitors, and no hepatitis reactivation mentioned for IL-17 or IL-23 inhibitors.
The checklist also outlined drugs carrying risks for:
- demyelinating disease (TNF inhibitors, CTLA4-Ig, and IL-6 receptor inhibitors);
- heart failure (anti-CD20 and TNF inhibitors);
- major adverse cardiac events (JAK inhibitors and IL-12/23 inhibitors);
- venous thromboembolism (JAK inhibitors);
- hyperlipidemia (IL-6 receptor inhibitors and JAK inhibitors);
- liver impairment (TNF inhibitors, IL-1 inhibitors, IL-6 receptor inhibitors and JAK inhibitors);
- kidney impairment (IL-1 inhibitors, JAK inhibitors and PDE4 inhibitors);
- inflammatory bowel disease (IL-17 inhibitors);
- gastrointestinal perforation (IL-6 receptor inhibitors and JAK inhibitors);
- cytopenia (anti-CD20, TNF inhibitors, IL-1 inhibitors, IL-6 inhibitors and JAK inhibitors); and
- depression (PDE4 inhibitors).
According to Kragstrup, the checklist will need to be updated on a regular basis as new information emerges. He added that he would also like “to go into more detail with each warning category.”
“This will be a significant tool for rheumatology trainees,” Kragstrup said. “We believe that it will also be a useful addition for many trained rheumatology specialists. It is becoming almost impossible to memorize all warnings for all the new drugs.”
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