Adverse events experienced by people living with chronic rare diseases: A scoping review

Background Rare diseases affect a significant proportion of the global population and largely lack approved treatment options. With subsequent reliance on off-label use, medicine safety monitoring is important. A scoping review was conducted to identify what is known from the current global literature regarding adverse events associated with pharmacological treatments used for chronic rare diseases. Methods The scoping review was conducted according to the Arksey and O’Malley framework, and the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) method. A Boolean search, including “rare disease” and “adverse” or “side effect”, was entered into Scopus, PubMed, Web of Science and Science Direct, to retrieve eligible publications from 2019 to 2024. Results In total, 4570 articles were retrieved and 139 included in the final analysis. Most were from high-income countries, involving biological agents, which were relatively well tolerated by patients. Immunosuppressant prescription was common (particularly corticosteroids), with associated typical adverse event profiles, highlighting the risk of infections. High treatment costs were observed, driven largely by biologicals, especially enzyme replacement therapies. Several articles featured repurposed medicines which varied in cost. Conclusions While newer treatments with improved safety profiles exist, their high cost prohibits access by many persons living with a rare disease (PLWRD), who are affected by long-term, sometimes fatal side effects of older therapies like immunosuppressants. Data is needed from low- and middle-income countries to address disparities in patient experiences. With ongoing safety monitoring, repurposing of medicines provides an important opportunity for progress toward equity for PLWRD.