Impact of adverse events associated with medications in the treatment and prevention of rheumatoid arthritis

Purpose: Treatments for rheumatoid arthritis (RA) over the last few decades have transformed the future outlook of the disease. Patients with clinically apparent RA have a number of therapeutic options; however, all are associated with the risk of adverse events (AEs). Such therapeutics, facilitated by the identification of novel biomarkers, environment and genetic factors to predict RA may allow early detection, prompt treatment and prevention prior to developing clinically apparent disease in the future. However prior to choosing such treatments, to make informed decisions accurate quantification of benefits and harms of such treatments is vital for participants without symptoms but at high risk of developing RA is imperative. This review therefore summarises the AEs reported in trials in pre-clinical or very early RA, the primary AEs of concern associated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), high cost drugs such as biologics, glucocorticoids and analgesia in clinically apparent RA and evidence to date to support the quantification of benefit/harms incorporating patient preferences.
Methods: This is a narrative review in which we performed individual searches in PubMed and EMBASE for each drug and topic outlined in the review.
Findings: Current therapies in RA can result in a considerable burden of AEs (serious and non-serious) depending on the individual’s baseline risk. The absolute risk of serious AEs to treatments reported in pre-clinical RA, undifferentiated or very early inflammatory arthritis trials was low, however non-serious AEs were not consistently reported. If such therapies prove effective at preventing the onset of RA in high risk patients, incorporating patient preferences as well as robust quantification of benefits/ harms to inform decisions is imperative. Patients’ perceptions about treatment in this context may be risk averse or benefit driven. Risk of AEs that may not reverse following drug cessation, such as serious infection and malignancy appear to be important AEs in such decision making.
Implications: The impact of AEs in response to potentially preventative treatment is an important consideration for individuals at high risk of developing RA with minimal symptoms. Robust quantification of treatment effect given baseline risk vs. the risks of developing all AEs, including those that may affect quality of life, whilst incorporating participants’ views will be necessary for future informed decision making.