The safety of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis

ABSTRACT

Introduction: Tumor necrosis factor inhibitors (TNFi) were the first biologic therapy authorized for rheumatoid arthritis (RA) treatment and are currently the most used biological drugs in these patients. Although clinical efficacy is proven, adverse events associated with these agents have been described, and further knowledge is essential to facilitate detection at very early stages.

Areas covered: We reviewed the safety profile of TNFi, including both articles and congress communications published on this topic, such as clinical trials, meta-analyses, observational studies, data from registries, and spontaneous clinical reports. We classified studies according to the most common and relevant adverse events associated with TNFi.

Expert opinion: There is a broad spectrum of possible adverse events associated with TNFi treatment, ranging from mild to serious, and with diverse clinical manifestations. However, most adverse events may be minimized by appropriate screening before starting treatment and with ongoing surveillance to ensure an early diagnosis. In conclusion, TNFi have a reasonable safety profile, and, globally, the benefits far outweigh the possible risk of adverse events, especially compared with the risk of the untreated underlying inflammatory condition.

KEYWORDS:

• Biological therapy
• TNF antagonists
• adverse events
• drug risk

Article highlights

• This article reviews the safety profile of TNFi which have been used for more than 15 years in patients with RA.

• After an introduction analyzing the reporting of adverse events, a structured analysis of the most relevant adverse events associated with TNFi is made.

• A wide variety of adverse events are associated with TNFi treatment, ranging from mild to serious and with differing clinical findings and prognoses.

• The main TNFi adverse events requiring caution are infections, including opportunistic infections and the risk in patients with chronic infections. Other safety concerns are the risk of malignancy, of demyelinating disease, the cardiovascular risk, and the risk in pregnancy.

• Appropriate screening before starting TNFi treatment may minimize some adverse events, and correct surveillance during treatment may allow an early diagnosis of possible adverse events.

• TNFi have a reasonable safety profile, especially when recommendations and controls are followed, and their benefits outweigh the risks, especially compared with the risk of the untreated underlying inflammatory condition.

This box summarizes key points contained in the article.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.