Safety profile of biological therapies for treating rheumatoid arthritis

ABSTRACT

Introduction: Biological agents such as tumor necrosis factor inhibitors (TNFi), abatacept, rituximab and tocilizumab have proven efficacy in RA. However, these agents are also associated with adverse events so further data is essential to detect them at the earliest stage possible.

Areas covered: Herein, the authors review the safety profile of biological therapy, including TNFi and non-TNF agents including abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ). The authors analyze both published articles and congress communications including clinical trials, meta-analyses, observational studies, data from registries and spontaneous clinical reports. The authors classify studies according to the most common and relevant adverse events associated with biological agents.

Expert opinion: Biological therapies have a reasonable safety profile and, globally, the benefits far outweigh the possible risk of adverse events. Currently, the risk of serious infections is low and no increased risk in solid malignancies or cardiovascular events have been found after a long clinical experience with these therapies. However, there are still potential risks as well as concerns of immunogenicity induced by TNFi. More studies are required to understand these risks, design safer drugs, and implement pharmacogenomics into the clinic. This will lead to a more personalized medicine in the future.

KEYWORDS:

• Biological therapy
• TNF antagonists
• abatacept
• rituximab
• tocilizumab
• adverse events
• drug risk

Article highlights

• Infections, mainly bacterial, are the most frequent adverse events of biological therapy. Under the current management of these therapies, the risk of severe infections has become low. ABA has better safety profile than other biological agents and might be the drug of choice for patients at high risk of infection.

• Opportunistic infections, most frequently reactivation of latent TB, have been associated with TNFi, especially monoclonal antibodies, while ABA shows a lower risk. Screening for latent tuberculosis infection is mandatory in all patients prior to initiation of all biological drugs.

• Screening for Hepatitis B infection is recommended before starting biological therapy and Rituximab should be avoided in those patients with active or occult B hepatitis. Consider hepatitis B vaccination if patient has not been exposed.

• Flu and pneumococcal vaccination are recommended in all RA patients before starting biological therapy. If live vaccines are needed, they should be administered before starting biologic therapy.

• No increased risk of malignancy has been associated with biological therapy, but it is not recommended in patients with active malignancy in the last 5 years, with the exception of Rituximab.

• TNFi and non-TNFi biological therapy have not been associated with higher CV risk. However, TNFi should be avoided in patients with heart failure.

• TNFi monoclonal antibodies are associated with immunogenicity, which can result in fading of efficacy. Their combination with MTX can reduce this risk, which is lower for etanercept and non-TNFi biologic therapies. ANA and other autoantibodies have also been detected in patients receiving biological therapy, but no specific clinical phenotypes have been reported

• TNFi exposure in pregnancy is not associated with congenital abnormalities. CZP may be used throughout pregnancy as it does not cross the placental barrier. Teratogenic risk not seems relevant with non-TNFi, but it is recommended to discontinue these drugs 3-6 months before conception.

• TNFi have been associated with demyelinating disease. Although this adverse event is very infrequent and not well understood, TNFi are not recommended for patients with personal or family history of demyelinating disease.

• TCZ is associated to higher risk of lower intestinal perforation compared with other biological therapies. It should be avoided in patients with a history of diverticulitis.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank David Buss of Brandt New Agency for their professional language editing help.

Declaration of interest

JD Canete has received fees for expert advisory and/or academic presentations from AbbVie, Novartis, Eli Lilly and Company, Janssen Pharmaceuticals, Pfizer Inc and Celgene. MV Hernandez has received fees from academic presentations from UCB, Roche and Pfizer Inc. Finally, R Sanmarti has received fees for expert advisory and/or academic presentations from Roche, AbbVie, Pfizer Inc, Eli Lilly and Company, Bristol-Myers Squibb and UCB. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This manuscript has not been funded. The authors have no other 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 apart from those disclosed