Monoclonal Antibodies and the Importance of Adverse Event Monitoring 

By Boris Zhang, PharmD; Radhika V. Kumar, PhD, MS 

Boris Zhang, Adjunct Faculty (Department of Clinical and Administrative Sciences) 

Radhika V. Kumar, Assistant Professor (Department of Pharmaceutical Science) 

Pharmacovigilance is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem as defined by World Health Organization (WHO). While it may be easy to overlook medications that have been around for decades, newer medications, especially those treating more serious diseases, should be monitored more vigilantly. The clinical drug trial and approval process occurs in four phases, I II, III and IV respectively. Phase IV involves the post-marketing monitoring period of the new drug for unexpected side effects or additional, approval for populations outside of the original intended population or special populations. The time span of Phase IV is highly variable depending on the frequency of occurrence, magnitude, intensity of detectable side effects. When they do occur, it takes a long time to collect the data and write a full research article; hence reporting summarized case studies is an easier and convenient way keeping in mind continually educating and updating healthcare professionals in a timely manner.  

Monoclonal Antibodies (mAbs), a recent evolution in the area of targeted drug therapy, has  been proven to be effective in the treatment of various disorders. The first FDA approved mAb was muromonab-CD3, a CD3 T-cell inhibitor, used for transplant rejection. By 2014, there were approximately 30 FDA approved mAbs therapies on the market. With the rapid progression of technology and incentives to dive into this field, more mAbs are being tested in drug pipelines for indications including but not limited to cancers, rheumatoid arthritis, and a variety of immune system conditions. It is expected for the mAB market to grow by 300% between 2020 and 2023 and bring in a gross revenue around $524.68 billion. With these medications being one of the most expensive medications in pharmacy formularies, it is hard to see why companies would not invest in this ever-growing field. 

Putting profits aside, it’s important to note that due to the infancy of this class of medications, rare side effects continue to pop up in case studies. One example is the combination of ipilimumab and nivolumab for the treatment of cancers like melanoma and metastatic renal cell carcinoma. Between 2021 to 2022, several case studies have documented adverse reactions affecting multiple organ systems. An 81-year-old male in Japan developed myocardial damage on this regimen while a fatal case of cardiac arrythmia was reported in a 66-year-old female in the United States. Enteritis was reported in a 62-year-old male in France, and sarcoid-like reactions were reported in a 54-year-old female from China. While monoclonal antibody treatments show a lot of favorable outcomes in their clinical trials, these case studies remind us that the long-term effects can still surprise us with unexpected adverse reactions. As healthcare providers, we should continue to not only review our current knowledge but update ourselves on newer side effects as monoclonal antibodies continue to flood the therapeutic market. 

Liu J. The history of monoclonal antibody development – Progress, remaining challenges and future innovations. Ann Med Surg (Lond). 2014 Dec; 3(4): 113-116. doi: 10.1016/j.amsu.2014/09.001 

Precedence Research. Monoclonal Antibodies Market Size to Hit US$ 524.68 Bn by 2030. GlobeNewswire. Updated May, 2022; Accessed 11/2/2022. www.globenewswire.com/news-release/2022/05/23/2448585/0/en/Monoclonal-Antibodies-Market-Size-to-Hit-US-524-68-Bn-By-2030.html 

Zhang B., Kumar RV., Ray S. Side effects, toxicity and ADRs of monoclonal antibodies in multiple organ systems. SEDA. 2022; 1-14. doi: 10.1016/bs.seda/2022.09.008