- -o-: mouse (all mouse)
- -xi-: chimeric (part human, part nonhuman)
- -zu-: humanized (mostly human, part nonhuman)
- -u-: human (all human)
The target for the mab in the body is usually determined by one or two letters before the source:
Explore This IssueACEP Now: Vol 38 – No 07 – July 2019
- -b(a)-: bacterium
- -s(o)-: bone
- -c(i)-: circulatory system
- -f(u)-: fungus
- -gr(o)-: growth factor
- -k(i)-: interleukin
- -l(i)-: immune system
- -n(e)-: nervous system
- -tox-: toxin
- -t(u)-: tumor
- -vi(r)-: virus
What do emergency clinicians need to know about mabs? First, these drugs cause immunosuppression, predisposing patients to infections. All of the TV ads warn that patients must be checked for latent infections such as tuberculosis or deep fungal infections before starting a mab. Risks of bacterial infections and sepsis are also increased.
Unfortunately, mabs can occasionally cause an array of other side effects, many of which are not likely to be anticipated when only considering their anti-inflammatory effects. These can include:
- New or worsening heart failure
- Blood problems (anemia and pancytopenia)
- Nervous system problems (new or worsening multiple sclerosis and Guillain-Barré syndrome, depression, headaches)
- Paradoxical development of immune disorders, which are often unrelated to the disorder being treated (psoriasis, inflammatory bowel disease, and lupus-like syndromes)
- Weight loss
- Liver abnormalities
- Cancer (lymphomas)
- The usual assortment of minor side effects associated with (but not definitively caused by) most drugs (rash, itching, diarrhea, you name it)
Mabs to Combat Cancer
By far, one of the most miraculous aspects of mabs is their ability to treat cancer. In 2015, former President Jimmy Carter announced that he had malignant melanoma that was in his liver and brain. I figured he was a dead man walking. But four years on, Jimmy Carter is alive and well and still teaching Sunday school in Plains, Georgia. He was treated with a drug called Keytruda (pembrolizumab, a mab from mostly human sources that modulates the immune system). The drug was fast-tracked by the FDA and approved in 2014, and Jimmy Carter got it in 2015.
What do emergency clinicians need to know about mabs? First, these drugs cause immunosuppression, predisposing patients to infections.
Keytruda and another heavily marketed competitor, Opdivo (nivolumab), are the only intensively DTC-marketed drugs for the treatment of cancer. Their commercials don’t talk about cures but rather imply a better (and perhaps longer) quality of life in people with advanced cancer. Commercials typically focus on happy family gatherings. Keytruda had sales reaching $919 million in the first nine months of 2016 alone.1
How do they work? Keytruda and Opdivo are cancer cell uncloaking agents (also called checkpoint inhibitors). Many cancer cells have the ability to “hide” from the immune system, and as such, the body’s own defenses are inhibited from destroying them. More specifically, there are molecules on immune cells that need to be turned on to recognize and attack foreign cells. Cancer cells have the ability to prevent these molecules from being activated. The cancer cells activate what are called checkpoints, and these checkpoints prevent the immune cell from being mobilized. These two drugs inhibit these checkpoints and allow the body’s own immune system to detect and then attack the cancers. Checkpoint inhibitors are often used in conjunction with drugs that boost the immune system, in essence providing a one-two punch. Yervoy (ipilimumab) is one such drug.
The side effect profile of checkpoint inhibitors is markedly different from the anti-inflammatory mabs. Checkpoint inhibitors side effects include: