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What is immunotherapy?
Immunotherapy is a form of treatment, most commonly used against cancer, that targets the body’s immune system. This form of therapy suppresses the immune system which is occasionally responsible for some of the most severe diseases known to man, including cancer. To further understand immunotherapy, we need to review how the body’s immune system works.
The human body has two types of immune mechanisms to fight off diseases. The first type is the innate system which is always active. A good example is the acidic environment in the birth canal that is meant to protect it from harmful organisms which cannot survive in this acidic environment. This mechanism is ever present and active unless it is compromised by a disease.
The second type is known as adaptive immunity. This type is dormant and is activated when the body is exposed to infectious organisms. The two systems are quite complex and work together to keep the body protected. However, the reaction can be excessive and lead to harm. For example, when you have an infection in the lungs, immune cells are recruited to fight off the pathogens. In the process, healthy lung tissue surrounding the infected tissues may also be attacked.
This is exactly what happens in patients with severe COVID-19. The body is flooded with immune cells which start attacking healthy tissues. Thus, part of the treatment for severe COVID-19 will be immunotherapy which prevents this from happening. Studies are already ongoing.
Pregnancy and the immune system
It was previously believed that immunity during pregnancy weakened to prevent the mother’s body from rejecting the fetus. In addition, historically, immunotherapy has not been recommended for pregnant women due to fears that the drugs will cross the placenta to enter the fetus and suppress its immunity.
Now, due to rigorous studies, we have a better understanding of immune physiology in pregnancy. The current consensus is that immunity does not dampen during pregnancy. Instead, it fluctuates throughout the pregnancy to ensure survival of both the mother and fetus. Thus, with this new understanding, the use of immunotherapy in pregnancy cannot be as easily dismissed.
Here are four immunotherapeutic drugs currently undergoing clinical trials for their effectiveness against COVID-19 and their safety profile in pregnancy:
Tocilizumab was developed in Japan in 1997 for the treatment of rheumatoid arthritis. It was approved by the United States Food and Drug Administration (FDA) in 2010 for this indication. It is an immunosuppressive drug that hinders excessive inflammation. It is well tolerated in children and has been used successfully in the treatment of juvenile idiopathic arthritis.
In March 2020, China approved its use in the treatment of severe COVID-19 despite the lack of concrete evidence. A large study is currently ongoing in China. Australia has also allowed its off-label use to be considered in patients who develop Acute Respiratory Distress Syndrome, a complication of COVID-19.
Finally, an Italian physician recently documented a case study where he successfully treated three severe COVID-19 patients with the drug. The FDA has approved a Phase III trial to confirm the effectiveness of tocilizumab and compare it to other treatments in hospitalized patients with severe COVID-19. Hence, it may well be on the verge of approval as treatment for COVID-19.
The use of tocilizumab in pregnancy has not been adequately studied. Only animal studies have been done, and these have shown significant risk of spontaneous abortion. Hence, its use in pregnancy is not likely to be recommended unless the benefits outweigh the risks.
Scientists are on the verge of a breakthrough as far as the treatment of severe COVID-19 with immunotherapy is concerned. While most of these drugs’ effects on pregnancy have not been adequately studied, there is good news. One drug is considered safe, and another is being actively studied precisely on its effects on pregnancy.
Sarilumab is an immunosuppressive drug that was approved by the FDA for the treatment of rheumatoid arthritis in 2017. It has well documented side effects such as lowering the platelet count which increases the chances of bleeding and increasing the risk of infections such as urinary tract infections and oral herpes.
In March 2020, the Feinstein Institute of Northwell Health announced that it was conducting clinical trials on the possible use of sarilumab against COVID-19. The effect of sarilumab on pregnancy is not known. Even so, there is a pregnancy exposure registry that is currently in place. Its aim is to monitor the outcome of women exposed to sarilumab during pregnancy and one year after pregnancy. It currently has three hundred participants.
Emapalumab is an immune modifier that neutralizes a chemical known as interferon gamma. This chemical is pro-inflammatory and plays a role in propagating the body’s immune response even when it may be excessive and harmful. It is FDA-approved for the treatment of primary hemophagocytic lymphocytosis in both adults and children. There is an ongoing trial in Italy investigating its possible efficacy against COVID-19. There is currently no data on its effects on pregnancy.
Anakinra is an immunosuppressive drug that is used as the second line treatment for rheumatoid arthritis. It is also used in neonates with neonatal onset multisystem inflammatory disease. It has been successfully used to treat cytokine storm syndrome, a complication of COVID-19. Further investigations are ongoing.
Its use in pregnancy is currently acceptable. No human studies have been done, but animal studies have found it to be completely safe. Its most common side effects are injection site reactions and headache which occur in 12% of patients.
Scientists are on the verge of a breakthrough as far as the treatment of severe COVID-19 with immunotherapy is concerned. While most of these drugs’ effects on pregnancy have not been adequately studied, there is good news. One drug is considered safe, and another is being actively studied precisely on its effects on pregnancy. As we await more information, let us continue to practice prevention measures that include regular hand washing and social distancing.