Tocilizumab (or Actemra) is an IL-6 inhibitor commonly used to treat SJIA and other types of autoimmune and autoinflammatory arthritis. As with all medications, we know that tocilizumab has a variety of side effects. These include lowering blood cell counts, making it easier to catch upper respiratory infections, and allergic reactions (in extreme cases).
Before we dig into the latest study on tocilizumab and hypofibrinogenemia, what in the world is hypofibrinogenemia?
Fibrinogen is a protein that is created in the liver. The body uses this, along with other proteins, to form blood clots and stop bleeding. Depending on how often you’ve run into issues with this protein, you may also know it as Coagulation Factor 1. Blood tests like Factor 1 and serum fibrinogen help monitor the level of fibrinogen in the body, either taking a look at how well the protein is working or what level of the protein is in your blood. Medscape has a really deep dive for those interested.
Generally speaking, hypofibrinogenemia is a rare, inherited blood disorder. They’ve found some responsible chromosomes for this. What hypofibrinogenemia does is present as an abnormality in the quality of fibrinogen, and so it causes issues with blood clotting. Folks with this condition might have things like GI bleeding, excess bleeding following surgeries or procedures, or even events like miscarriages. This can often present as bloody noses that take a long time or are difficult to stop. People may require plasma infusions all the way up to a liver transplant, depending on the severity of this condition. They also have to avoid medications such as NSAIDs that tend to alter bleeding and platelets.
Now, what does this have to do with tocilizumab?
According to a study in Nature, tocilizumab can cause hypofibrinogenemia in SJIA patients. They found that 76.47% of SJIA patients receiving tocilizumab had hypofibrinogenemia. The patients with this condition had a variety of disease activity, including inactive disease, and some were on both methotrexate and prednisone as well. However, those medications were determined to have negligible effects on developing hypofibrinogenemia.
It’s important to note that there was a pretty small number of patients retroactively studied. Around 60% of these patients had no specific symptoms, but some symptoms included bleeding gums and increased bruising. Only one patient studied struggled with nose bleeds.
Why is this happening?
IL-1, IL-6, and TNF all affect fibrinogen. IL-1 and TNF negatively affect it, meaning those of us on IL-1 or TNF inhibitors may receive a boost in our fibrinogen levels due to lower IL-1 and TNF levels. Makes sense, right? Well, IL-6 positively affects fibrinogen. That means IL-6 inhibitors like tocilizumab may cause issues such as hypofibrinogenemia.
Should I be worried?
Worried? No. Proactive? Yes.
First, some notes:
They did test these patients and found they did not have the chromosomes related to hypofibrinogenemia. That means this may not have been an inherited condition for them OR there may be a link between SJIA and this condition that we’re unaware of at the moment.
The researchers admit that this retroactive study with a small number of patients means not enough overall data was collected, so a lot more research needs to be done. They also wondered if there’s a difference for adults versus children when it comes to this, especially since hypofibrinogenemia set in after 1-4 doses of tocilizumab in pediatric patients.
Now, as far as being proactive:
If you or your child is on tocilizumab, it’s worth keeping track of symptoms that may be related – nose bleeds, increased bruising, etc. These could be explained by anemia, which needs to be treated, too. However, it’s worth sharing this study with your rheumatologist to see if they can test your fibrinogen levels if/when they test for anemia as well.
You can read the full study here.