Biologics explained

Biological medicines, or biologics, get talked about a lot. The word is casually thrown around in the rheumatology world by doctors and patients alike. What can get skipped, though, is an explanation of what, exactly, makes a biologic a biologic, and why biologics are different from other drugs.

What is a biologic?

A biologic medication is a medication that comes from a living source. The drug is produced by living cells and then used as medicine. This is different from traditional medications, like aspirin, Tylenol, or ibuprofen, which can be made by carefully combining chemicals (I’ve even made aspirin myself in lab class). Because of how biologics are made, the structures are highly complicated and can’t be easily mapped. This is why they’re so expensive, and why generic biologics don’t exist (but biosimilars do).

Biologics include arthritis medications like Humira, Enbrel, Remicade, and Cosentyx. They also include cancer drugs, insulin, and vaccines. Since they come from living things, biologics have to be kept in very specific conditions so that they work properly. Proper temperatures and protection from light are usually important. They’re often given by injection or infusion. (Don’t worry, companies spend a lot of time making them easy to use and not painful.)

How biologics work for arthritis

Inflammatory arthritis happens when the immune system targets things it’s not supposed to—in this case, the joints. There are a lot of factors that go into the immune response, mostly a lot of proteins that signal to other proteins with chemical messengers. These chemical messengers eventually cause the inflammation that leads to pain and damage from arthritis.

Generally, biologics used to treat arthritis are antibodies to these proteins and chemical messengers. They attack the proteins and messengers so that they can’t do their jobs properly, which reduces inflammation where it’s not supposed to be. It can also reduce the immune system’s effectiveness in places where it is supposed to be, so this is why biologics can make you more at risk for infections.

Humira, Enbrel, and Remicade, for example, bind to TNF-α. (Tumor necrosis factor alpha is an immune system signal protein. It can cause inflammation as well as fevers and cell death, and it can help stop viruses and sepsis.) More recent biologics approved for arthritis, like Cosentyx, target different messengers called interleukins (ILs) that also promote inflammation. Each biologic works slightly differently, so if one doesn’t work or stops working, another might still help.

The history of biologics for arthritis

Biologic medications have been in use for a long time for some diseases. For example, insulin to treat diabetes was first discovered in the 1920s. (And prior to that, type 1 diabetes was a death sentence.) Biologics for arthritis treatment didn’t get to us until the late 1990s, though.

For a long time, the best arthritis treatments were anti-inflammatory drugs such as corticosteroids (e.g. Prednisone) and NSAIDs (e.g. Advil, Aleve). Another common treatment that might seem bizarre to us today was gold injections. These drugs don’t stop arthritis from progressing, though—they only treat the symptoms, and sometimes very poorly. People with arthritis would often wind up with extensive joint damage and deformities as the disease progressed.

The next class of drugs used for arthritis treatment were named DMARDs (disease modifying anti-rheumatic drugs) for the belief that they would change the course of the person’s disease. Early DMARDs were often poorly tolerated by patients so couldn’t be used for long periods of time, and they didn’t provide permanent, drug-free relief from arthritis. A later DMARD, methotrexate (FDA approved 1988), was one of the first that could be tolerated for long periods (although not by all people). It still didn’t offer drug-free remission, but it could keep disease very well controlled for many people. Methotrexate is still used today as an effective treatment, especially for rheumatoid arthritis.

Animals that had excessive TNF were the first hint that TNF might play a role in arthritis development, which was discovered in 1991. Enbrel was the first biologic approved for arthritis, in 1998. (Remicade was actually approved a few months beforehand, but not originally for arthritis.) Humira followed several years later, in 2002, and it’s since become the world’s top-selling drug. Biologics can stop disease progression and put arthritis into remission in some cases, and they don’t have the debilitating side effects seen in some DMARDs (although infections are a concern). The extensive research and production that goes into each biologic medication is the reason for their high cost.

Some science-y “fun” facts

One problem with anything that enters the body is that the immune system will attack it if it thinks it doesn’t belong. This can be true even when it’s a biologic meant to turn parts of the immune system off. This is why some biologics don’t work for some people, and why sometimes they stop working after awhile. The immune system finally builds up a defense against them, and they’re destroyed before they can work.

Biologics can come from a lot of different sources. For biologics used for arthritis, it’s usually human DNA, mouse DNA, or a combination. The drugs that work best for getting past the immune system have more human DNA, because this keeps the immune system from thinking they’re invaders. Humira is considered fully human in source, so maybe that’s a reason for its widespread use. Others, like Remicade, are hybrids.

A lot of the structure of biologics isn’t actually active. The active site, the part that binds to inflammatory factors, is a small part of the biologic molecule. Biosimilars aim to reproduce the active site, and the rest is less important.

Most biologics are antibodies to the messengers that cause inflammation, but some actually trick the messengers into becoming inactive. Enbrel, for example, acts as a decoy receptor to TNF-α. The TNF-α binds to Enbrel like it would normally bind to things while it’s doing its job, but since Enbrel isn’t actually the receptor, nothing happens.

There’s a lot that can be said about biologics, and there’s a lot that’s still yet to be understood. Is there something particular you want to know more about? Let me know, and I can cover it! For more information about biologics and how biosimilars are made, check out my post on biosimilars.

-Bri

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