Biologics for RA: The Risks and Benefits

Medically Reviewed by Neha Pathak, MD on January 20, 2022
5 min read


There was a time, not very long ago, when a diagnosis of rheumatoid arthritis guaranteed a life of pain and disability. While there still isn’t a cure, the outlook is much brighter.

“[Things] have definitely changed for the better,” says Beth Jonas, MD, a rheumatologist with the University of North Carolina’s Thurston Arthritis Research Center.

Medications called biologic response modifiers -- or biologics -- have turned the tables. The use and ongoing development of these drugs have given people with RA -- and their doctors -- hope.

“It is very unusual now, in the year 2017, for me to have [someone] that I just can’t treat,” Jonas says. “I can’t tell you how great that feels. It’s a world of difference from just 20 years ago, before biologics.”

Treatment for RA has come a long way since the days of bloodletting and leeching -- the gold standards of care many decades ago.

In the 1930s, doctors used actual gold to treat patients with RA. These injections were part of a group of drugs called disease-modifying anti-rheumatic drugs. You probably know them as DMARDs.

Gold compounds aren’t used much these days. Since the 1990s, the cornerstone of RA treatment plans has been a DMARD called methotrexate. Instead of directly treating pain and symptoms, they go after the underlying disease. By doing that, Jonas says, folks have less inflammation, pain, and damage.

“Methotrexate was a real game changer. It got people up and moving,” she says.

Some, she adds, not all. Jonas says about half of folks with RA got going.

Over time, researchers got a better grasp of how the disease works in your body. That led to the discovery of new parts of the body to focus on, and the development of biologics.

These biologic DMARDs are genetically engineered proteins made from human genes. They’re designed to target parts of your immune system that drive inflammation.

They do so with a sniper’s aim.

Guy Eakin, senior vice president for scientific strategy at the Arthritis Foundation in Atlanta, says that’s a big change from non-biologic drugs like methotrexate, which fight RA with more of a sledgehammer-like approach.

“The greatest advantage of using biologics to treat rheumatoid arthritis is that they can be exquisitely targeted to a specific player in our body’s immune system,” he says.

One of the key issues with traditional, oral DMARDs like methotrexate is they take weeks to months to work. Not so with biologics.

“Meanwhile, biologics gave us a tool that was potent and fast, and their ability to prevent joint damage is better,” Jonas says. “What we have learned over time is that a combination of biologics and methotrexate works better than either one alone.”


Etanercept (Enbrel) was the first biologic to be approved by the FDA. Since that approval in 1998, there are now at least eight more biologics for RA.

The first ones were known as anti-TNF agents. In other words, they block a substance called tumor necrosis factor. TNF causes joint inflammation and destruction.

When your doctor decides to go the biologics route, you’ll usually get TNF inhibitors first.

But what if your RA has nothing to do with TNF?

“Predicting the right drug can be tricky,” Jonas says. “Most of our first choices are TNF inhibitors, but we might have to switch to biologics with different mechanisms.”

Other biologics used to treat RA include:

Abatacept: Blocks communication between inflammatory T cells (those are a type of white blood cell)

Anakinra: Hampers the protein interleukin-1, a major culprit in inflammation

Baricitinib: A JAK inhibitor that tamps down inflammation

Rituximab: First used to fight non-Hodgkin’s lymphoma, this destroys white blood cells that help cause inflammation.

Sarilumab: An antibody that blocks the interleukin-6 receptor, known to cause inflammation

Tocilizumab: Targets interleukin-6, an immune system protein that fuels inflammation

Tofacitinib is almost in a class by itself. You can take it by mouth. It inhibits enzymes that help cause inflammation.

When thinking about the biologic big picture, Eakin thinks of an adage from the "Spider-Man" movies: “With great power comes great responsibility,” he says.

“When we talk about RA, what we’re actually doing with biologics is turning off part of the immune system. Or, more broadly, we are manipulating the immune system.”

The best strategy is to talk with your doctor about the different side effects associated with each drug.

“The biggest risk with this whole class of biologic drugs is infection,” Jonas says. That’s because of the changes the drugs make to your immune system.

There have been other concerns. The FDA issued a warning in 2009 that there is an increased chance of cancer in kids and teens who use biologics to treat juvenile arthritis. But, Eakin notes, there’s also a risk from other drugs used to treat the same thing.

“When you look back at billing records from the last 15 years, you can see that the cancer risk is similar for kids taking biologics versus those who aren’t,” he says.


The biggest hurdle with biologics is the price.

“The expense is crazy, the cost is high,” Jonas says.

Some relief may come with a new line of drugs called biosimilars, which will be entering the marketplace soon.

According to the Arthritis Foundation, biosimilars “have the potential to provide safe and effective treatment to people with arthritis at a significantly lower cost than name-brand biologic medications.”

But make no mistake. Biosimilars are definitely not generic versions of biologics.

Generic drugs are copies of brand-name drugs, with the same active ingredient, the same everything: dosage, safety, strength, etc.

Biosimilars are just what the name implies. They’re similar to the biologic they’re based on, but, because they’re made from living organisms, there are acceptable differences. In terms of safety, potency, and purity, they have no meaningful clinical differences from the biologic.

“Biosimilars are different from biologics in very nuanced ways,” Eakin says. “But, by and large, they are considered identical to one another.”

The estimated cost reduction for a biosimilar is 15% to 20%.

Whatever the cost, the basic rule when treating RA with biologics is, the earlier, the better.

“We know that the longer you have RA, the more likely you’ll have joint damage, so the key is to get started before that happens,” Jonas says. “And when the timing works out, the results are sort of amazing.”