Picture a wheel. Now picture that wheel in continuous motion, rolling on and on.
Then the wheel stops.
Why does it stop? Well, logically, because something has stopped it.
The wheel is the inflammation in your body from rheumatoid arthritis (RA).
The thing that stopped it from rolling on, damaging your joints and causing pain in the process—what’s that?
That’s a biologic medication.
You’ve just read one of the ways that Victoria Ruffing, R.N., director of nursing and patient education at the Johns Hopkins Arthritis Center in Baltimore, explains how biologics target the abnormal immune response that leads to inflammation and RA. The immune system is complex, she says. Using a simple analogy can help people grasp what, exactly, these medications do. By thinking of inflammation as a wheel in motion, always present, you can better imagine how a biologic would stop that process in its tracks.
But this is just the very beginning. Here's what comes next in your biologics education.
What Are Biologics and How Do They Work?
They’re lab-made proteins that work like antibodies (your natural antibodies fight viruses and bacteria). Biologics also have specifc targets, but instead of germs they lock onto cytokines. These immune-system messengers are part of the chemical cascade that causes inflammation, says Daniel H. Solomon, M.D., professor of medicine in the division of rheumatology at Brigham and Women’s Hospital in Boston.
“If we block these messengers, we can dampen the inflammation that is a driving factor in the pain and disability caused by rheumatoid arthritis,” he explains.
Biologics aren’t just for RA—they’re used to treat many inflammatory conditions including psoriasis, psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease. They’re part of the disease-modifying antirheumatic drugs, or DMARDs, used in RA patients. The U.S. Food and Drug Administration (FDA) has approved eight biologics for RA. Each biologic is in a specific “class,” targeting a different cytokine. For the drugs to be most effective, you need to start taking them and not stop (as long as they're working well for you). So yes, you might have to take biologics for a long time.
“When I speak to patients who are newly diagnosed, I am optimistic about their prognosis,” Dr. Solomon says. "However, most patients will stay on treatments probably for the rest of their lives. Some patients will be able to stop, but that’s the minority,” he says
That’s why Michael George, M.D., a rheumatologist and assistant professor of rheumatology and epidemiology at Penn Medicine in Philadelphia, tells his patients to not look too far into the future. He encourages them to focus on today, paying attention to whether their biologic is working to keep their RA pain at bay right now—as much as they can, of course.
“It is impossible to predict what someone’s disease will be like in a few years or what new treatments may have come along. The search for a cure continues,” Dr. George says.
Dr. Solomon adds that we’re in a “period of rapid growth of biologic DMARDs” for RA. Always encouraging to hear.
How Will My Body (Likely) Respond to a Biologic?
Everyone is different, so everyone responds differently to biologics, on his or her own schedule. On average, it takes about four or more weeks for symptoms to decrease, Ruffing says.
You might not respond to the first biologic you try, and no tests yet exist to help doctors better determine which drug will work best with your RA, says Dr. George. “Sometimes it requires some trial and error to find the best treatment. Fortunately, even if the first biologic doesn’t work, patients will often have a response to a different biologic,” he explains. The good news is you have options.
Another thing to know: You can stop experiencing good symptom control with biologics—even after years using the drug. Sometimes your body develops its own antibodies against the drug, blocking its effects (some people develop an allergic-type reaction), or you may eventually need a higher dose to maintain improvement. Staff at Johns Hopkins Arthritis Center focus on the positive aspects of the medication working, while also following a patient’s progress at regular three-month visits, Ruffing says. They check how many joints are swollen and tender, monitoring for any trends in symptoms.
“We don’t say from the beginning, ‘This drug may eventually fail.’ I think we know intuitively that not everything is going to work for all people and it may not work for all time,” she says. “Yet we have people on these medications for 10, 15 years.”
So how will you know if it’s working? One of the first signs RA symptoms are easing in the patient population she sees: less fatigue. “They feel like they have a little more energy,” Ruffing says. “They just don’t feel like they’re dragging as much as they were. And then from there comes the calming down of the inflammation and the lessening of any pain or morning stiffness,” she says.
What’s the Goal of These Drugs?
Put simply: remission. And that’s defined as no disease activity, no noticeable signs and symptoms of RA, or minimal signs and symptoms. So you can have a few tender or swollen joints and the drugs are still considered effective.
When you hear “remission,” you might think of cancer remission, but it’s not exactly the same kind of remission, he says. Some cancer types have the possibility for a cure, but it’s likely a different story in RA.
“We continue to treat most RA patients [for life], so we recognize that most patients who get to remission will have another flare of rheumatoid arthritis if their medications are stopped,” Dr. Solomon notes.
Am I Candidate for Biologics?
You’re a candidate for a biologic if you have moderate-to-severe RA and have been on DMARDs, but your symptoms are not improving. RA patients often start treatment with methotrexate, an immunosuppressive medication. Doctors have been prescribing this pill for more than 30 years to RA patients, and it works for a large group of people as “monotherapy,” medical speak for just one treatment, according to Dr. Solomon. When it doesn’t, it can be combined with other DMARDs such as leflunomide and sulfasalazine. It can also be combined with biologics for improved results.
Methotrexate is the “cornerstone therapy” for RA because it’s typically the first drug given, has so many years of prescribing behind it to show safety and efficacy, and can be combined with other drugs, Dr. Solomon says.
“Patients who aren’t doing well on methotrexate monotherapy who don’t want to take additional pills on top of the methotrexate would be typical candidates for biologics,” he explains. “Combining several types of pills, so-called triple therapy, works about as well as a biologic.”
How Do I Take Biologics?
Usually, by infusion (which is given by IV) or injection under the skin, called a subcutaneous injection. These drugs currently can’t be given orally because their molecules are too large to cross the stomach or intestinal lining easily. And they’re typically given either only as an infusion or only as an injection after the initial first “loading dose,” (meaning the higher dose of a drug used at the start of treatment, before a lower maintenance dose is given).
Infusions can be done at infusion centers, some of which are affiliated with hospitals, as well as at home, with the help of a home-care nurse. If patients are nervous about having an IV medication on a regular basis (dosing can differ by patient and drug), Dr. George reassures them that infusions are quite safe: “Most patients have no problems at all with the infusion. Some patients may have an infusion reaction, such as flushing or palpitations, but if anything like this happens, the nurses at the infusion center will know how to treat this.”
Injections are typically done at home, with the first dose sometimes done at an office setting with a nurse instructing or assisting. Some drug companies send a nurse to your home to show you how to use the injectable.
“If [patients] are anxious about their first treatment, it might be a good idea to come into the office to have a nurse help with the first injection. After doing it once or twice, they will realize how easy this is to do,” says Dr. George.
Because these injections are given under the skin, they don’t go as deep as intramuscular injections, which require larger needles and can be more painful. They also are typically given with a pen injector, with retractable needles, meaning you don’t see the needle itself as you use it. You place the pen on your skin (commonly your thigh, stomach, arm, or leg), press the release button, wait the allotted time for the medication’s release, dispose of the injector in an FDA-cleared sharps disposal container, apply a bandage if needed, and you’re done.
Are There Side Effects?
Yes. Patients can experience side effects including (but not limited to) an increase in (often serious) infections, irritation at the injection site, headache, and nausea. In rare cases, some types of cancer, including lymphoma, have been reported, as well as heart issues in people with pre-existing heart conditions, and problems in the nervous system.
But in the 21 years since Enbrel came on the market, the side effect profile has been “remarkably safe,” Dr. Solomon says. Also, it should be noted: “There’s no medicine that we give in medical practice, including aspirin, that doesn’t have potential for side effects.”
“That doesn’t mean they’re safe in everyone,” he says of biologics. “But over the millions of patients that have received these drugs, the majority of patients tolerate them without difficulty.”
Ruffing teaches patients how to identify the signs of common infections, such as how a sinus infection or urinary tract infection feels and what an infected cut looks like, in case they experience one while on a biologic. She tells patients to call their doctor’s office if they suspect they have one of these infections.
People on biologics are often wary of infections, Dr. George says, but he tells them that the risk of having a serious infection related to biologics is actually low: “Based on what we know, if 100 people are treated with one of these medications for one year, approximately one additional person may have a serious infection—for example, pneumonia serious enough to require going to the hospital.”
And if biologics help reduce your prednisone dose or improve your disease activity, you could reduce your risk of infection too, Dr. George notes.
How Do I Get Biologics?
So: These drugs are live cells, rendering them expensive to make—synthetic chemical drugs, like the common over-the-counter meds we all know (think aspirin or acetaminophen), are far cheaper to produce.
As a result, biologics are pricy.
For example: One carton of Enbrel (or four SureClick autoinjectors) retails at the average price of $5,560.61. So if you take one injection a week, that’s about $1,390 for your weekly medication, or $198 a day.
Most private insurers cover these medications, often requiring prior authorization, including that the patient has tested negative for tuberculosis and Hepatitis B (if a patient has active disease, it can seriously worsen on biologics); been on a cheaper synthetic drug first like methotrexate, sulfasalazine, or hydroxychloroquine; and has moderate-to-severe RA, Ruffing says.
For your infusion, your center will typically have your medication, and a nurse will prep it; though sometimes patients have to provide their medication to their nurse, Dr. Solomon says.
But, typically, you don’t go to your local pharmacy to pick this medication up, Ruffing says. The prescription for an injectable usually goes through a specialty pharmacy and arrives by mail order, delivered by a package carrier like UPS or FedEx, in a Styrofoam cooler with ice packs, because it needs to stay refrigerated. It often comes in a 90-day supply, approved for one year before the insurance company will review, to ensure that the biologic is still working.
For patients on Medicare with no secondary insurance, receiving these expensive medications can be more difficult than for those privately insured, Ruffing says, sometimes requiring other means of funding, such as patient foundations.
“Most of the companies do have programs that are very generous in trying to help patients that are uninsured or underinsured. But even so, we have to spend a lot of time appealing and writing letters and unfortunately, all of that time that we spend on a patient trying to get access to a medication, none of that is reimbursable. It’s really quite a burden on us, and a burden on the patient,” she says.
What Else Should I Know?
Here are some final thoughts from those we spoke to about biologics for RA.
Dr. Solomon finds these drugs promising now and into the future.
“Most [RA] patients are going to find that, whether through non-biologic therapies, or biologic therapies, that there is a medicine that helps them. Not every patient is able to go into remission, but the vast majority of patients are able to get significant improvement in their symptoms and many, many patients get to low-disease activity or remission,” he says.
If patients are concerned about going on a medication that they might have to take forever, Dr. George tells them: “Most patients do very well on these medications without side effects,” he says.
And finally, Ruffing says that with careful monitoring and changes as-needed, RA patients can receive safe and effective treatment with biologics.
“We have a lot of confidence in the biologics,” she says. “We follow the guidelines from the American College of Rheumatology, and if we’re not seeing improvement within what we think is a reasonable amount of time, then we’re either switching or adding or making a change to somebody’s treatment plan to make sure we’re preventing any kind of destruction or loss of function that patients might have.”