Biologics vs. DMARDs: Treating RA

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which the body’s immune system mistakenly attacks the lining of the joints (the synovium), causing pain and inflammation, which leads to joint damage over time. A common misconception is that RA only affects the joints in the hands, knees, and ankles; in some cases, other body organs such as the heart, eyes, skin, and lungs can also be damaged by RA. There is no cure for rheumatoid arthritis. However, early detection and treatment can slow down the progression of the disease. Your doctor’s decision on the treatment type will depend on the severity of the disease and how long you’ve been diagnosed with RA. Thanks to science and modern medicine, below are the four different treatment strategies for rheumatoid arthritis:

NSAIDs (nonsteroidal anti-inflammatory drugs)
Steroids
Conventional DMARDs
Biologic and targeted synthetic DMARDs

Please continue reading to learn some of the key differences between biologics vs. DMARDs or conventional DMARDs, to be specific. This will help you understand your options better when discussing the treatment of rheumatoid arthritis with your healthcare providers.

What are disease-modifying antirheumatic drugs (DMARDs)?

Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed to patients with rheumatoid arthritis. These drugs work by suppressing an overactive immune system and inflammatory response. They reduce inflammation and provide relief from joint pain. DMARDs also prevent joint damage. Besides treating rheumatoid arthritis, DMARDs are also used for other autoimmune conditions such as systemic lupus erythematosus, psoriatic arthritis, and ankylosing spondylitis.

It takes four to six weeks or longer for DMARDs to take effect. They do not provide immediate relief of RA symptoms. Doctors, therefore, often prescribe other medications for pain relief, such as nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or naproxen. Sometimes, the treatment strategy includes a steroid medicine like prednisone to provide faster relief. Compared to single drug therapy, combination therapy with DMARDs and other drugs can improve clinical outcomes and help to prevent joint damage.

It is important to keep in mind that DMARDs (disease-modifying antirheumatic drugs) are an umbrella term referring to all immunosuppressive and immunomodulatory agents, which are drugs that weaken or change the activity of the body’s immune system.

DMARDs are classified as biological or synthetic DMARDs; synthetic DMARDs are then further divided into two “subgroups,” which are conventional or targeted drugs. In other words, DMARDs is a term that refers to the following drug groups: conventional DMARDs, biologics, and targeted synthetic DMARDs.

A common myth is that biologics are not DMARDs or that conventional DMARDs and biologics are entirely unrelated. The fact is that both conventional DMARDs and biologics, along with targeted drugs, are all DMARDs; they all work to suppress the body’s immune system or inflammatory pathways--the differences are their mechanism of action and how they are made.

What are conventional DMARDs?

These drugs are also referred to as traditional DMARDs or conventional synthetic DMARDs.

Examples of the common conventional DMARDs used to treat RA include:

Sulfasalazine (Sulazine, Azulfidine)
Hydroxychloroquine (Plaquenil, Quineprox)
Methotrexate (Rasuvo, Otrexup, Trexall, Rheumatrex dose pack)
Azathioprine (Imuran, Azasan)
Leflunomide (Arava)

What are biologic drugs?

First available in the early 1990s, biologics are newer RA treatments that are prescribed when traditional DMARDs have not worked. While traditional DMARDs have a broader effect on the immune system, biologics are genetically engineered proteins that target specific parts of the immune system that drive inflammation.

Therefore, your doctor may prescribe a biologic treatment if previous methotrexate treatment (or some other conventional DMARD) has failed to provide relief of symptoms or slow disease progression.

Some biologic treatments are available as shots you can give yourself at home. Others must be given by intravenous (IV) infusion in a doctor’s office. Besides rheumatoid arthritis, biologic therapies are also used to treat other types of autoimmune or inflammatory rheumatic diseases.

Biologic therapy's disadvantages include the fact that these drugs weaken the body’s ability to fight against viruses and bacteria. People who take a biologic drug are more prone to infections.

Also, the effects of these drugs can be variable. One biologic agent may work well for some people but not for others. Biologic therapies may work well at first but then stop working. If a biologic drug works for you but then becomes ineffective, your doctor may suggest other biologic DMARDs.

Another thing to remember is that targeted biologic agents are more difficult to manufacture than conventional DMARDs. As a result, they are expensive, often costing thousands of dollars a month.

Examples of biologic DMARDs for RA include:

Tumor necrosis factor α inhibitors or anti-TNF biologics such as adalimumab (Humira), etanercept (Enbrel), certolizumab pegol (Cimzia), infliximab (Remicade), and golimumab (Simponi)
Interleukin-1 inhibitors like anakinra (Kineret)
Interleukin-6 inhibitors like sarilumab (Kevzara) and tocilizumab (Actemra)
B cell inhibitors like rituximab (Rituxan)
T cell inhibitors like abatacept (Orencia)

Lower-cost drugs called biosimilars are available for some of these original branded biologic DMARDs.

What other drugs are prescribed to patients with rheumatoid arthritis?

Another group of DMARDs, called kinase inhibitors, is also used to treat rheumatoid arthritis. Unlike biologics, kinase inhibitors are made using traditional drug-manufacturing techniques; therefore, they are also referred to as targeted synthetic DMARDs. These drugs are taken orally (by mouth) and work by blocking signaling pathways in the immune system.

Examples of kinase inhibitors for RA include:

Baricitinib (Olumiant)
Tofacitinib (Xeljanz)
Upadacitinib (Rinvoq)

What is the most successful treatment for severe rheumatoid arthritis?

Methotrexate is largely considered the most successful drug for treating rheumatoid arthritis. This medication, a traditional DMARD, can help achieve low disease activity and relieve symptoms like joint pain in most patients. However, treatment strategies for RA keep evolving and changing as newer drugs become available, which is excellent news since it provides clinicians and patients with different options for therapy depending on the disease severity and patients’ tolerability of the drug.

Until the 1980s, treatment strategies for rheumatoid arthritis were based on a pyramid approach. Doctors usually started treatment of early rheumatoid arthritis with a nonsteroidal anti-inflammatory drug or corticosteroid to provide relief from joint pain. They then added a disease-modifying anti-rheumatic drug (DMARD) in patients with more aggressive rheumatoid arthritis. If one DMARD failed, it was replaced by another one. In other words, treating rheumatoid arthritis was sequential, with one drug at a time.

Since the 1980s, low-dose methotrexate has been largely considered a safe and effective drug for rheumatoid arthritis. The approach has been to use DMARDs sooner rather than later. Clinical trials and clinical practice have shown that early and immediate treatment with DMARDs results in better clinical outcomes and delayed radiographic progression.

Are biologics more effective than DMARDs?

As mentioned above, biologics have a more precise treatment target than conventional DMARDs.

Most biologics start working faster than disease-modifying anti-rheumatic drugs. Some studies have shown biologics to result in less radiological deterioration (joint damage seen on X-rays) in patients with severe disease.

With that said, there is no strong evidence that biologic drugs have superior efficacy or result in better clinical and radiographic outcomes compared to traditional DMARDs.

Are biologics better than methotrexate for RA?

Biologics can work very well for some people who need more than the initial combination therapy of traditional DMARDs and/or NSAIDs and steroids. However, biologic DMARDs carry bigger risks of side effects, and they are more costly.

Nonetheless, experts recommend using biologic drugs sooner rather than later if they are needed. Again, it is worth remembering that every person reacts to different drugs differently. So, a biologic drug that works very well for one person may not work for someone else.

Do biologics have fewer side effects than traditional DMARDs?

Like most medications, biologics can cause side effects. Minor side effects of biologic drugs include nausea, abdominal pain, and injection site reactions like redness and itching. More serious side effects include infections like herpes zoster and tuberculosis, life-threatening allergic reactions, and lymphoma.

Remember, biologic agents interfere with the body’s ability to fight bacterial, viral, and fungal infections. These drugs cannot be used in people with serious infections or medical conditions like lymphoma or multiple sclerosis.

Also, you are required to take all the recommended vaccines before starting biologic drugs to reduce your risk of infections or adverse events. Your doctor will also test for tuberculosis (TB) before starting biologic DMARDs, especially anti-TNF biologics and kinase inhibitors.

How long can you stay on biologics?

There are mixed levels of evidence about the long-term safety and efficacy of biologic medications. However, for the most part, biologic disease-modifying antirheumatic drugs appear to be safe for long-term use.

Some people with RA become resistant to a biologic drug that initially worked well. This occurs because the body develops antibodies that counteract the beneficial effects of the drug.

If your symptoms of active disease don't improve after 3-4 months of taking a biologic drug or if the drug stops working, your doctor may recommend trying another one. There are more than a dozen biologics available today.

What is the safest biologic for arthritis?

The evidence suggests only minor differences in the comparative effectiveness and side effects associated with the different biologic agents for rheumatoid arthritis. There is some evidence, however, that Orencia and Kineret have the lowest risk of causing serious side effects.

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