The 5 Main Classes of Rheumatoid Arthritis Drugs

Rheumatoid arthritis (RA) is a chronic disease, and treatment can be complex. The five main classes of drugs used for treating RA are disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, biologics, nonsteroidal anti-inflammatories (NSAIDs), and analgesics. Each works a little differently and plays a different role in the management of RA. Some of these arthritis medications only relieve pain, some stop inflammation, and others target the disease process to prevent a flare-up of symptoms and prevent disease progression.

Aspirin tablets spilling from a bottle.

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RA treatment typically involves one or more of these medications to manage different aspects of the disease. Your healthcare provider will consider your medical history, current symptoms, and your disease progression in determining the right type of arthritis treatment for you.

DMARDs

Disease-modifying anti-rheumatic drugs (DMARDs) are slow-acting medications that work behind the scenes to hamper the progression of rheumatoid arthritis and reduce the risk of permanent joint damage.

DMARDs are the first-line treatment recommended for rheumatoid arthritis.

The most commonly prescribed DMARD is methotrexate (sold under the brand names Rheumatrex and Trexall). Otrexup and Rasuvo are both brands of single-dose injectable form of methotrexate

Other DMARDs include: 

Small-molecule DMARDs, also known as targeted synthetic DMARDs, including JAK inhibitors, are among the newer options in this drug class. Xeljanz (tofacitinib) is one of these. It works by inhibiting the JAK pathway inside cells, which plays a significant role in inflammation associated with rheumatoid arthritis.

DMARDs are taken on a long-term basis and can take weeks or even months to become fully effective.

Side Effects

When you're taking DMARDs, your healthcare provider will order periodic blood tests to monitor your kidney function, liver enzymes, cell counts, and inflammatory markers, all of which can be potentially affected by these drugs.

Side effects of DMARDs include upset stomach, nausea, diarrhea, hair loss, mouth sores, rash or serious skin reactions, and problems with the liver, kidneys, or lungs.

JAK inhibitors specifically have been linked with an increased risk of heart-related events, like a heart attack or stroke, in addition to cancer, blood clots, and death.

Corticosteroids

Corticosteroids, also called glucocorticoids, are synthetic drugs that mimic the effects of cortisol—a hormone naturally produced by the adrenal gland that affects several functions in the body, including the immune system. Cortisol has the ability to quickly control inflammation by decreasing levels of prostaglandins and inflammatory cytokines.

Healthcare providers often prescribe corticosteroids for fast, temporary relief of RA symptoms while waiting for DMARDs to take effect at the start of treatment or during a painful flare-up. Current American College of Rheumatology guidelines state steroids should be used for less than 3 months, at the minimal effective dose, in the treatment of RA.

Corticosteroids can be taken orally (tablet, capsule or syrup form); applied topically (cream, ointment); or injected into the joint (intra-articular), a muscle, or a vein (intravenously).

Corticosteroids commonly prescribed to treat rheumatoid arthritis include:

If your healthcare provider prescribes a corticosteroid for you, it's important to take it exactly as directed.

Side Effects

Despite their benefits, corticosteroids have the potential for undesirable side effects, such as infection, bone mineral density loss, increased appetite, weight gain, fluid retention, and high blood pressure—especially if they're taken for a long period of time or at a high dose.

Biologics

Biologics, so named because they are genetically engineered from living organisms, are a newer class of DMARDs. Biologics target specific inflammatory cells, cellular interactions, and cytokines that cause RA-related tissue damage. In doing so, biologics help reduce arthritis symptoms and slow disease progression.

Biologics are prescribed as add-on therapy if treatment with methotrexate or other DMARDs fails to relieve symptoms and influence disease progression.

Four main types of biologics are used to target different autoimmune reactions:

TNFIs are the most commonly prescribed class of biologics. Recommended as a second-line treatment when methotrexate and other DMARDs fail to control disease activity, they target an inflammation-causing substance called tumor necrosis factor (TNF).

In people with RA and other rheumatic conditions, high TNF levels contribute to inflammation and disease progression.TFNIs work by blocking TNF, therefore preventing inflammation in the joints.

Most biologics are self-injectable, but some are given intravenously in a hospital or outpatient center. 

Biologics cost more to produce and are more expensive than older DMARDs. Most health insurance companies require pre-approval paperwork from your healthcare provider detailing medical necessity prior to covering biologics.

Side Effects

Biologic therapies suppress the immune system and can make you more vulnerable to infections such as a cold, upper respiratory tract infection, sinus infection, sore throat, bronchitis, or urinary tract infection. Some increase the risk of non-melanoma skin cancer, and specifically TNF inhibitors can lead to rare neurologic complications (demyelinating disorders, like MS).

Other side effects include headache, nausea, and injection-site reactions.

NSAIDs

NSAIDs are a group of drugs primarily prescribed to reduce inflammation, pain, and fever, NSAIDs are commonly used to treat RA symptoms.

NSAIDs work by preventing an enzyme called cyclooxygenase (COX) from making prostaglandins, which are hormone-like chemicals involved in inflammation. COX-1 and COX-2 are the two types of these enzymes.

Traditional NSAIDs—such as aspirinnaproxen, and ibuprofen—block both COX-1 and COX-2 enzymes. Newer NSAIDs, such as Celebrex (celecoxib), block only COX-2; these drugs were developed because COX-1 is known to have a beneficial effect on protecting the stomach lining.

The newer NSAIDs and higher doses of older NSAIDs require a prescription. Many older medications are available over the counter (OTC) in reduced strength—for example, Advil (ibuprofen) and Aleve (naproxen).

While NSAIDs can be helpful for pain, they DO NOT change the course of RA or prevent joint destruction, which DMARDs do.

NSAIDs can be helpful for relieving pain and inflammation during a flare-up, but do have side effects if taken on a long-term basis. If you find yourself needing to take NSAIDs every day, talk to your healthcare provider to determine if changes to your medication regimen are necessary.

Analgesics

Analgesics are a class of drugs that includes non-narcotic pain relievers like Tylenol (acetaminophen) and opioid painkillers such as hydrocodone.

Analgesics work to relieve arthritis by changing the way the body senses pain. They can be effective for short-term pain relief during a flare-up but are not commonly recommended any longer. These pain medications do not change the course of RA or prevent joint destruction which DMARDs do.

Sold over the counter, acetaminophen is the most common analgesic. It is found as a standalone medication or in combination drugs like those formulated for colds, migraines, and period pain.

Side Effects

In large doses, acetaminophen can cause liver failure. Use caution to avoid mixing products containing acetaminophen and do not exceed 4,000 milligrams (mg) per day. Current guidelines set the daily limit at 3 gm/day from all sources.

Opioid analgesics such as oxycodone, codeine, and morphine are highly effective at reducing pain, but cause disorientation and can be fatal if taken in large doses.

Opioids are highly addictive and can quickly lead to physical dependence if taken regularly. They should be used sparingly, as directed, and only after other medications fail to bring relief.

Ultram (tramadol), a time-released opioid, is sometimes prescribed for moderate to severe RA pain as it is thought to have a lower risk of abuse than other narcotics. However, addiction is still a risk with this drug.

Vicodin, Lortab, and Norco are brand-name formulations of hydrocodone and acetaminophen. They should not be taken with Tylenol or a combination cold medicine.

Side effects of opioids include nausea, constipation, and trouble focusing or thinking clearly.

A Word From Verywell

Treating RA is important for maintaining your quality of life, slowing disease progression, and minimizing disability. Be sure to follow your healthcare provider's instructions and pay close attention to whether or not your symptoms are improving. It is not uncommon for an RA treatment regimen to change over time, so you may occasionally need some modifications in your therapeutic plan.

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