Antirheumatics: Uses, common brands, and safety info

Aches and pains in our bones, joints, and muscles may be caused by everyday wear and tear, overuse, or even aging. Chronic pain in bones, joints, or muscles may be due to a more serious inflammatory disorder such as osteoarthritis or rheumatoid arthritis or, in children, juvenile idiopathic arthritis. These chronic pains are classified as rheumatic diseases and often require drug treatment to help not only with painful symptoms but also to prevent disease progression.

Medicines such as corticosteroids (e.g., prednisone) and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (e.g., Motrin IB) or naproxen (e.g., Aleve), can help reduce pain and inflammation but do not treat the underlying cause, i.e., do not stop the progression of chronic inflammatory diseases such as rheumatoid arthritis. Antirheumatic drugs, also known as disease-modifying antirheumatic drugs or DMARDs, are a category of drugs that provide relief from symptoms but also slow down the progression of inflammatory disease. 

The following table lists commonly used antirheumatic drugs followed by information on how they work, what conditions they treat, safety, and cost.

Other antirheumatics

• CellCept (mycophenolate mofetil)

• Orencia (abatacept)

• Benlysta (belimumab)

• Taltz (ixekizumab)

• Rituxan (rituximab)

• Kevzara (sarilumab)

• Cosentyx (secukinumab)

• Actemra (tocilizumab)

• Stelara (ustekinumab)

• Cimzia (certolizumab pegol)

• Olumiant (baricitinib)

• Kineret (anakinra)

What are antirheumatics?

Antirheumatics are any drugs used in the treatment of autoimmune diseases marked by inflammation and pain in the joints, muscles, or fibrous tissues (such as ligaments and tendons). Antirheumatics act as immunosuppressives and can reduce or prevent joint arthritis damage associated with inflammatory disorders and reduce pain and stiffness.

How do antirheumatics work?

Conventional DMARDs

Although the exact mode of action for the conventional DMARDs is unknown, it is thought that they decrease tissue damage caused by rheumatic diseases by suppressing toxic compounds or their metabolites that damage tissues. 

Biologic DMARDs

Biologic DMARDs stop or block particular cells in the immune system from triggering inflammation. Some biological therapies are called Tumor Necrosis Factor blockers or anti-TNFs. They target a protein that increases inflammation when excess amounts are present in the blood or joints. Other biological DMARDs target different proteins that cause inflammation.

Targeted synthetic DMARDs

Targeted synthetic DMARDs were developed specifically to target a key step in the initiation of the inflammatory response. These drugs are known as Janus kinase inhibitors (JAK) and they block the action of the Janus kinase enzyme which leads to the inflammation that causes the symptoms and damage of rheumatic diseases.

What are antirheumatics used for?

Antirheumatics are a group of medications commonly used in people with autoimmune inflammatory conditions that cause the body’s immune system to attack joints, bones, tendons, ligaments, and even some organs. Some antirheumatics have antimalarial agents and can be used in the treatment of Malaria. Antirheumatics are also used in treating other conditions such as cancer and for the prevention of tissue rejection following transplant surgery. Following is a list of common rheumatic disease conditions for which antirheumatics are often prescribed:

• Rheumatoid arthritis

• Psoriatic arthritis

• Juvenile idiopathic arthritis

• Ankylosing spondylitis 

• Systemic lupus erythematosus (SLE)

• Crohn’s disease

Types of antirheumatics 

There are three different categories of antirheumatics and they have different therapeutic effects and mechanisms of action.  

Conventional DMARDs

Conventional synthetic DMARDs, also known as “traditional” DMARDs, have long been considered first-line therapy for inflammatory conditions such as rheumatoid arthritis. This group of drugs typically can take several weeks to work, so it’s important to give them time if they don’t seem to help at first. If the rheumatic condition doesn’t respond to one of these drugs, it is common for the healthcare professional to suggest an alternative conventional DMARD for the treatment of rheumatoid arthritis. They may be prescribed as a single treatment or as combination therapy with other conventional or biologic DMARDs. This category includes the following:

• Imuran (azathioprine)

• Neoral (cyclosporine)

• Cytoxan (cyclophosphamide)

• Plaquenil (hydroxychloroquine)

• Arava (leflunomide) 

• Methotrexate

• Azulfidine (sulfasalazine)

• Azulfidine EN-tabs (sulfasalazine delayed-release)

• Cuprimine (penicillamine) 

Biologic DMARDs

Biological DMARDs are a relatively newer group of medicines, many developed using monoclonal antibody technology, that normally take effect more rapidly than conventional DMARDs. The biological DMARDs are typically given to those who did not respond well to other antirheumatic therapies and they may be given alone or in combination with a conventional DMARD. This category includes the following:

• Orencia (abatacept)

• Benlysta (belimumab)

• Ilaris (canakinumab)

• Taltz (ixekizumab)

• Rituxan (rituximab)

• Kevzara (sarilumab)

• Cosentyx (secukinumab)

• Actemra (tocilizumab)

• Stelara (ustekinumab)

• Tumor necrosis factor (TNF) inhibitors:

  • Humira (adalimumab) 

  • Cimzia (certolizumab pegol)

  • Enbrel (etanercept) 

  • Simponi (golimumab)

  • Remicade (infliximab) 

Targeted synthetic DMARDs

In contrast to conventional DMARDs that have more widespread actions within the body to treat inflammatory diseases, targeted synthetic DMARDs act on one specific step in the body’s inflammatory response pathway. These are the newest antirheumatic drugs available and include the following:

• Olumiant (baricitinib)

• Xeljanz (tofacitinib)

Who can take antirheumatics?

Adults

All three categories of antirheumatics are approved by the U.S. Food and Drug Administration (FDA) for a variety of rheumatic diseases for adult men and women. Because there are a number of treatment options for rheumatic diseases, healthcare professionals must tailor a drug regimen appropriate for each person’s individual situation.  Treatment choices are typically determined by the severity of the condition, the effectiveness of specific therapies, and the emergence of any side effects. Treatment choices may also be impacted by the person’s other health conditions.

Children

The FDA has approved the following antirheumatics for use in pediatric patients to treat juvenile idiopathic arthritis:

• Methotrexate: 2 years of age and older

• Humira (adalimumab): 4 years of age and older

• Orencia (abatacept): 6 years of age and older

• Enbrel (etanercept): 2 years of age and older

• Actemra (tocilizumab): 2 years of age and older

• Ilaris (canakinumab): 4 years of age and older

The efficacy and safety of the other antirheumatics have either not been demonstrated or have not been fully evaluated in randomized controlled trials and their use is not recommended in children or adolescents to treat juvenile idiopathic arthritis.

Seniors

In general, in clinical studies of antirheumatics, no overall differences in safety or effectiveness were seen between older patients and younger patients however the numbers of trial participants over age 65 were often too low to rule out differences. The frequency of serious infection in patients over age 65 was higher than for those under age 65 therefore caution should be used when treating the elderly. Also, older adults often have additional medical issues so less aggressive treatment regimens are typically considered the best therapeutic choice.

Women who are pregnant or breastfeeding

In general, there have been no adequate and well-controlled studies on the use of antirheumatics in pregnant women and they should not be administered unless the potential benefit justifies the potential risk to the fetus. In addition: 

• Arava (leflunomide), Cuprimine (penicillamine), Imuran (azathioprine), and CellCept (mycophenolate mofetil) are contraindicated in pregnant women or women of childbearing potential not using a reliable contraceptive.

• Methotrexate is contraindicated in women of childbearing potential. Pregnancy should be avoided if either the male or female partner is taking methotrexate (during and for a minimum of three months after therapy for male patients, and during and for at least one ovulatory cycle after therapy for female patients.)

It is not known whether antirheumatics are excreted in human milk therefore it is not recommended they be given to nursing women. Some antirheumatics, specifically methotrexate and Arava (leflunomide), are contraindicated in nursing mothers.

A woman’s healthcare provider is the best source of information when deciding to start or continue antirheumatics during pregnancy or while breastfeeding.

Are antirheumatics safe?

Several antirheumatics have an FDA-mandated “boxed warning,” also called a black box warning, highlighting major safety concerns: 

• Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens:

  • Humira (adalimumab)

  • Xeljanz (tofacitinib)

  • Remicade (infliximab)

  • Enbrel (etanercept)

  • Actemra (tocilizumab)

  • Kevzara (sarilumab)

  • Cimzia (certolizumab pegol)

  • Olumiant (baricitinib)

  • CellCept (mycophenolate mofetil)

  • Simponi (golimumab)

• Lymphoma and other malignancies, some fatal, have been reported:

  • Humira (adalimumab)

  • Enbrel (etanercept)

  • Cimzia (certolizumab pegol)

  • Olumiant (baricitinib)

  • Imuran (azathioprine)

  • Neoral (cyclosporine)

  • CellCept (mycophenolate mofetil)

  • Simponi (golimumab)

• Arava (leflunomide): toxicity leading to severe liver injury, including fatal liver failure, has been reported.

• Rituxan (rituximab): fatal infusion reactions within 24 hours, tumor lysis syndrome, severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML) resulting in death have been reported.

• Olumiant (baricitinib): thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, some fatal, have occurred in patients. 

Recalls

There are no current antirheumatics product recalls as of January 2022. 

Restrictions

Persons with known hypersensitivity or allergies to the ingredients of individual antirheumatics should not take them.

Individual antirheumatics have the following contraindications:

• Azulfidine (sulfasalazine) and Azulfidine EN-tabs (sulfasalazine delayed-release) are contraindicated in patients with intestinal or urinary obstruction

• Methotrexate is contraindicated in patients with chronic liver disease

• Remicade (infliximab) is contraindicated at doses greater than 5 mg/kg in patients with moderate to severe heart failure

• Cyclophosphamide is contraindicated in patients with urinary outflow obstruction

Are antirheumatics controlled substances?

No, antirheumatics are not controlled substances.

Common antirheumatic side effects

Side effects common to all antirheumatic drugs include:

• Gastrointestinal distress (nausea, abdominal pain, diarrhea)

• Rash/allergic reactions

• Increased incidence of common and sometimes serious infections

• Injection site reactions (for injectable drugs)

How much do antirheumatics cost?

The price of antirheumatics varies greatly between the conventional DMARDs, many of which are available as cheaper generic drugs, and the newer biologic DMARDs and targeted synthetic DMARDs. Cost may also depend on insurance coverage. The best way to find out how much you will pay is to contact your insurance or Medicare prescription plan for up-to-date coverage information. You can always use a free SingleCare card to save money on your antirheumatic prescription at participating pharmacies.