Types of Rheumatoid Arthritis Medications

Drugs attack rheumatoid arthritis and its symptoms from various angles; some slow down the progression of the disease itself, while others target symptoms by reducing inflammation.

Rheumatoid arthritis (RA) medications are drugs that alleviate the symptoms of rheumatoid arthritis and slow down or halt its progression. Rheumatoid arthritis medications cannot cure rheumatoid arthritis, but early treatment greatly improves the chances of remission from the disease for significant periods. 

Drugs attack RA and its symptoms from various angles; some aim to slow down the progression of the disease itself, while others target symptoms by reducing inflammation or deadening pain.

The types of medications prescribed for rheumatoid arthritis include:

• Disease-modifying antirheumatic drugs (DMARDs) include:
  • Nonbiologic DMARDs
  • Biologic DMARDs
• Analgesics (painkillers)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids

Rheumatoid arthritis is a progressive inflammatory autoimmune disease that affects connective tissue known as synovium which lines and lubricates joints. Autoimmune diseases are conditions in which an abnormal immune system mistakenly attacks the body’s own tissues.

The immune system produces proteins known as cytokines and chemokines, which cause inflammation and thickening of the synovium and subsequent erosion of cartilage and bone in the joints. Rheumatoid arthritis causes swelling, stiffness, and pain in the joints, and joint deformity and organ dysfunctions in later stages.

RA is a systemic disease that initially affects the smaller joints such as fingers and toes, progressing to larger joints, and can eventually affect other organs such as eyes, skin, heart, lungs, and kidneys.

The exact cause of rheumatoid arthritis is not known, but genetic predisposition appears to play a primary role in its development. In juvenile rheumatoid arthritis, which starts before the age of 16 years, multiple genes are involved.

Other factors that are believed to trigger RA include:

• Infections: Reports of flulike disorders before the start of RA suggests a possible involvement of viruses like Epstein-Barr virus and rubella virus. Bacterial material and antibodies to bacteria such as Porphyromonas gingivalis which causes gum infection has been found in the synovial fluid of RA patients.
• Hormonal factors: The fact that RA is more prevalent in women than in men, among other characteristics, suggests hormonal involvement in the disease. For example, there is usually an improvement in women's RA symptoms during pregnancy and with the use of oral contraceptives -- both of which lead to changes in female sex hormone levels. 
• Immunologic factors: Abnormal functioning of various immune cells such as T cells, T helper 1 CD4 cells, and B cells result in the release of both pro-inflammatory and anti-inflammatory cytokines resulting in persistent inflammation.
• Environmental factors: Smoking, silica inhalation, gum disease and parasitic or bacterial infection in the gastrointestinal tract may be risk factors for RA.

It is essential to start treatment immediately upon diagnosis of rheumatoid arthritis. Chronic inflammation from rheumatoid arthritis can permanently damage joints and cause deformity over time, in addition to affecting several other organs in the body.

The types of medications prescribed for rheumatoid arthritis include:

• Disease-modifying antirheumatic drugs (DMARDs) include:
  • Nonbiologic DMARDs
  • Biologic DMARDs
• Analgesics (painkillers)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids

DMARDs are the primary medications that target rheumatoid arthritis and modify its course. All other medications are adjunct therapy to treat pain and inflammation from the disease.

DMARDs

Disease-modifying antirheumatic drugs constitute the primary treatment for rheumatoid arthritis. Early treatment with DMARDs can slow down or halt the progression of RA and reduce the risk of permanent, disabling damage to the joints. Each DMARD works in a unique way at the cellular level to prevent the immune system from promoting inflammation.

DMARD therapy takes up to six months to be fully effective. DMARDs work on specific types of immune cells and the cytokines they release. DMARDS are immunosuppressive, and long-term use can result in immune deficiency and a higher risk for infections.

Regular check-ups while on DMARD therapy is important, because continued use of DMARD medications can affect organs such as the eyes, liver, kidneys, or lungs. Switching to a different type of DMARD or a combination of DMARDs might be a more effective option for some people.

Nonbiologic DMARDs

Nonbiologic DMARDs are synthetic proteins produced in the laboratory, which slow down RA by suppressing immune activity. Common nonbiologic DMARDs include:

• Methotrexate (Trexall, Otrexup)
• Azathioprine (Imuran)
• Auranofin (Ridaura)
• Chloroquine phosphate
• Cyclophosphamide (Cytoxan)
• Cyclosporine (Neoral)
• Hydroxychloroquine (Plaquenil)
• Leflunomide (Arava)
• Minocycline hydrochloride (Minocin)
• Mycophenolate mofetil (CellCept)
• Penicillamine (Cuprimine)
• Sulfasalazine (Azulfidine)

JAK inhibitors

Janus kinase (JAK) inhibitors are synthetic small molecule drugs that block the activity of enzymes known as Janus kinases and their signaling pathways. Janus kinases stimulate immune cells to produce pro-inflammatory cytokines. JAK inhibitors used for RA treatment include:

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

Biologic DMARDs

Biologic DMARDs are proteins known as monoclonal antibodies that are genetically engineered in a laboratory. Biologics are more difficult to produce, more expensive, and used as second-line treatment if nonbiologic drugs like methotrexate are not sufficiently effective.

Biologic DMARDs may also be used in combination with a nonbiologic DMARD, typically methotrexate, when nonbiologic, single-drug therapy is not effective. Two types of biologic DMARDs are used for treating RA:

TNF inhibitors

TNF inhibitors block the activity of tumor necrosis factor (TNF), a major cytokine produced by immune cells such as macrophages and killer T cells. TNF regulates the activity of immune cells and plays an important role during acute inflammation. TNF inhibitors used in RA treatment include:

• Etanercept (Enbrel)
• Etanercept-szzs (Erelzi)
• Infliximab (Remicade)
• Infliximab-abda (Renflexis)
• Infliximab-dyyb (Inflectra)
• Adalimumab (Humira)
• Adalimumab-atto (Amjevita)
• Certolizumab pegol (Cimzia)
• Golimumab (Simponi, Simponi Aria)

Non-TNF agents

Non-TNF agents are monoclonal antibodies that work by inhibiting the activity of other cytokines such as interleukins, which are involved in the inflammatory process. Non-TNF agents are typically used when a patient does not respond well to TNF inhibitors. Non-TNF agents used for RA include the following:

• Abatacept (Orencia)
• Anakinra (Kineret)
• Rituximab (Rituxan)
• Rituximab-abbs (Truxima)
• Rituximab-pvvr (Ruxience)
• Tocilizumab (Actemra)
• Sarilumab (Kevzara)
• Experimental DMARD therapies

Rheumatoid arthritis continues to be a chronic disease and is active in many people who only partially respond to DMARD or sometimes not at all. Scientists continue to search for new medications targeting specific immune responses.

Some of the medications currently in clinical trials for RA treatment include the following:

• Belimumab
• Ofatumumab
• Ocrelizumab
• Fostamatinib

Analgesics relieve pain from rheumatoid arthritis, but they have no effect on swelling or joint damage. Moderate pain can be treated with non-opioid drugs but opioids may be more effective for severe pain. Opioids are the most potent analgesics, but carry a high risk for addiction.

Analgesics used for RA include:

• Non-opioid analgesics:
  • Acetaminophen (Tylenol, Feverall)
  • Tramadol hydrochloride (Ultram)
  • Though not technically an opioid, tramadol works on the same receptors in the brain and carries an addiction risk.
• Opioids
  • Fentanyl (Duragesic)
  • Hydrocodone bitartrate (Hysingla ER, Zohydro ER)
  • Hydromorphone hydrochloride (Dilaudid)
  • Meperidine hydrochloride (Demerol)
  • Methadone hydrochloride
  • Morphine sulfate (MS Contin)
  • Oxycodone hydrochloride (Oxycontin)
  • Oxymorphone hydrochloride
  • Tapentadol hydrochloride (Nucynta)
• Combination opioid drugs
  • Acetaminophen/codeine (Tylenol 3, Tylenol 4)
  • Acetaminophen/hydrocodone (Norco)
  • Acetaminophen/dihydrocodeine/caffeine
  • Ibuprofen/hydrocodone
  • Acetaminophen/oxycodone (Percocet, Roxicet)
  • Aspirin/oxycodone (Percodan)

Topical pain relief

The following over-the-counter analgesic creams and pain patches may provide some pain relief:

• Methyl salicylate (Salonpas)
• Capsaicin (Zostrix cream, Qutenza pain patch)

Non-steroidal anti-inflammatory drugs reduce swelling, inflammation, and pain by blocking the production of inflammatory chemicals. These drugs do not prevent the progression of the disease or joint damage. Anti-inflammatory drugs used for RA include:

• Aspirin
• Celecoxib (Celebrex)
• Diclofenac sodium (Voltaren)
• Ibuprofen (Advil, Motrin)
• Indomethacin (Indocin)
• Ketoprofen
• Nabumetone
• Naproxen sodium (Naprosyn, Aleve, Anaprox DS)
• Oxaprozin (Daypro)
• Piroxicam (Feldene)
• Salsalate
• Sulindac
• Tolmetin sodium

Corticosteroids are more potent anti-inflammatory drugs than NSAIDs, but long-term use can cause severe adverse effects that include bone thinning and immunosuppression. Corticosteroids are used to kill pain as a treatment “bridge” during the time DMARDs take to be effective. Doctors also administer corticosteroids for immediate relief during flares of RA.

Corticosteroids used as an adjunct therapy for RA include:

• Prednisone
• Prednisolone (Prelone)
• Methylprednisolone (Medrol, Depo-Medrol, Solu-Medrol)
• Cortisone acetate
• Dexamethasone
• Hydrocortisone (Cortef)
• Betamethasone (Celestone)
• Fludrocortisone acetate
• Triamcinolone (Kenalog, Aristospan)

Some natural products may be anti-inflammatory and help in reducing inflammation, though there is insufficient evidence for this. Natural remedies that have possible benefits for pain and inflammation include:

• Omega-3 fatty acids
• Gamma linoleic acid
• Herbal preparations with ginger, white willow, and devil’s claw

Discuss with your doctor the use of remedies before using. 

Doctors first treated rheumatoid arthritis with NSAIDs and progressed to more potent drugs only when signs of joint damage started to appear.

Current knowledge suggests that aggressive treatment of rheumatoid arthritis with DMARDs in the early stages, along with NSAIDs and corticosteroids as needed, is the best approach. Methotrexate is the most popular choice of DMARD therapy.

The latest treatment for rheumatoid arthritis is the Janus kinase inhibitor (JAK) class of DMARDs. The FDA approved the first JAK inhibitor, tofacitinib, in November 2012, and the two other JAK inhibitors baricitinib and upadacitinib in 2018 and 2019, respectively.

Additional information

Warning: The American College of Rheumatology (ACR) recommends that before undergoing DMARD therapy, RA patients should get vaccinations for influenza, pneumonia, hepatitis, human papillomavirus, and herpes zoster virus because DMARD medications suppress immunity.

• Please visit our medication section of each drug within its class for more detailed information.
• If your prescription medication isn’t on this list, remember to look on MedicineNet.com for drug information or discuss it with your healthcare provider and pharmacist.
• It is important to discuss all the drugs you take with your doctor and understand their effects, possible side effects, and interaction with each other.
• Never stop taking your medication and never change your dose or frequency without consulting with your doctor.