Treatment & Management

of Rheumatoid Arthritis

Advances in our understanding of rheumatoid arthritis (RA) have led to earlier and more aggressive treatment of this condition. Several different types of RA drugs are available, and decisions about which drug or combination of drugs to use will depend on your particular situation. Your rheumatologist will work with you to develop an individualized treatment plan.

During treatment, make sure that all of your healthcare providers are informed about all of your medications. This includes prescription medications, over-the-counter medications, and dietary supplements. Some products may not be safe to combine with your RA medications.

The goals of therapy for RA are to control inflammation, decrease pain, maintain function, and prevent deformity with the fewest side effects. A therapeutic program will include non-drug and drug components.

Drug Therapies for Rheumatoid Arthritis

A wide variety of drug therapies are available for the treatment of RA.   The key to success is matching the degree of illness with the corresponding drug. Why not treat RA patients with all the drug categories? Each drug category has associated side effects and physicians want to limit those exposures to a minimum. Essentially, the goal is to  take the most appropriate number of medicines associated with the least number of side effects to achieve the best therapeutic response.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs, a class of drugs that includes aspirin, can decrease pain, fever, and inflammation. NSAIDs are anti-inflammatory and pain-relieving when given in larger doses long term. In RA, NSAIDs decrease joint stiffness and pain but are often inadequate by themselves to control disease symptoms and improve function.

NSAIDs, work by blocking an enzyme in the body named cyclooxygenase -2 (COX-2), COX -2 produces prostaglandins. Prostaglandins are associated with heat, swelling, and pain associated with tissue injury. In addition to blocking COX-2, most NSAIDs block cyclooxygenase -1 (COX-1). The prostaglandins made by COX-1 help preserve the stomach, lining, regulate kidney function, and maintain normal blood pressure. Nonselective NSAIDS BLOCK BOTH cox-1 and 2.  By blocking COX1 and 2 the risk of gastrointestinal bleeding and esophageal reflux are increased.  A COX-2 inhibitor, Celecoxib may inhibit COX-2 without affecting COX-1 enzyme decreasing the risk of gastrointestinal toxicities.

NSAIDs fall into a number of different chemical groups. An individual may respond to one and not anther. Any single NSAID may help about 66% of the people who try it. Some individuals have to try 3 or more NSAIDs before finding the one that works.

NSAIDs can be taken by mouth, or used topically as a gel or patch. The downside of topical use is that they may need frequent application up to 4 times a day to be effective. Even though the dose is lower, topical therapies are associated with toxicities similar to the oral form of the NSAID.

Disease-Modifying Agents (DMARDs)

DMARDs are drugs that work more slowly than NSAIDs but have the capability of modifying the progression of disease. These drugs have greater benefit in rheumatoid arthritis. DMARDs do not have a beneficial effect on spinal disease. There are two categories of DMARDs: biologic (created to be similar to proteins found in the body) and non biologic.

Biologic DMARDS

Anti-Tumor Necrosis Factor Inhibitors (TNFi)

Cell messenger or cytokines, are released by cells to initiate a variety of functions. An inflammatory cytokine, TNF is associated with the clinical manifestations of AS. TNF is associated with fatigue, joint swelling, stiffness, and pain. A decrease in the production of TNF, or removal from the blood stream can result in a decrease in disease-associated complaints. However, the total removal of TNF can be associated with an increased risk of infection. The goal of therapy is to obtain a physiologic level of TNF. There are a number of ANTI-TNF therapies available for the treatment of AS including:

  • Enbrel (entarnercept) is a soluble receptor for TNF injected weekly.
  • Humira (adalimumab) is a fully human anti-TNF monoclonal antibody administered by injection every 2 weeks.
  • Simponi (golimumab) is a fully human anti-TNF monoclonal antibody that is injected monthly.
  • Cimzia (certolizumab) is an anti-TNF partial antibody connected to polyethylene gycol that prolongs the effect of the antibody that is injected every 4 weeks
  • Remicade (infliximab) is a monoclonal directed against TNF that is administered intravenously every 4 to 8 weeks.

The effectiveness of the TNF therapies shows no benefit of one agent compared to another. The use of specific agents in individuals is based on personal preference related to injections versus infusion and frequency of dosing.

Side effects associated with the use of TNF inhibitors include the activation of latent tuberculosis and increased risk of viral and bacterial infections. If infections occur, the infection is treated and the TNF therapy stopped until the infection is resolved. An increased risk of malignancy has been reported. However the degree of this increase which is reported to be small and is undergoing active evaluation.

The use of specific DMARDs in individuals is mainly based on personal preference related to injections versus infusion and frequency of dosing.

Side effects associated with the use of TNF inhibitors include the activation of latent tuberculosis and increased risk of viral and bacterial infections. If infections occur, the infection is treated and the TNF therapy stopped until the infection is resolved.  A small increased risk of certain cancers has also been reported and is undergoing active evaluation.

Selective T-cell Costimulator Inhibitor

  • Orencia® (abatacept) Activation of lymphocytes requires a sequence of signals. Immune response that results in RA is diminished if these secondary signals are blocked.  Orencia® is a fusion protein that inhibits antigen-presenting cells from delivering co-stimulatory signals that activate T cells.  Orencia® is administered by monthly infusions or subcutaneous injections.

Interleukin -6 Inhibitors

  • Actemra® (Tocolizumab) is a humanized monoclonal antibody directed against Interleukin -6 (IL-6), receptors, blocking the effect of IL-6, a cytokine that mediates a portion of the destructive immune response in RA. Inhibition of IL-6 is associated with decreased inflammatory complaints and joint destruction in RA.  Actemra® is administered by monthly infusions or subcutaneous injections. Infection and rarely, bowel perforation occurs.
  • Kevzara (Sarilumab) is a fully human monoclonal antibody directed against IL-6, both soluble and membrane bound. Kevzara is administered as an injection every 2 weeks. Toxicities include infections and lowering of blood counts.

Janus Kinase Inhibitors

  • Xeljanz® (tofacitinib) Janus kinases (Jak) are a series of enzymes that activate lymphocytes resulting in inflammatory responses. Xeljanz® is a small molecule that inhibits Jak 3 and, to a lesser degree, Jak2.  Xeljanz® is an orally administered medication taken on a daily basis.

Rituxan® (rituximab)

B-lymphocytes are components of the immune system contributing to the destructive changes of RA. Rituxan® is an antibody combining mouse and human components. The antibody is directed against the CD 20 transmembrane protein on B-lymphocytes. The attached antibody activates an immune response causing destruction of these activated B cells. A decreased number of CD 20 lymphocytes results in diminished activity of RA.  Rituxan® is administered by infusion on a regular schedule usually every 6 months

Interleukin-17 (IL-17) inhibitors

Interleukin-17 is a protein produced by immune cells that function as a messenger between cells playing an important role in inflammation.  Antibodies that target the IL-17 pathways are used for the treatment of several conditions in which the IL-17 pathway has a role, including AS, psoriasis and psoriatic arthritis.  IL-17 therapies include

  • Cosentyx (secukinumab) is an anti-IL-17 monoclonal antibody that blocks the effects of IL-17 leading to an improvement in IL-17 associated symptoms.
  • Taltz (ixekisumab) is an anti IL-17 monoclonal antibody that blocks the effects of IL-17.

Side effects associated with the use of IL-17 inhibitors include an increased risk of infections. Another very small risk is the development or worsening of inflammatory bowel disease.

Non-biologic DMARDs

  • Methotrexate
  • Leflunomide
  • Sulfasalazine
  • Hydroxychloroquine

Corticosteroids

Systemic corticosteroids are effective in controlling the inflammatory components of RA. Corticosteroids are the most powerful and predictable remedy inducing immediate relief of joint inflammation in RA. Corticosteroids prescribed in low doses (5 to 10 mg) have a modest effect on reducing the rate of x-ray detected joint destruction. The side effects of corticosteroids include hypertension, diabetes, cataracts, and obesity.

Treatment of Rheumatoid Nodules

Treatment of rheumatoid nodules is typically directed at nodules causing symptoms or functional problems.  Injections of glucocorticoids (steroids) may help shrink nodules; sometimes surgery is necessary if rheumatoid nodules become infected or cause severe symptoms.

There is no specific drug therapy directed at treating rheumatoid nodules; however, disease-modifying antirheumatic drugs (DMARDs) can reduce the size of rheumatoid nodules. If nodules are thought to be a result of methotrexate treatment, a change in medication regimen may help; however, this decision must be carefully made on an individual basis.

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References


Borenstein DG, Wiesel SW, Boden SD: Low Back and Neck Pain: Comprehensive Diagnosis and Management. 3rd Edition. Philadelphia: W. B. Saunders, 2004, pg 921