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. 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 side effects.
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.
Some NSAIDs can cause problems such as gastrointestinal bleeding, and people who use these drugs on a regular basis may also be prescribed medication to help protect their gastrointestinal tract.1 Certain types of NSAIDS also have cardiovascular risks.
Steroids known as glucocorticoids may be used on short-term basis to reduce joint inflammation. Depending on the situation, they may be taken orally, injected into a muscle, or injected directly into an affected joint. Steroids can rapidly improve symptoms, and may be especially useful during a flare-up of symptoms or while waiting for a slower-acting drug (such as the DMARDs) to take effect.2
Possible side effects of steroids include bone loss, weight gain, cataracts, and increases in blood sugar and blood pressure. Long-term use carries a greater risk of side effects than short-term use. include hypertension, diabetes, cataracts, bone loss,obesity.
Spasms in spinal muscles in AS patients cause pain and limitation of motion. The addition of a muscle relaxant to a NSAID helps decrease muscle pain and tightness. The most common side effect of muscle relaxants is sleepiness. Taking the medicine early in the evening can minimize the possibility of tiredness.
Disease-Modifying Agents (DMARDs)
DMARDs are drugs that work more slowly than NSAIDs; they however do more than just relieve painful, swollen joints: they have the capability of modifying the progression of disease. There are two categories of DMARDs: biologic (created to be similar to proteins found in the body) and non biologic.
Methotrexate is a commonly used DMARD, but several other options are available. In some cases, a combination of DMARDs may be used. These drugs are taken orally (by mouth). It generally takes a few weeks or months for them to take effect.
Side effects vary; for methotrexate, possible side effects include nausea, abnormal liver function tests, mouth sores, rash, diarrhea, changes in blood cell counts, lung problems, and sun sensitivity.
If initial treatment does not adequately control symptoms or there is evidence of disease progression treatment may involve a newer type of medication known as a biologic.4 Biologic DMARDs interfere with specific parts of the immune system that drive inflammation.
Anti-Tumor Necrosis Factor Inhibitors (TNFi)
An inflammatory cytokine, 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 these disease-associated symptoms. There are a number of anti-TNF therapies available for the treatment of AS. PsA, RA and other condtions 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 use of specific anti-TNFi drugs is based on personal preference related to injections versus infusion and frequency of dosing, and physician preference.
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 evaluation.
Interleukin 12 and 23 Inhibitors
Interleukin (IL) 12 and 23 are released in increased amounts in skin of individuals with psoriasis. IL-23 stimulates the production of Th17 lymphocytes that are active in psoriasis and psoriatic arthritis. IL-12 stimulates CD4+ T lymphocytes to become activated facilitating an inflammatory response.
- Stelara (Ustekinumab) is a human monoclonal antibody directed against a common portion of both IL-12 and 23. The antibody blocks the receptor for IL-12 and 23 preventing activation.
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.
Selective T-cell Costimulator Inhibitor
Activation of the immune systems lymphocytes requires a sequence of signals between cells. The immune response that results in psoriatic arthritis can be diminished if these secondary signals are blocked.
- Orencia (Abatacept) is a fusion protein that inhibits antigen-presenting cells from delivering co-stimulatory signals that activate T lymphocytes. Orencia is a CTLA4-Ig fusion protein used for the treatment of RA and PsA. Orencia® is administered by monthly infusions or subcutaneous injections.
Phosphodiesterarses (PDE 4) Inhibitors
Phosphodiesterases are enzymes that modify chemicals that are energy sources for cell function. Energy in these pathways results in the production of a number of cell products including those that result in disease inflammation. PDE4 has specificity for cyclic adenosine monophosphate and is found in inflammatory cells like B and T lymphocytes.
- Otezla(Apremilast) is a PDE4 inhibitor that is effective in controlling the manifestations of psoriasis and psoriatic arthritis. As opposed to biologic agents with increased risk of infections and malignancy, gastrointestinal upset particularly diarrhea is the primary side effect of Otezla.
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.
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.
1 Singh JA, Furst DE, Bharat A et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care & Research. 2012;64:625-639.
2Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. The Lancet. 2010;376:1094-1108.