Description of Biologics: Biologics are new class of drugs that have been used since 1998 and have been studied for almost 10 years. Overall, they have been given to more than 600,000 people worldwide. A “biologic” drug copies the effects of substances naturally made by your body's immune system. Biologic agents are genetically engineered drugs – meaning that human genes that normally guide the production of these natural human immune proteins (i.e., an antibody to TNF) are used in non-human cell cultures to produce large amounts of a biologic drug. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation. These new biologic agents can specifically affect some of the abnormalities of the immune system that lead to the joint inflammation and other abnormalities seen in rheumatoid arthritis and so help treat its symptoms.
Uses of Biologics: Biologic agents have been approved by the FDA to treat moderate to severe rheumatoid arthritis that has not responded to an adequate trial of one or more of the traditional disease modifying antirheumatic drugs (DMARDs). Because of their expense and side effects, most people with mild to moderate rheumatoid arthritis are treated with methotrexate before a biologic agent is used. Biologic agents may be used alone, but are often given in conjunction with other DMARDs (e.g., methotrexate, leflunomide, hydroxychloroquine, sulfasalazine), to increase the benefit and limit potential side effects. When patients start using biologic agents as an arthritis medication, they usually also remain on their current dose of nonsteroidal anti-inflammatory (NSAID) and/or corticosteroid medicines. Some of the TNF inhibitors have been approved for use in juvenile arthritis, Crohn’s colitis, psoriatic arthritis, ankylosing spondylitis and psoriasis.
How Biologics Work: Currently available biologic agents act as inhibitors of the cytokines IL-1 or TNF. Cytokines are messenger molecules made by many of the body's cells that act to excite other immune system cells. Interleukin-1 and tumor necrosis factor (TNF) are made in large amounts in rheumatoid arthritis and other forms of inflammation. In these diseases, TNF or IL-1 act to increase inflammation, similar to the effect of gasoline on a fire. However, in rheumatoid arthritis TNF or IL-1 acts to excite the inflamed joint. Hence, these cytokines amplify and worsen inflammation and joint damage. Biologic agents were made to specifically attach to TNF or IL-1 and inhibit or inactivate them. Table 1 compares the different biologic drugs used in rheumatoid arthritis.
NSAIDs and DMARDs:
NSAIDs NonSteroidal Anti-Inflammatory Drugs. These drugs work by limiting the body's production of hormone-like substances called prostaglandins, which are involved in causing pain and inflammation. For many arthritis-related diseases NSAIDs provide some symptomatic relief and therefore can be an important part of a treatment plan.
NSAIDs are quite efficient at reducing both pain and inflammation, but they also can carry some significant side effects, including stomach irritation and gastric ulcers.
This medications works by reducing hormones that cause inflammation and pain in the body. Naproxen is used to treat pain or inflammation caused by conditions such as arthritis, ankylosing spondylitis, tendinitis, bursitis, gout, or menstrual cramps.
This medication affects the body in several ways; it eases symptoms of fever, pain, and inflammation and reduces the ability of the blood to clot. Aspirin relieves the mild to moderate discomfort caused by a variety of conditions including arthritis, headaches, infections, menstrual cramps or pain, minor injuries, and other conditions. It can also be part of a total treatment aimed at reducing the risk of heart attacks or stroke.
This medication works by reducing hormones that cause inflammation and pain in the body. It is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury.
Nabumetone DMARD Disease-Modifying AntiRheumatic Drugs, have the potential to control inflammation and limit joint damage.
is a DMARD used to slow the disease process and treat the pain and swelling of rheumatoid arthritis. To improve methotrexate's effectiveness, physicians may increase the oral dosages or try intramuscular injections of the medication. The potential side effects and benefits are virtually the same whether it is given orally or by injection. Liver damage remains the main concern, and is monitored by frequent blood tests.
is similar to the antibiotic tetracycline, generally is considered to be one of the safer DMARDs. The most common side effects with using minocycline are upset stomach, dizziness, discolored fingernails and rashes or dark pigmentation of the skin.
Minocycline is effective in about 60 percent of people with RA who use it. However, it often is not prescribed because it does not have FDA labeling approval for this use, and it is a relatively weak DMARD compared with methotrexate, leflunomide or the biologics Enbrel, Humira, Kineret, Orencia, Remicade and Rituxan. It isn’t the antibiotic properties, but the effects on the immune system and the ability to inhibit enzymes that break down cartilage and connective tissue that make minocycline so effective.
These drugs are often referred to as "super aspirins." These drugs were developed principally to reduce the risk of gastrointestinal side effects. The studies have clearly shown they in fact do result in fewer GI side effects, but have not shown that these drugs actually relieve pain more effectively than other medications. However, patients respond quite differently to this treatment and for some, the Cox-2 drugs relieve their pain more effectively than any drugs they have tried.
Anti Inflammatory Drugs: While anti inflammatory drugs may be helpful for many patients, they are not a panacea and are also capable of causing many potential side effects. They should only be used with the advice of a knowledgeable physician. Anti-inflammatory drugs act by blocking the effects of prostaglandins. This effect is a two-edged sword. Blocking inflammation is one edge; potential side-effects are the other.
Anti malarials: used to treat malaria long before they were used to treat arthrits, drugs such as hydroxychloroquine and chloroquine are a mainstay of treatment for milder forms of inflammatory arthritis.
Leflunomide: is another anti-metabolite used in the treatment of rheumatoid arthritis and psoriatic arthritis. While effective, it has been supplanted, for the most part, by the use of biologic therapy.
Cyclosporine: is a disease modifying drug for rheumatoid arthritis that was "borrowed" from the organ transplant surgeons. Genrally used in combination with methotrexate, its effectiveness is sometimes limited by its toxicity.
Gold: Gold treatment includes different forms of gold salts used to treat arthritis. Gold is an effective medicine for controlling some types of arthritis and related diseases. In some people, it helps relieve joint pain and stiffness, reduce swelling and bone damage, and reduce the chance of joint deformity and disability, it helps to keep the disease under control.
Prednisone: Prednisone is used alone or with other medications to treat the symptoms of low corticosteroid levels. Prednisone is also used to treat other conditions in patients with normal corticosteroid levels. These conditions include certain types of arthritis; severe allergic reactions; multiple sclerosis; lupus; and certain conditions that affect the lungs, skin, eyes, kidneys blood, thyroid, stomach, and intestines. Prednisone is also sometimes used to treat the symptoms of certain types of cancer. Prednisone is in a class of medications called corticosteroids. It works to treat patients with low levels of corticosteroids by replacing steroids that are normally produced naturally by the body. It works to treat other conditions by reducing swelling and redness and by changing the way the immune system works.
Sulfasalazine:The drug sulfasalazine is a 5-ASA compound, and is the combination of two substances: sulfapyridine and an aspirin-like compound. It works to reduce the inflammation in the colon caused by ulcerative colitis and then as a maintenance therapy to maintain remission. Sulfasalazine may also be used to treat Crohn's disease in some cases.
Cyclosporine: is a potent immunosuppressant medication that is considered a disease modifying antirheumatic drug (DMARD) because it not only decreases the pain and swelling of arthritis but it may also prevent joint damage and reduce the risk of long term disability.
Hydroxychloroquine: belongs to the family of medicines called antiprotozoals. Protozoa are tiny, one-celled animals. Some are parasites that can cause many different kinds of infections in the body. This medicine is used to prevent and to treat malaria and to treat some conditions such as liver disease caused by protozoa. It is also used in the treatment of arthritis to help relieve inflammation, swelling, stiffness, and joint pain and to help control the symptoms of lupus erythematosus.
Cyclophosphamide: Cytotoxic drugs, such as methotrexate, Cytoxan, and Imuran are used to treat rheumatoid arthritis and some other rheumatic diseases. There are potentially serious side effects associated with these drugs, but methotrexate appears to have the best safety profile.
None are completely safe, and the potential risk of side effects can be frightening. Anytime you interfere with one bodily process you may interfere with others, sometimes in undesirable ways. But the dangers of untreated arthritis, in most cases, far outweigh the risks of the drugs used to treat it. Each day, medications ease pain, prevent joint destruction and improve the lives of countless people with arthritis and related conditions. In some cases, medications can literally save lives.
Life is full of risks. Sometimes we have to risk experiencing a side effect to gain the benefits of an arthritis medication. The key is weighing risks against potential gain. Your doctor can help you weigh those risks and choose the drugs that provide the most help and do the least possible harm.