bone, joint, and muscle disorders
Rheumatoid Arthritis (RA)
Medications for Rheumatoid Arthritis
The main goal of drug treatment is to reduce inflammation and thereby prevent erosions, progression of the disease, and loss of joint function. The main categories of medications used to treat rheumatoid arthritis are Nonsteroidal anti-inflammatory drugs (NSAIDs) None Disease-modifying antirheumatic drugs (DMARDs) None Corticosteroids None Biologic agents None Many of these medications are used in combination. For example, doctors may prescribe two DMARDs together or a corticosteroid plus a DMARD. However, the best combinations of medications are not yet clear. Typically, biologic agents are not used in combination with other biologic agents because these combinations increase the frequency of infections. All the categories of drugs have potentially serious side effects that must be looked for during treatment. Nonsteroidal Anti-Inflammatory Drugs can be used to treat the symptoms of rheumatoid arthritis. They do not prevent the damage caused by rheumatoid arthritis from progressing and thus should not be considered the primary treatment. (See also table that reduce pain but not inflammation. However, NSAIDs should generally not be taken by people who have a history of Peptic Ulcer Disease —including stomach ulcers or duodenal ulcers—because NSAIDs can upset the stomach and cause ulcers to bleed. Medications called proton pump inhibitors (such as Other possible side effects of NSAIDs may include headache, confusion, elevation of blood pressure, worsening of kidney function, swelling, and decreased platelet function, causing bruising or bleeding. People who get hives, inflammation and swelling in the nose, or asthma after they takeaspirinmay have the same symptoms after taking other NSAIDs. NSAIDs may increase the risk of heart attacks and strokes. The risk appears to be higher if the drug is used at higher doses and for longer periods of time. Aspirinis no longer used to treat rheumatoid arthritis because effective doses are often toxic. Thecyclooxygenase (COX-2) inhibitors(coxibs, such ascelecoxib) are NSAIDs that act similarly to the other NSAIDs but are slightly less likely to damage the stomach and do not affect platelet function and cause bruising or bleeding like the other NSAIDs. However, if a person also takesaspirin, stomach damage is almost as likely to occur as with other NSAIDs. Caution should be taken with use of coxibs and probably all NSAIDs for long periods or by people with risk factors for heart attack and stroke. DMARDs, such asmethotrexate,hydroxychloroquine,leflunomide, andsulfasalazine, slow the progression of rheumatoid arthritis and are given to nearly all people with rheumatoid arthritis. Doctors typically prescribe these drugs as soon as the diagnosis of rheumatoid arthritis is made. Many take weeks to have an effect. Even if pain is decreased with NSAIDs, a doctor will likely prescribe a DMARD because the disease may otherwise progress even if symptoms are lessened. (See also table.) About two thirds of people improve overall, and complete remissions are becoming more common. The progression of arthritis usually slows, but pain may remain. People should be fully aware of the risks of DMARDs and monitored carefully for evidence of toxicity. Combinations of DMARDs may be more effective than single drugs. For example,hydroxychloroquine,sulfasalazine, andmethotrexatetogether are more effective thanmethotrexatealone or the other two together. Also, combining biologic agents with a DMARD is often more effective than using a single drug or certain combinations of DMARDs. For example,methotrexatecan be combined with a TNF inhibitor. Methotrexateis taken by mouth once weekly. It is anti-inflammatory at the low doses used to treat rheumatoid arthritis. It is very effective and begins to work within 3 to 4 weeks, which is relatively rapid for a DMARD. The liver can scar, but this scarring most often can be detected by monitoring with regular blood tests and reversed before major damage develops. People must refrain from drinking alcohol to minimize the risk of liver damage. Bone marrow suppression (suppression of the production of red blood cells, white blood cells, and platelets) may occur. Blood counts should be tested about every 2 to 3 months in all people taking the drug. Inflammation of the lung (pneumonitis) is rare. Inflammation in the mouth and nausea can also develop. Severe relapses of arthritis can occur aftermethotrexateis discontinued. Folate (folic acid) tablets may decrease some of the side effects, such as mouth ulcers. Rheumatoid nodules may enlarge withmethotrexatetherapy. Hydroxychloroquineis given daily by mouth. Side effects, which are usually mild, include rashes, muscle aches, and eye problems. However, some eye problems can be permanent, so people takinghydroxychloroquinemust have their eyes checked by an ophthalmologist before treatment begins and every 12 months during treatment. If the medication has not helped after 9 months, it is discontinued. Otherwise,hydroxychloroquinecan be continued as long as necessary. Leflunomideis taken daily by mouth and has benefits that are similar to those ofmethotrexatebut it is less likely to cause suppression of blood cell production in the bone marrow, abnormal liver tests, or inflammation of the lungs (pneumonitis). It can be given at the same time asmethotrexate. The major side effects are rashes, liver dysfunction, hair loss, diarrhea, and rarely nerve damage (neuropathy). Sulfasalazineis initially given by mouth and can relieve symptoms and slow the development of joint damage.Sulfasalazinecan also be used in people who have less severe rheumatoid arthritis or added to other medications to boost their effectiveness. The dose is increased gradually, and improvement usually is seen within 3 months. Becausesulfasalazinemay quickly cause a person's white blood cell count to become very low (neutropenia), blood tests are done after the first 2 weeks and then about every 12 weeks while the person is taking the drug. Like the other DMARDs, it can cause stomach upset, diarrhea, liver problems, blood cell disorders, and rashes. In males,sulfasalazinemay cause a low sperm count, which is reversible. Corticosteroids are potent anti-inflammatory drugs that suppress the immune system. Corticosteroids, such asprednisone, are the most dramatically effective drugs for reducing inflammation and symptoms of rheumatoid arthritis anywhere in the body. (See also table.) There is some controversy as to whether corticosteroids can slow the progression of rheumatoid arthritis. Furthermore, the long-term use of corticosteroids almost invariably leads to side effects, potentially involving almost every organ in the body (see Corticosteroids: Uses and Side Effects ). Consequently, doctors usually reserve corticosteroids for short-term use in the following situations: When beginning treatment for severe symptoms (until a DMARD has taken effect) In severe flare-ups when many joints are affected They are also useful in treating rheumatoid inflammation outside of joints, for example, in the membranes covering the lungs (pleura) or in the sac surrounding the heart (pericardium). Because of the risk of side effects, the lowest effective dose is almost always used. When corticosteroids are injected into a joint, the person does not get the same side effects as when taking a corticosteroid by mouth (orally) or vein (intravenously). Corticosteroids can be injected directly into affected joints for fast, short-term relief of pain and swelling. When used for a long time, corticosteroids may cause weight gain, high blood pressure, diabetes, thinning and bruising of the skin, glaucoma and other eye problems such as cataracts, and increase the risk of certain infections. Corticosteroids are the strongest drugs available for reducing inflammation in the body. They are useful in any condition in which inflammation occurs, including rheumatoid arthritis and other connective tissue disorders, multiple sclerosis, and in emergencies such as brain swelling due to cancer, asthma attacks, and severe allergic reactions. When inflammation is severe, use of these drugs is often lifesaving. Corticosteroids can be Given by vein (intravenously—especially in emergency situations) Taken by mouth (orally) Directly applied to the inflamed area (topically; for example, as eye drops or as skin creams) Inhaled (as in inhaled versions for the lungs, used to treat disorders such as asthma and COPD) Injected into a muscle (intramuscularly) Injected into a joint For example, corticosteroids can be used as an inhaled preparation for treatment of asthma. They can be used as a nasal spray to treat hay fever ( Allergic Rhinitis ). They can be used as eye drops to treat eye inflammation ( Corticosteroids are prepared synthetically to have the same action ascortisol(orcortisone), a steroid hormone produced by the outer layer (cortex) of the adrenal glands—hence the name “corticosteroid.” Many synthetic corticosteroids are, however, more powerful thancortisol, and most are longer acting. Corticosteroids are chemically related to, but have different effects than, anabolic steroids (such astestosterone) that are produced by the body and sometimes abused by athletes. Examples of corticosteroids areprednisone,dexamethasone,triamcinolone,betamethasone,beclomethasone,flunisolide, andfluticasone. All of these drugs are very strong (although strength depends on the dose used).Hydrocortisoneis a milder corticosteroid that is available in over-the-counter skin creams. Corticosteroids reduce the body’s ability to fight infections by reducing inflammation, typically when they are taken by mouth or given by vein. Because of this side effect, they are used with extreme care when infections are present. Oral and intravenous use may cause or worsen high blood pressure, heart failure, diabetes, peptic ulcers, and osteoporosis. Therefore, corticosteroids are used in such conditions only when their benefit is likely to exceed their risk. When they are taken by mouth or by injection for more than about 2 weeks, corticosteroids should not be stopped abruptly. This is because corticosteroids inhibit the production ofcortisolby the adrenal glands, and this production must be given time to recover. Thus, at the end of a course of corticosteroids, the dose is gradually reduced. It is important for a person who takes corticosteroids to follow the doctor’s instructions on dosage very carefully. The long-term use of corticosteroids, particularly at higher doses and particularly when given by mouth or vein, invariably leads to many side effects, involving almost every organ in the body. Common side effects include thinning of the skin with stretch marks and bruising, high blood pressure, elevated blood sugar levels, cataracts, puffiness in the face (moon face) and abdomen, thinning of the arms and legs, poor wound healing, stunted growth in children, loss of calcium from the bones (which can lead to osteoporosis), hunger, weight gain, and mood swings. Inhaled corticosteroids and corticosteroids that are applied directly to the skin have far fewer side effects than corticosteroids given by mouth, vein, or injection. A biologic agent is something made from a living organism, often using cells in a laboratory. Many biologic agents used to treat rheumatoid arthritis are antibodies. Biologic agents used to treat rheumatoid arthritis includeabatacept,rituximab, tumor necrosis factor (TNF)–inhibiting drugs (adalimumab,certolizumab pegol,etanercept,golimumab, andinfliximab), an interleukin-1 receptor blocker (anakinra), and interleukin-6 receptor blockers (tocilizumabandsarilumab). (See also table.) Biologic agents may suppress the inflammation so that corticosteroids can be avoided or given in lower doses. But by interfering with the immune system, biologic agents may increase the risks of infection and certain cancers. Because treatment with biologic agents increases the risk of infection, before starting treatment with a biologic agent people should be up to date on vaccinations (see table). Etanercept,infliximab,golimumab,certolizumab pegol,andadalimumabare TNF inhibitors and can be dramatically effective for people who do not respond sufficiently tomethotrexatealone. Etanerceptis given once a week by injection under the skin. Infliximabis given by vein. After the first dose ofinfliximabis given, the next two doses are given at 2 and at 6 weeks. Theninfliximabis given every 8 weeks. Golimumabis given by injection under the skin once every 4 weeks. Certolizumab pegolis given by injection under the skin. After the first dose, the next two doses are given at 2 and at 4 weeks. Then the drug is given at 2-week or 4-week intervals, depending on the dose. Adalimumabis injected under the skin once every 1 to 2 weeks. TNF is an important part of the body’s immune system, so inhibition of TNF can impair the body’s ability to fight infections, particularly a reactivated tuberculosis infection. These drugs should be avoided in people who have active infections and should be discontinued before major surgery.Etanercept,infliximab, andadalimumabcan be and are often used withmethotrexate. People who have severe heart failure should not take high doses ofinfliximab. Side effects of TNF inhibitors include the potential risk of reactivation of infection (particularly Tuberculosis (TB) and Anakinrais an interleukin-1 (IL-1) receptor blocker, which means it interrupts one of the major chemical pathways involved in inflammation.Anakinrais given as a single daily injection under the skin. Pain and itching at the injection site are the most common side effects. IL-1 is part of the immune system, so inhibiting IL-1 can impair the ability to fight infections.Anakinracan also suppress production of white blood cells. It should not be used with TNF inhibitors. It is prescribed less often because it must be given every day. can cause effects while it is being given, such as rashes, nausea, back pain, itching, and high or low blood pressure. It can cause severe liver damage by reactivating Hepatitis B, Acute in people who had previously been infected with this virus. The COVID-19 Vaccine may be less effective in people taking Abataceptis another biologic agent that interferes with the communication between cells that coordinates inflammation. Side effects include lung problems, headache, increased susceptibility to infection, and upper respiratory infection. The first injection in the vein takes over 30 minutes to complete. After that, it is injected in a vein or under the skin at 2 weeks and at 4 weeks after the first dose and every 4 weeks thereafter. Sarilumabis an IL-6 receptor blocker, which means it interrupts one of the major chemical pathways involved in inflammation. This drug is given to people who have not been helped by or who cannot tolerate DMARDs.Sarilumabcauses suppression of blood cell production in the bone marrow (neutropenia), suppression of platelet production in the bone marrow (sometimes with increased susceptibility to bleeding), and increased liver enzymes. It is given by injection under the skin (subcutaneously) once every 2 weeks. . Side effects include infection (such as Tuberculosis (TB) ), suppression of blood cell production in the bone marrow (neutropenia), .) Because treatment with JAK inhibitors increases the risk of infection, including herpes zoster infection, people should be Shingles Vaccine before starting treatment with a JAK inhibitor. increases the risk of nonmelanoma skin cancer, Dyslipidemia (hypercholesterolemia), and . Side effects include nonmelanoma skin cancer and Dyslipidemia . Upadacitinibis given to adults with moderately to severely active rheumatoid arthritis whenmethotrexatehas not been effective enough. 