Risks and Benefits of Rheumatoid Arthritis Drugs

Research has shown that in most people with early rheumatoid arthritis, use of combination therapy reduces disease activity and increases the ability to function for at least two years. But few people achieve permanent remission, making it likely that you will have to take rheumatoid arthritis medication for the rest of your life. Your treatment will probably require a combination of medications from three drug categories: NSAIDs, corticosteroids and DMARDs.

In the past, people with newly diagnosed rheumatoid arthritis were treated first with an over-the-counter pain reliever, such as acetaminophen or one of the over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. Only when the disease worsened would doctors begin to prescribe stronger medications, and by the time a disease-modifying antirheumatic drug (DMARD) was started, some joint damage was already permanent.

In recent years, the prognosis has improved dramatically, thanks to earlier use of the powerful new DMARDs. Current guidelines specify DMARDs as the first drugs to use in individuals who are newly diagnosed. This more aggressive approach makes long-term remission an attainable goal for many more people.

However, the newest disease-modifying drugs—biologic response modifiers—are very expensive, typically costing more than $1,000 per month. When you add this cost to the expense of your other arthritis medications, X-rays, lab tests, visits to your doctor, physical therapy, treatment for depression (which is common in rheumatoid arthritis patients), and indirect costs related to disability and missed work, it is obvious that having rheumatoid arthritis can be a significant financial burden for many people.

Unfortunately, insurance companies often press for the lowest-cost drugs and treatment. Your health-care provider can help you balance monetary concerns with the need to prevent disability. You also may be able to get financial assistance from some of the pharmaceutical companies that manufacture the drugs. In the future, a less expensive alternative to biologics—known as biosimilars—may offer some financial relief, but concerns about safety and effectiveness need to be resolved first.

DMARDs

DMARDs have anti-inflammatory properties and, more important, the ability to slow the disease process by suppressing the immune system. Because DMARDs reduce your immune response, once you start taking one of these medications it’s important to check with your doctor before getting any vaccinations. Notify your doctor if you develop any signs of an infection, such as chills, fever, sore throat or cough.

Doctors divide DMARDs into two main groups: the older DMARDs that they have been prescribing for decades, such as methotrexate, and the newer biologic response modifiers, the first of which was approved in 1998. The newer group of DMARDs acts directly on the immune system by inhibiting cytokines, proteins that are involved in inflammation. A newer DMARD, tofacitinib (Xeljanz)—the first oral biologic for RA—has a different target.

Traditionally, doctors have prescribed older, less expensive, oral DMARDs for most people who were newly diagnosed with rheumatoid arthritis. Rheumatologists often chose oral methotrexate as the initial therapy because of its long track record of effectiveness, low risk of side effects and low cost. However, recent guidelines from the American College of Rheumatology now recommend basing initial treatment on a number of factors, including levels of disease activity and the presence or absence of features that indicate a poor prognosis, such as limitations in your ability to function, positive rheumatoid factor or bony erosions on X-ray.

This means that in some cases, initial treatment with an older DMARD alone, such as methotrexate, may be appropriate, while others may need a combination of old and new DMARDs. The new biologic DMARDs also often work for people who have not been helped by older DMARDs. Typically in such cases, they are added to the treatment regimen when an older DMARD, such as methotrexate, does not relieve symptoms.

Most of the biologic DMARDs—adalimumab (Humira), anakinra (Kineret), certolizumab (Cimzia), etanercept (Enbrel) and golimumab (Simponi)—are self-injected into the layer of fat directly under the skin. If you take one of these injectable medications, a health-care professional will teach you or your caregiver the correct injection technique and help with the first few injections. These drugs must be stored in the refrigerator.

Abatacept (Orencia), infliximab (Remicade), rituximab (Rituxan) and tocilizumab (Actemra) are administered via intravenous (IV) infusion (that is, the drug flows through an IV line placed in your arm) at your doctor’s office or an outpatient clinic. This usually takes about two hours. During these infusions, some people experience severe allergy-like reactions, with fever, chills, nausea and shortness of breath. Because of this risk, a doctor or nurse should always monitor you during an infusion. Some doctors advise taking an antihistamine, acetaminophen and/or prednisone before the infusion to help prevent these reactions.

Tofacitinib, the newest biologic agent approved by the FDA for the treatment of rheumatoid arthritis, is the first of a new class of medications called Janus kinase (JAK) inhibitors. JAKs are enzymes in white blood cells that signal other cells to produce inflammation-promoting cytokine. Researchers believe that prolonged JAK signaling may be central to the development of rheumatoid arthritis. Thus, JAK inhibitors, rather than blocking pro-inflammatory cytokines, block the signals that tell cytokines to activate.

Tofacitinib is taken orally as a 5-mg pill twice a day. This medication is an option for adults with moderate to severe rheumatoid arthritis who have had an inadequate response to or cannot tolerate methotrexate.

If your doctor is considering prescribing one of the biologic response modifiers, be sure he or she is aware of any other medical problems you have and medications you take. For example, let your doctor know if you have an infection, heart failure, acute or chronic hepatitis B or C or a neurological disorder or have had skin cancer. Also let your doctor know if you are about to undergo surgery. Finally, be sure that you have a test for tuberculosis before starting therapy with any of the biologic response modifiers. Nonsteroidal anti-inflammatory drugs (NSAIDs) NSAIDs reduce pain and inflammation but they don’t prevent joint destruction or worsening of rheumatoid arthritis. That and findings that regular use of NSAIDs can elevate the risk of heart attack and stroke are reasons why they are no longer recommended as the sole treatment for rheumatoid arthritis. NSAIDs are instead used with DMARDs to provide additional relief from pain and inflammation when other avenues of pain relief have been tried without success.

Aspirin is an exception. It is less expensive than other NSAIDs and may lower the risk of heart disease. Unless there is some reason not to use it (such as an allergy), aspirin is the NSAID of choice to reduce rheumatoid arthritis inflammation. The dosage can range from 2,400 to 5,400 mg per day, taken in divided doses. Gastrointestinal irritation, however, often limits the amount of aspirin people can tolerate.

People with rheumatoid arthritis, especially older people, are twice as likely as those with osteoarthritis to develop gastrointestinal ulcers and other serious complications from NSAIDs. Some (but not all) studies suggest that the newer NSAIDs—COX-2 inhibitors—might produce fewer gastrointestinal side effects. Due to their adverse cardiovascular effects, however, the only COX-2 inhibitor currently available is celecoxib (Celebrex).

As in the treatment of osteoarthritis, the goal for rheumatoid arthritis therapy is to use the NSAID that provides the greatest benefit while producing the fewest risks and side effects. It may require trial and error, however, to find the best option because some people respond better to one NSAID than to another.

Corticosteroids

Typically, corticosteroid drugs are given in pill form, but as with osteoarthritis, injecting corticosteroids into the most affected joints is safe and highly effective for rheumatoid arthritis.

Low oral doses of the corticosteroid drug prednisone usually produce a rapid and dramatic improvement in rheumatoid arthritis symptoms by reducing inflammation and suppressing the immune system. Some studies suggest that corticosteroid treatment may also slow the rate of joint damage. Inflammation and joint damage frequently recur or get worse, however, once a corticosteroid is discontinued.

Because of the relief corticosteroids provide, you may be tempted to continue using them for long periods of time. But doing so can result in serious side effects: stomach ulcers, weight gain with fat deposits in the trunk (especially the upper back), diabetes, high blood pressure, thinning of the skin with easy bruising and poor wound healing, acne, weakness, muscle wasting, cataracts, increased susceptibility to infections, psychiatric disturbances and osteoporosis.

Corticosteroids are best reserved for short-term treatment in people who are waiting for a DMARD to take effect. They are also used for incapacitating flares, for severe manifestations of rheumatoid arthritis affecting other organs (such as vasculitis and scleritis), or when alternative drugs are unsuccessful or cause side effects that are intolerable.

Because osteoporosis develops in as many as 50 percent of people taking corticosteroids, the American College of Rheumatology recommends using the lowest effective dose, along with 1,200 mg of calcium and 800 IU of vitamin D daily. Experts now recommend getting most of your calcium through dietary sources, with a supplement if needed to reach the recommended daily dose. It’s also important to avoid smoking and alcohol, to maintain a healthy weight and to get regular weight-bearing exercise such as walking.

A bone mineral density test should be done before beginning treatment, with follow-up scans every one or two years to monitor changes in bone density. An osteoporosis medication, such as alendronate (Fosamax) or risedronate (Actonel), is often recommended as well.

The adrenal glands stop producing steroids when you are taking a corticosteroid, so when the medication is discontinued after being used at high doses or for a long time, the dosage must be reduced very slowly to give the adrenal glands a chance to resume steroid production. This will also help prevent a disease flare.