Rheumatoid arthritis drugs side effects

It is estimated that more than 50 million Americans have arthritis, which is the top cause of disability in the United States. The disease affects women and older adults more often than men and younger folks, though people of all sexes, ages and races can have it. There are quite a few drugs available for treatment, but it is important to know about the bothersome or even dangerous side effects they can cause — even the ones you get over the counter.

First, Arthritis 101

Over 100 types of arthritis and related conditions exist, but the most common are osteoarthritis, rheumatoid arthritis and psoriatic arthritis. Osteoarthritis causes a breakdown of cartilage -– the tissue covering the bones where they meet to form a joint. Without the cushioning in between, the bones can eventually begin rubbing against each other, causing symptoms of pain, stiffness and swelling. Age, excess weight, and having a history of certain injuries are risk factors for osteoarthritis.

Rheumatoid and psoriatic arthritis are inflammatory types of the disease that are autoimmune disorders, which means the immune system mistakes healthy cells for invasive ones and tries to fight them off. When working properly, the immune system creates inflammation when it attacks foreign cells. In the case of rheumatoid arthritis, the immune system mistakenly targets the joints with an excessive amount of inflammation, leading to symptoms like swelling, fatigue, pain and stiffness –- especially in the morning.

In psoriatic arthritis, the immune system targets the joints and skin and causes similar symptoms to those of rheumatoid arthritis, plus additional ones. For example, swelling may give fingers and toes a sausage-like appearance in people with psoriatic arthritis in particular, and this symptom can help doctors tell the disease apart from rheumatoid arthritis, which typically involves swelling in a single joint instead. Certain skin and nail changes are also unique to psoriatic arthritis.

Though the causes of autoimmunity are not entirely clear, experts think it may result from a combination of genetic and environmental factors. Smoking may trigger rheumatoid arthritis in some people, while infection may be the trigger for psoriatic arthritis.

Arthritis Drug Side Effects

The good news is that there are several treatment options, many of which are quite effective in slowing down the damage related to the disease as well as easing symptoms. Disease modifying antirheumatic drugs (DMARDs) and biologics –- such as Humira (adalimumab) and Remicade (infliximab) — alleviate symptoms and slow the progression of joint damage in inflammatory arthritis, and nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation.

As with all drugs, however, there are potential side effects to be aware of, and you shouldn’t wait for your doc to take notice, suggests a 2016 study of patients with rheumatoid arthritis. Researchers at the University of Alabama found that the widely used arthritis drug methotrexate is “accompanied by many patient-reported side effects and tolerability problems that may be under-recognized by physicians,” including diarrhea, fatigue, hair loss and more. These effects can influence whether patients continue taking the drug or take it as often as they are supposed to.

Other arthritis meds can be troublesome too, says Mohamed A. Jalloh, PharmD, assistant professor at Touro University California College of Pharmacy and spokesman for the American Pharmacists Association: “When looking at common medications for arthritis, the most common side effects are nausea, vomiting, abdominal pain, anemia, headache and edema.”

He explains that there are a variety of ways that a drug can cause side effects, but in general, medications interact with structures (called receptors) in the body that resemble the real target of the medication. In other words, they go where they shouldn’t — and cause problems.

The most common side effects associated with common arthritis medications are nausea, vomiting, abdominal pain, anemia, headache and edema.

Anemia is a shortage of red blood cells or an oxygen-carrying protein in these cells called hemoglobin. Some drugs that are used to treat arthritis, including non-steroidal anti-inflammatory drugs (NSAIDs) such as Advil (ibuprofen) and Aleve (naproxen), Tylenol (acetaminophen), and DMARDs, can result in anemia. There is much debate among experts, but one idea is that “drugs can form complexes with proteins and red blood cells, and the body sees this entire entity as a ‘foreigner’ and targets and removes it — therefore leading to anemia,” says Dr. Jalloh. Frequent blood testing may be used to monitor anemia risk.

NSAIDs can also cause edema, which is swelling caused by a build-up of swelling in the body’s tissues. These drugs may cause edema in a variety of ways, but the one that researchers have studied the most is kidney damage that can result from the use of such medications. “When the kidneys don’t work as well, less fluid is removed from the body and the excess fluid may accumulate within the body as a result,” he explains.

For the millions of people living with arthritis, there are several types of medication that can relieve the symptoms and protect the joints. With a healthy dose of awareness and clear communication with your healthcare provider, you can reap the benefits of these medications while reducing the risks of the various side effects they can cause.

5 Pro Tips

Dr. Jalloh offers the following tips to help people with arthritis minimize the risk of these side effects, and how to deal with them if you think you might be affected.

  1. Have a discussion with your health care provider or pharmacist to weigh the risks and benefits of a particular drug, in light of the side effects associated with it.
  2. You may also have a medication check-up with your pharmacist to review the medications you are taking. He or she may be able to recommend which ones should be discontinued or switched to alternatives to lower the risk of side effects.
  3. The most common way to minimize or avoid side effects is to lower the dose of the medication.
  4. Other possible solutions include taking the drug fewer times per day, taking it at certain times of day, and taking it with food.
  5. These steps should only be taken with the guidance of your doctor, however, especially with inflammatory forms of arthritis. Abruptly stopping a medication or cutting the dose on your own can lead to serious risks, including further damage to the joints and other organs.

Rheumatoid Arthritis Medication Guide

Biologic Drugs

  • How biologic drugs work: These agents inhibit key factors responsible for inflammatory responses in the immune system. Abatacept inhibits T-cell activation. Etanercept, infliximab, golimumab, certolizumab and adalimumab are tumor necrosis factor (TNF) antagonists. Tocilizumab blocks interleukin-6 (IL-6), rituximab inhibits B-cells and anakinra inhibits interleukin-1 (IL-1).

Abatacept (Orencia)

  • Who should not use this medication: People with allergy to abatacept or those with severe infection should not take this medication.
  • Use: Abatacept is given intravenously (IV) as an infusion over 30 minutes. During the first month, it is given every two weeks, then every four weeks thereafter. It may be used alone or with DMARDs. Orencia is also given as a weekly subcutaneous injection.
  • Drug or food interactions: Abatacept should not be administered if TNF antagonists, such as etanercept, infliximab, or adalimumab, are also being given to treat rheumatoid arthritis. Combining these therapies greatly increases the risk for serious infection. Additionally, it should not be given with anakinra since this combination has not been studied adequately.
  • Side effects: If serious infection occurs, abatacept should be discontinued. Abatacept must be used with caution in individuals with chronic obstructive lung disease (COPD) since these individuals are more likely to develop side effects that exacerbate their COPD. Common side effects include the following:
    • Headache
    • Upper respiratory tract infection
    • Sore throat
    • Nausea

Etanercept (Enbrel)

  • Who should not use this medication: People with allergy to etanercept and those with serious infection or active tuberculosis should not take the drug.
  • Use: Etanercept is taken as an injection once or twice a week. It may be used alone or with concomitant therapy such as methotrexate.
  • Drug or food interactions: Etanercept may increase infection risk or decrease blood cell counts when used with other immune modulators or immunosuppressant drugs (for example, anticancer agents or corticosteroids). Immunization with some vaccines may not be effective.
  • Side effects: Etanercept must be used with caution in people with heart failure or impaired kidney function. If a serious infection develops, the drug must be discontinued. Exacerbation of tuberculosis and the development of drug-induced lupus are other possible side effects. The following adverse effects are possible:
    • Injection site pain, redness, and swelling
    • Fever
    • Rash
    • Cold or flu symptoms
    • Stomach upset
    • Nausea
    • Vomiting

Infliximab (Remicade)

  • Who should not use this medication: People who have moderate to severe heart failure should not take doses greater than 5 mg/kg (of body weight). Those with allergy to infliximab or mouse protein should not take the drug. Patients with active infection, including tuberculosis, should not use the drug.
  • Use: Infliximab is given as a two-hour intravenous infusion in a doctor’s office. Initially, three doses are given within a six-week period; thereafter, a single dose is given every eight weeks to maintain the drug’s effect. The interval between doses is shortened if the eight-week regimen fails to control symptoms. It is most often used with concomitant methotrexate.
  • Drug or food interactions: Use of other immunosuppressant drugs increases the risk for infection.
  • Side effects: Infliximab may increase the risk of infection, particularly when other immunosuppressant drugs are used concurrently. People with heart failure may experience worsening of heart disease. Infliximab may exacerbate tuberculosis and drug-induced lupus. Symptoms could include fever, rash, headache, or muscle aches three to 12 days after infusion. The body may eventually produce antibodies toward infliximab, thereby decreasing the drug’s effectiveness.

Golimumab (Simponi and Simponi Aria)

  • Who should not use this medication: People with allergy to golimumab must not use it. Treatment must not be started if an active infection is present.
  • Use: Golimumab (Simponi) is given as an injection every month. Simponi Aria is the intravenous formulation of golimumab and is given intravenously every four weeks initially, and then every eight weeks. It is most often used with concomitant methotrexate.
  • Drug or food interactions: Clinical investigators are studying whether other immunosuppressant drugs increase the risk for infection if administered with golimumab.
  • Side effects: Golimumab must be used with caution in people with a history of nervous system disorders or heart disease. Golimumab may cause exacerbation of tuberculosis and drug-induced lupus. Call a doctor if symptoms of lung or sinus infection (for example, fever, cough, sinus pressure, or headache) develop.

Certolizumab Pegol (Cimzia)

  • Who should not use this medication: People with allergy to certolizumab must not use it. Treatment must not be started if an active infection is present.
  • Use: Certolizumab is given as an injection every other week or monthly. It can be self-administered at home or administered in a doctor’s office.
  • Drug or food interactions: Clinical investigators are studying whether other immunosuppressant drugs increase the risk for infection if administered with certolizumab.
  • Side effects: Certolizumab must be used with caution in people with a history of nervous system disorders or heart disease. Certolizumab may cause exacerbation of tuberculosis and drug-induced lupus. Call a doctor if symptoms of lung or sinus infection (for example, fever, cough, sinus pressure, or headache) develop.

Adalimumab (Humira)

  • Who should not use this medication: People with allergy to adalimumab must not use it. Treatment must not be started if an active infection is present.
  • Use: Adalimumab is given as an injection every other week (or sometimes weekly). It is most often used with concomitant methotrexate.
  • Drug or food interactions: Clinical investigators are studying whether other immunosuppressant drugs increase the risk for infection if administered with adalimumab.
  • Side effects: Adalimumab must be used with caution in people with a history of mouse protein allergy, nervous system disorders, or heart disease. Adalimumab may increase blood pressure or cause heart rhythm abnormalities. Adalimumab may cause exacerbation of tuberculosis and drug-induced lupus. Call a doctor if symptoms of lung or sinus infection (for example, fever, cough, sinus pressure or headache) develop.

Tocilizumab (Actemra)

  • Who should not use this medication: Do not take tocilizumab if you are allergic to it or any of its ingredients.
  • Use: Tocilizumab is given as a monthly intravenous infusion or subcutaneous weekly injection.
  • Drug or food interactions: The risk of serious infections (for example, pneumonia) may increase if tocilizumab is taken with other biologic medications.
  • Side effects: Call a doctor if any of the following occur:
    • Itching
    • Rash
    • Fever
    • Chills
    • Sore throat
    • Joint pain or swelling
    • Sores or white patches in the mouth or throat

Sarilumab (Kevzara)

  • Who should not use this medication: Do not take sarilumab if you are allergic to it or any of its ingredients.
  • Use: Sarilumab is given as a monthly intravenous infusion or subcutaneous weekly injection.
  • Drug or food interactions: The risk of serious infections (for example, pneumonia) may increase if sarilumab is taken with other biologic medications.
  • Side effects: Call a doctor if any of the following occur:
    • Itching
    • Rash
    • Fever
    • Chills
    • Sore throat
    • Joint pain or swelling
    • Sores or white patches in the mouth or throat

Rituximab (Rituxan)

  • Who should not use this medication: Those with allergy to rituximab should not take the drug. Patients with active infection, including tuberculosis, should not use the drug.
  • Use: Rituximab is given as a four-hour intravenous infusion in a doctor’s office twice two weeks apart every six months.
  • Drug or food interactions: Use of other immunosuppressant drugs is possible but increases the risk for infection.
  • Side effects: Rituximab may increase the risk of infection, particularly when other immunosuppressant drugs are used concurrently. Rituximab may exacerbate tuberculosis and drug-induced lupus. Symptoms could include fever, rash, headache, or muscle aches during or after infusion.

Anakinra (Kineret)

This biologic medication is generally reserved for a specific type of rheumatoid disease in children called systemic onset juvenile inflammatory arthritis.

  • Who should not use this medication: People with allergy to anakinra or Escherichia coli-derived proteins should not take anakinra. Treatment must not be started if an active infection is present.
  • Use: Anakinra is taken as a daily injection at approximately the same time each day.
  • Drug or food interactions: The risk of serious infections (for example, pneumonia) may increase if anakinra is taken with tumor necrosis factor antagonists such as etanercept (Enbrel), adalimumab (Humira), or infliximab (Remicade). Anakinra does not cause drug-induced lupus.
  • Side effects: Common adverse effects include nausea, diarrhea, or abdominal pain. Call a doctor if any of the following occur:
    • Itching
    • Rash
    • Fever
    • Chills
    • Sore throat
    • Joint pain or swelling
    • Sores or white patches in the mouth or throat

Question: After reading the pharmacy sheets listing side effects of the medications I take for rheumatoid arthritis (RA), I can’t help but wonder if the “cure” is worse than the disease. Is it possible I’d be better off skipping the medications and taking my chances with the RA?
Answer: For those with arthritis, side effects of medication are an understandable worry. But I would hate to see fear cause you to give up medications completely. The dangers of untreated RA, psoriatic arthritis, lupus or other inflammatory diseases far outweigh the risks of the drugs used to treat it in most cases. 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.
The pharmacy sheets are provided as a service to make you aware of side effects that can occur with a certain medication. Keep in mind that the key word here is “can.” You shouldn’t assume that the listed side effects will necessarily occur in you. Even if you do experience one or more side effect, you may be able to reverse or halt them by stopping or changing medications. In many cases, no action is needed; the side effects resolve on their own.
Sometimes we have to risk experiencing a side effect to gain a medication’s benefits. 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.
There are also several things you can do to reduce your risk of drug side effects. Here are a few:

  • Other medications. Let your doctor know about any other medications you are taking – even over-the-counter ones – because some can add to the side effects of others. For example, taking aspirin along with a prescription nonsteroidal anti-inflammatory drug (NSAID) can increase your risk of stomach problems.
  • Supplements. Nutritional supplements can affect the way a drug – such as taking folic acid along with methotrexate. Vitamin supplements can reduce the risk of certain side effects. In other cases, supplements can interfere with the action of a medication or even enhance its potential side effects.
  • Foods. Find out if there are certain foods you should eat or avoid while taking a medication. Most drugs, including NSAIDs, should be taken with food to reduce the risk of stomach upset. For others, such as minocycline, taking with food can decrease the drug’s absorption.
  • Alcohol. Forgo alcohol – it can add to the side effects of most drugs, from analgesics to antidepressants. If you can’t or don’t want to give up alcohol altogether, set a limit of two drinks (including beer) per week.
  • Dosage. Ask your doctor to prescribe the lowest beneficial dose of a drug and never take more than the prescribed amount. Many side effects are related to dosage.
  • Timing. Take the drug at the time designated by your doctor. Timing, in some cases, can influence a drug’s side effects. For example, taking the osteoporosis drug alendronate when you get up in the morning, rather than before lying down at night, can cut the risk of esophageal ulcers.
  • Consistency. Never stop taking any medication without consulting your doctor. A drug can’t help you if you don’t take it, but abruptly stopping a drug can hurt you. Drugs such as prednisone, for example, must be tapered slowly to avoid serious adverse effects.
  • Communicate. Let your doctor know if you suspect a side effect. He can determine whether the side effect requires treatment, discontinuation or dosage reduction.

Leonard H. Calabrese, DO
Department of Rheumatologic and Immunologic Disease
Cleveland Clinic
Cleveland, Ohio

Patients’ 9 Biggest Concerns About Rheumatoid Arthritis Medication Side Effects

Taking medication for any condition carries some risks, but information is power. Here is the information you need to make sense of potential side effects so you can balance them against the benefits of treating your rheumatoid arthritis (RA).

Read more here about what every RA patient should know about drug side effects, as well as get a checklist of questions to ask your doctor any time you start a new RA medication.

1. My medication came with an insert that includes a long list of side effects. Am I guaranteed to have one or more of them?

Not at all. Drug manufacturers are required to tell you about all those potential side effects, but there’s a less than 10 percent chance that an individual patient will experience a side effect of any FDA-approved drug, says Kathryn Dao, MD, associate director of clinical rheumatology at Baylor Research Institute in Dallas, Texas.

The chance that you’ll experience a serious side effect — such as an infection that requires being hospitalized — is even lower: less than 5 percent.

2. Is there anything I can do to lower my risk further?

Yes. It starts by picking the right drug, which means working with your doctor to choose the option that you both think will work best for your RA and will be the safest, given any other conditions and risk factors you might have, says Kevin Winthrop, MD, a professor of infectious diseases and public health at Oregon Health & Science University in Portland. Also key: If you take methotrexate, as many RA patients do, pairing it with a folic acid supplement can help counter many of its side effects, says Dr. Dao.

3. What if I’m especially concerned about a specific side effect?

Tell your doctor. There are many RA treatments to choose from. Each drug has a different side effect profile. Tell your doctor what’s on your mind and they can help you choose a medication that’s less likely to cause the problem you’re worried about, says Dr. Withrop.

4. I heard methotrexate is a chemotherapy drug. Doesn’t that mean it’s toxic?

Methotrexate is, in fact, sometimes used to treat cancer — but “the dose makes the poison.” Cancer patients typically take 100 to 300 mg of methotrexate, says Dr. Dao; people with RA are usually prescribed 10 to 25 mg a week. This means that the side effects of methotrexate are much different for treating RA than they are for cancer.

5. Many RA drugs raise the risk of infection. How worried should I be about this?

Serious infections do happen. This is because RA drugs work on the immune system to reduce inflammation, which can also make you more susceptible to infections. With certain RA drugs, your doctor will test you for inactive tuberculosis (TB) and treat that first if you have it. That said, most patients who take RA drugs that suppress the immune system only end up with a few more minor infections like colds or urinary tract infections, says Dr. Dao.

Here’s more information on other tests you should get before starting a biologic for RA.

6. Are biologics more apt to cause side effects than other types of RA drugs?

No. Some biologic drugs, including TNF inhibitors, are considered “safer” than methotrexate, which is not a biologic,, says Dr. Dao, who adds that pregnant women can use TNF inhibitors but cannot take methotrexate. Long-term use of corticosteroid medication, like prednisone, also generally confers a greater risk of side effects than do biologic drugs. “Biologic” just means that a drug is made from a natural source (animal or human protein) rather than from a synthetic compound.

7. If I develop side effects after agreeing to take a drug, can I stop?

Of course — you’re not signing a long-term contract. That said, your doctor may advise you to wait a certain period of time to see how you adjust to a new drug before making any changes. You should also know that certain medications can take a while to get out of your system. After starting rituximab, for instance, it can remain in your body for up to a year. And some drugs, like prednisone, need to be tapered off slowly.

Never stop a drug without first talking to your doctor.

8. Why do new side effects sometimes come to light after a drug has been approved by the Food and Drug Administration (FDA)? Shouldn’t these have been sorted out earlier?

Clinical trials leading up to FDA approval yield a lot of information about drug efficacy and safety (including possible side effects), but they’re done on a relatively small group of patients compared to how many people end up using these drugs after they hit the market, says Barbara Young, PharmD, editor of consumer medication information at the American Society of Health-System Pharmacists. Adverse events may be reported by patients and doctors after a drug is out for some time; sometimes drug manufacturers also conduct post-marketing studies that lead to new information about side effects.

9. Where can I find more information about a drug I’m taking?

Your doctor or pharmacist is always a good place to start, as is the drug manufacturer’s website. You can also search the FDA’s Medication Guide Database or consult safemedication.com.

Keep Reading

  • Tips to Help You Remember to Take Your Arthritis Medications
  • What to Do Any Time You Start a New Medication for Arthritis
  • Signs to Consider Switching Your Arthritis Medication

This article is part of a Patient’s Guide to Understanding RA Drug Side Effects and was made possible by a grant from Sanofi Genzyme.

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