Juvenile rheumatoid arthritis is a chronic illness for which there is not yet a cure. Fortunately, many medications today reduce the inflammation, pain and stiffness associated with the illness, while minimizing permanent joint damage. Some meds dramatically slow down the advancement of the arthritis, and may even stop it in its tracks, leading to permanent remission. Your child’s pediatric rheumatologist will design a specific medication program, with the fewest side effects, to control the JRA.

When your child’s doctor prescribes a medication program, there are five  questions to ask.
 
1. What does the medication do?
2. How and when should my child take it?
3. How long will my child need to use it?
4. Should my child avoid any other medicines, drinks, foods, or activities while taking this one?
5. What are the possible risks and side effects of each medication, and what should I do if my child does have an adverse effect?

It is important to understand that whatever medication program is designed by the doctor, the meds must be taken regularly and exactly as prescribed to be fully effective.

Nonsteroidal anti-inflammatory drugs (NSAIDs), also known as pain killers

NSAIDs (en-seds) are often the first level of medications prescribed to treat symptoms of juvenile rheumatoid arthritis.

NSAIDs, nonsteroidal, anti-inflammatory medications, generally available over-the-counter, have analgesic (an-nal-jeez-ik), to reduce pain, antipyretic (an-ti-py-ret-ic), to reduce fever, and anti-inflammatory, to reduce swelling, properties. They often allow your child to participate in normal day-to-day activities. NSAIDs do not cause addiction, can generally be taken over a long
period of time, and are usually taken by mouth in liquid or tablet form.

If your child has mild arthritis, an NSAID may be the only medicine he or she needs. Often, one NSAID works while another does not, and it may be necessary to try several to find which one(s) works best for your child.

In contrast, stronger medicines, such as the opiates Codeine and Tramadol, which are not prescribed for JRA, are centrally acting analgesics, prescribed for moderate to severe pain. They can cause side effects as nausea, vomiting, drowsiness, constipation, and in rare circumstances, breathing difficulties.

Paracetamol (par-a-cet-a-mol), an acetaminophen (a-seet-a-min-oh-fen), also known as Tylenol®, in liquid or tablets, is prescribed for temporary relief of mild levels of pain. Calpol, also a paracetemol, not available in the United States at this time, is sold in the UK, Ireland, India and Cyprus.

Ibuprofen (i-byu-pro-fen), Motrin®, Advil®, Nuprin®, has been available over-the-counter since 1985 to reduce inflammation, ease mild to moderate pain and reduce fever.

Naproxen (na-prok-sen) sodium, often sold under the brand name Aleve®, is among the most frequently prescribed of NSAIDs, based on its low incidence of side effects and its effectiveness for treatment of juvenile rheumatoid arthritis.

Celebrex® was approved by the FDA in December 2006 for the relief of signs and symptoms of JRA in patients two years of age and older. Celebrex® is a Cox-2 (an enzyme that makes prostaglandins that cause inflammation and pain and fever) inhibitor. It is advised that Celebrex(® be used with caution in children with systemic onset JRA, due to the risk for serious adverse reactions. Celebrex® is the only Cox-2 inhibitor available in the U.S., while the similar medications, etoricoxib, Arcoxia® and lumiracoxib, Prexige®, are available in other
countries.

Arthrotec® (are-throw-teck) is a combination of diclofenac (dye-kloe-fen-ak), and misoprostol (mye-soe-prost-ole). Diclofenac is an NSAID, similar to ibuprofen, naproxen and others. Diclofenac inhibits the production of prostaglandins that promote inflammation, pain, and fever by blocking both Cox-1 (a protein that acts as an enzyme to speed up the production of certain chemical messengers, called prostaglandins, within the stomach) and Cox-2 enzymes.
Misoprostol is a synthetic prostaglandin that stimulates secretion of mucus in the gastrointestinal tract. Mucus protects the lining of the stomach from acid. Misoprostol has been shown to reduce the frequency of ulcers of the stomach caused by NSAIDs. Arthrotec® was approved by the FDA in December, 1997.

If your child’s doctor prescribes aspirin, it is important to know that it can cause bleeding problems, stomach upset, liver problems, or Reye's syndrome (a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver). Reye’s syndrome is sometimes associated with aspirin consumption by children who have viral diseases such as chicken pox. But for most children, aspirin in the correct dose (measured by blood tests) can control JRA symptoms effectively with few serious side effects.

The NSAID, tolmetin (tole-met-in),Tolectin®, is available with a doctor's prescription. Studies show that this medication is as effective as aspirin with fewer side effects. An upset stomach is the most common complaint, which can frequently be avoided by taking the medication with or after meals.

Other NSAIDs that reduce pain, stiffness and inflammation of the joints include: meloxicam, Mobic®; etodolac, Lodine®; nabumetone, Relafen®; sulindac, Clinoril®; choline magnesium salicylate, Trilasate®, Cataflam®, Voltaren®, Diflusinal and Dolobid®); indomethicin, Indocin®; ketoprofen, Orudis®, Oruvail®), Oxaprozin and Daypro®), and piroxicam.

Side effects?

With NSAIDs, effects may include loss of appetite, constipation, dizziness, confusion, nausea, heartburn, indigestion, tummy pain, and rashes, especially when out in the sun. If your child suffers from wheezing, this symptom may increase. Rarer side effects are mood disturbance and kidney scarring.

When side effects persist, tell your child’s doctor who might prescribe a different medication or change the dosage. Do not give your child more than the recommended dose. 

If symptoms do not respond to the first NSAID, it is appropriate to try a second or third one before moving on to stronger medications. Generally, a medication is used for at least 4 to 6 weeks before switching to another. Some sign of improvement is a good reason to continue with a particular NSAID.
 
Disease-modifying anti-rheumatic drugs (DMARDs)

If NSAIDs do not relieve symptoms of juvenile rheumatoid arthritis, your child’s doctor is likely to prescribe a DMARD (dee-mard), which may be taken in combination with NSAIDs. DMARDs slow down the progress of juvenile rheumatoid arthritis and may even alter the course of the illness, while reducing pain, swelling, and stiffness.

DMARDs act slowly, usually taking weeks or months to take effect. Because they are immunosuppressants, meaning they suppress the immune system (which defendsthe body against infections and disease), your child may become more prone to conditions such as coughs and colds.

Available DMARDs are: methotrexate (me-tho-trex-ate), Rheumatrex®, Trexall®;
sulfasalazine (sul-fa-sal-a-zeen), available generically; hydroxychloroquine (hi-drox-e-klor-o-kwan), Plaquenil ®; and leflunomide, Arava®.
 
Other DMARDs are the T-cell Costimulatory Blocking Agents, including abatacept, Orencia® and the B-cell Depleting Agents, rituximab, Rituxan®, as well as Interleukin-1 (IL-1), receptor antagonist therapy, anakinra Kineret®, Intramuscular Gold, azathioprine, Imuran®, cyclophosphamide, and cyclosporine A, Neoral® and Sandimmune®).
 
Methotrexate

The most commonly-used DMARD is methotrexate, a drug to which more than two-thirds of children respond very well, that has revolutionized the care of children with arthritis. Methotrexate is used to treat active extended oligoarthritis, polyarthritis, systemic arthritis, psoriatic arthritis, enthesitis-related arthritis and uveitis. 

Methotrexate, abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases. It acts by inhibiting the metabolism of folic acid. Methotrexate replaced the more powerful and toxic antifolate aminopterin, and the two should not be confused with each other.

Methotrexate, available for children since the early 1990’s, is taken weekly as a tablet, liquid, or as an injection. When taken as a tablet or liquid (one hour before breakfast, once a week, on the same day of the week), the medication can lead to a feeling of sickness and loss of appetite. Therefore, administration by weekly injections is increasingly used.  Parents are often taught to give these injections, while older children can learn to inject themselves.

Because methotrexate is a slow-acting DMARD, your child may not feel its effects for several weeks. But it is worthwhile to continue using it; research has shown that methotrexate is safe and effective for children with JRA whose symptoms are not relieved by other medications, while long-term side effects rarely occur. Methotrexate is often prescribed with folic acid, a supplement that reduces mouth ulcers and boosts healthy skin.

Side effects?

As with all drugs, methotrexate has side effects. The most common is queasiness or being sick, just after taking the weekly tablet. Although unpleasant, the sickness is not harmful. Many children take the tablet on a Friday night or Saturday to avoid problems during the school week. Other medicines can be taken along with methotrexate to ease the sickness.

Less common side effects are skin rashes, itchy skin, sore mouth, mouth ulcers, mild hair loss, or diarrhea. These side effects will likely go away as your child gets used to the medicine. Because methotrexate can occasionally damage the bone marrow or liver, your child needs regular blood tests, usually done every 2-4 weeks for the first 6 weeks, and then monthly. The tests reveal any risk before damage is done. Unexplained bruising, cough or shortness of breath
should be reported immediately to your doctor. Some young people exhibit sudden mood changes that may be overlooked or dismissed as normal teenagers’ behavior. Discuss any changes or side effects with your doctor.

If your doctor is considering giving your child methotrexate, he or she should not have any 'live' vaccines, including MMR (against measles, mumps and rubella), oral polio, BCG (against tuberculosis) or chicken pox, while taking the drug. Sometimes it is possible to have the vaccinations before starting the medicine, so that your child has protection from these illnesses. Always check with your doctor about vaccines that can be taken safely if your child is on
DMARDs.

Sulfasalazine

This DMARD works well for boys who have enthesitis-related arthritis who carry the HLA-B27 gene. Because sulfasalazine is slow-acting, improvements may only be noticeable after 6 to 8 weeks. Enteric coating on the tablets can reduce nausea.

Side effects?

Side-effects from sulfasalazine include queasiness, headaches and diarrhea. Skin rashes, tummy pain, mouth ulcers and loss of appetite are less common. Sometimes, this drug turns urine orange or dark yellow. If your child develops a skin rash, you should stop administering the drug immediately and contact your child’s doctor. Many of these problems will clear up gradually once the drug is stopped or reduced. When taking sulfasalazine, blood tests are given
periodically.

Careful monitoring for side effects is very important for children taking DMARDs. When side effects are noticed early, the doctor can reduce the dose and eliminate them. Your child might also need blood tests to monitor the effects of these medicines.

Anti-TNF drugs- Biologic agents

Anti-TNF compounds or biologic agents, different kinds of DMARDs, comprise a new class of drugs that block the action of tumor necrosis factor (TNF), a naturally occurring protein in the body that helps instigate inflammation. These genetically engineered products, made from human and animal proteins, were developed in consultation with rheumatologists and first introduced in 1996, as etanercept. They are directed to clock specific immune pathways, such as cyclone signaling, meaning that they block the process of inflammation. Children with polyarticular JRA, in whom other drugs do not work, may be given one of this new class of drug treatments. 

These medications currently include etanercept (eh-ta-ner-cept), Enbrel®, infliximab (in-flix-ih-mab), Remicade® and adalimumab (a-da-lim-yoo-mab), Humira® (with  more biologics in clinical trials) which are administered by regular injections or by infusions into the veins. These very expensive drugs are effective within a few months of use. All three medications are also approved for treatment of psoriatic arthritis and ankylosing spondylitis.

Recently licensed for use with children, pediatric rheumatologists are already seeing dramatic improvement in patients on these drugs. In fact, many children who were unable to participate in normal activities are now on dance and sports teams. The drugs may also provide some cardiovascular protection.

Other important information about biologics include:

• The sooner and more aggressively a child is treated with biologics, the better the effect and the greater the chance of going into remission.

 

• Ten years ago, about 47 percent of kids with JRA still had the illness at age 30. With the “biologic era,” this percentage is expected to decrease.

• Three to four national regulatory bodies are ensuring that clinical studies for these medications are done correctly.

 

• Two biologics are never administered at the same time.

• These medications are not cures. They control the illness.

 

• Studies with biologics suggest that the patient does not build up tolerance to the drug.

• Children on biologics need to have immunizations, as their immune systems are affected by the drugs.

 

• Many researchers agree that the benefits of taking biologics far outweigh the risks.

Side effects

Side effects of biologic agents can include a blocked or runny nose, headache, dizziness, rash, abdominal pain, or indigestion. The meds may also cause itching or swelling where injected. Other side effects include suppression of the immune system, and the possibility of developing serious infections as pneumonia, tuberculosis and cancer (although the biologic/cancer connection is unconfirmed). In spite of these possible side effects, most pediatric rheumatologists agree that the benefits of biologics far outweigh the risks.

Combining drugs
 
Doctors treating children with JRA often find little difference in the effects of administering the conventional synthetic DMARDs, such as methotrexate, leflunomide, and sulfasalazine, with the anti-tumor necrosis factor (anti-TNF) drugs adalimumab, etanercept, and infliximab, when any of these drugs is used alone or as monotherapy,
 
However, combining a conventional DMARD with a biologic often works better than switching to the biologic alone.  According to a systematic review by Katrina E. Donahue, MD, MPH, published online in Annals of Internal Medicine, "Various combinations of biological DMARDs plus methotrexate had better clinical response rates and functional outcomes than monotherapy with either methotrexate or biological DMARDs. In patients previously receiving monotherapy, combination therapy with synthetic DMARDs improved response rates.”

Corticosteroids (cor-ti-co-ste-roids) - often called steroids

Corticosteroids are prescription medications for children with severe juvenile rheumatoid arthritis. They are used as “bridge” therapy to control symptoms until a DMARD takes effect, to prevent complications, such as inflammation of the sac around the heart (pericarditis), and to dampen down a 'flare-up' quickly.

These medicines, generally used for short durations, were over-prescribed in previous years. Steroids can have harmful, long-term side-effects, such as interference with normal growth and increased susceptibility to infection. The most common kind of corticosteroid  is prednisolone (pred-nis-o-lon). Doctors may give this drug to your child by drip (called “methylprednisolone”) if he or she is seriously ill or if other medications are not working. Children with systemic arthritis are sometimes given steroids by drip (in a hospital setting) to reduce a fever quickly.

Local steroid injections into a joint are usually very effective, as they can reduce pain and swelling immediately. This method concentrates the steroid to where it is needed, so that very little of the drug affects the rest of the body and harmful side-effects are minimized. Young children are usually given a light, general anesthetic for joint injections. Older children may have a sedative. The injections may be a bit uncomfortable but should not be painful.

Occasionally, doctors may remove the fluid, which has collected inside a joint, at the same time as injections are given to reduce discomfort. When receiving steroid injections, your child should not have active vaccines including MMR (against measles, mumps and rubella), oral polio, BCG (against tuberculosis) or chicken pox.

Chicken pox can also pose a threat to your child if he or she is on high doses of steroids. If your child is on steroids, it is important that your child’s school notify you when there is an outbreak of chicken pox. Always check with your child’s doctor about vaccines that can be taken safely when on steroids.
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Side effects?

Corticosteroids can interfere with your child's normal growth and can cause thin and/or weakened bones, and increased susceptibility to infections. Some children experience mood changes, including a benign sense of well-being and a boosted appetite. High doses of steroids can also affect blood pressure, diabetic conditions, moods or sleep patterns. Other side effects include easy bruising and a moon-face appearance due to fluid retention and weight gain.

While children are given steroids over long periods, it is dangerous to stop taking them suddenly. Your child should also be given a 'steroid card' if on the meds for any length of time. It is important to have this available if your child is ever seriously ill. Steroids by drip do cause fewer side-effects, but can also cause thinning of bones and a lowered ability to fight infection.

Side effects from steroid joint injections are rare but can include thinning of the tissue under the skin (atrophy) where the injection takes place.

Medications summary

While there are many effective drugs for juvenile rheumatoid arthritis available today, your child may need to try out several different medications, taken alone or in combination with others, to find the one(s) that work best. If one drug does not work immediately, it is important to be patient. The various arthritis medicines and treatments available today are among the most powerful tools to help keep your child with JRA as happy and as well as possible.