Is the new rheumatoid arthritis medication right for you?

Although it’s impossible to know whether a new rheumatoid arthritis medication will squelch your RA symptoms, you can better predict its effect on you by knowing whether it has helped similar RA patients. Clinical studies show that a given new rheumatoid arthritis medication reduces symptoms or disease progress in only some RA patients. Some RA patients may improve dramatically while others do not improve. Some patients may even get worse.

Clinicians usually compare the health of RA patients on the new rheumatoid arthritis medication to those patients taking a placebo (a look alike pill) or a commonly prescribed set of medications. They note any improvement or worsing of RA symptoms such as joint swelling, pain, various blood markers (ESR, CRP, anti-CCP, RF), and quality of life based on health assessment questionnaire.

Clinical trials also describe the side effects that occur in their patient population. Further monitoring after FDA approval usually identifies additional side effects. For example, further testing of Vioxx indicated that it increased the risk of heart attack in RA patients taking it for more than 18 months.

Sometimes I felt like one of my previous physicians prescribed a new rheumatoid arthritis medication based on a “what to try list” rather than on my individual disease symptoms and progression.

If you don’t respond with medication A, then let’s try medication B. Then medication C, then D. Sometimes several medications are prescribed together.

Once, I took the benefits from a common RA medication on faith in my doctor. He guaranteed that I would feel wonderful within a week-- Full of energy, no pain, clear thinking, have a lively step, etc.

I only felt better for 18 hrs so he was partially right.

Then my joints began exploding with at least 20 grenades and excruciating pain. I became physically exhausted…only could sleep a lot, eat a little, hobble slowly with heavy breathing. My concentration for work plummeted. Within 3 days, I had to call and cancel medication.

It took many months, years to rebuild my body’s health.

He meant well. The medication prescribed has shown benefit in many RA patients.

However, that medication did not boost my health for any appreciable time. This incident spurred me to develop a list of 10 questions to ask before taking any medication. Like me, you’ll likely respond better when your healthcare practitioner addresses your current health profile rather than prescribing from a list.

If you and your doctor have found a medicine or drug combination that helps you achieve remission with medication, then continue it under the physician's care. Be very thankful as many RA patients have not achieved this goal.

However, if you're still in a lot of pain and stiffness, then you may want to consider these additional perspectives.

What benefits will this new rheumatoid arthritis medication likely provide you? What are the risks?

Often, your physicians’ answers to these 2 questions are very general—for all RA patients.

Here are 10 easy questions to ask your doctor or healthcare provider so you more fully grasp the potential risks and likely benefits for your RA today.

Then, you with your healthcare team can decide whether you’ll likely gain a major benefit from taking the new rheumatoid arthritis medication.

I learned these questions the hard way—don’t let it happen to you.

Here’s a review of RA medications list derived from the NIAID website on RA.

RA medications: pain relievers, inhibitors of inflammation, steroids, DMARDs and biological response modifiers, antibiotics.

Each old or new rheumatoid arthritis medication exerts its effects at one or more points in the disease process of RA.

Analgesics: Pain relievers

Analgesics relieve pain.

Aspirin (Buffered or Plain) is a very popular pain reliever. It’s side effects include upset stomach; tendency to bruise easily; ulcers, pain, or discomfort; diarrhea; headache; heartburn or indigestion; nausea or vomiting. Doctor monitoring is needed.

Acetaminophen are found in many nonprescription medications such as aspirin-free Anacin*, Excedrin caplets, Panadol, Tylenol, and Tylenol Arthritis. Patients usually have no visible side effects when taken as directed for short periods.

Maximum dose recommended is 4 grams daily. However, liver enzyme tests indicate that 4 grams acetaminophen can begin to raise liver enzyme, indicating liver stress. A safer dosage is 2-3 g / day.

Please be aware that as many as 14,000 people suffer from an overdosage of acetaminophen yearly, according to a 2003 FDA review.

Acetaminophen overdose induces liver toxicity and liver failure, providing 50% of patients getting a liver transplant in 2003.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

NSAIDs are a large class of pharmaceutical medications useful against pain and inflammation. Most inhibit the cycloxygenase (COX) 1 and 2 enzymes. While they are not a new rheumatoid arthritis medication, they are often prescribed.

Three main NSAIDS are Ibuprofen, Ketoprofen, and Naproxen. They are the active ingredient in many over the counter medications.

NSAIDs help relieve pain within hours of administration in dosages available over-the counter (available for all three medications). They relieve pain and inflammation in dosages available in prescription form (ibuprofen and ketoprofen). It may take several days to reduce inflammation.

NSAIDs can cause stomach irritation or, less often, can affect kidney function. The longer a person uses NSAIDs, the more likely he or she is to have side effects, ranging from mild to serious. Many other drugs cannot be taken when a patient is being treated with NSAIDs because they alter the way the body uses or eliminates these other drugs.

NSAIDs sometimes are associated with serious gastrointestinal problems, including ulcers, bleeding, and perforation of the stomach or intestine. (Perforation of the intestines is called leaky gut syndrome.) People over age 65 and those with any history of ulcers or gastrointestinal bleeding should use caution before taking NSAIDs.

More than a dozen others – including a subclass called COX-2 inhibitors – are available only with a prescription.

COX-2 inhibitors have recently been shown to exhibit higher cardiovascular risk. Vioxx was removed from the market.

NSAIDS are known to hinder the healing of abrasions on the cartilage in the joints.

Corticosteroids:

Methylprednisolone, prednisone, cortisone are commonly prescribed corticosteroids.

Methylprednisolone, and prednisone are available in pill form or as an injection into a joint. Improvements are usually seen in several hours up to 24 hours after administration. There is potential for serious side effects, especially at high doses.

They are used for severe RA flares and when the disease does not respond to NSAIDs and DMARDs.

From personal experience, they are contraindicated for treatment of patients with joint infection(s).

Side effects include increased appetite, indigestion, nervousness, or restlessness. Side effects of methylprednisolone, and prednisone also include osteoporosis, mood changes, fragile skin, easy bruising, fluid retention, weight gain, muscle weakness, onset or worsening of diabetes, cataracts, increased risk of infection, hypertension (high blood pressure).

For all corticosteroids, let your doctor know if you have one of the following: fungal infection, history of tuberculosis, underactive thyroid, herpes simplex of the eye, high blood pressure, osteoporosis, or stomach ulcer.

Disease-modifying antirheumatic drugs (DMARDs)

DMARDs often take several months to begin to reduce RA symptoms.

Azathioprine was first used in higher doses in cancer chemotherapy and organ transplantation. It is used in patients who have not responded to other drugs, and in combination therapy.

Azathioprine inhibits purine synthesis in growing cells, including leukocytes and lymphocytes.

Azathioprine’s side effects include cough or hoarseness, fever or chills, loss of appetite, lower back or side pain, nausea or vomiting, painful or difficult urination, unusual tiredness or weakness. Most serious side effect is bone marrow suppression.

Before taking this drug, tell your doctor if you use allopurinol or have kidney or liver disease. This drug can reduce your ability to fight infection, so call your doctor immediately if you develop chills, fever, or a cough. Regular blood and liver function tests are needed.

Cyclosporine was first used in organ transplantation to prevent rejection. It is used in patients who have not responded to other drugs.

Cyclosporine inhibits the activation and growth of cells of the immune system (T cells).

Side effects of cyclosporine include bleeding, tender, or enlarged gums; high blood pressure; increase in hair growth; kidney problems; trembling and shaking of hands.

Before taking this drug, tell your doctor if you have one of the following: sensitivity to castor oil (if receiving the drug by injection), liver or kidney disease, active infection, or high blood pressure.

Using this drug may make you more susceptible to infection and certain cancers. Do not take live vaccines while on this drug.

Gold sodium thiomalate was one of the first DMARDs used to treat rheumatoid arthritis. A higher response rate is observed in recent onset RA. Significant toxicity often occurs within 5 years.

Side effects include redness or soreness of tongue; swelling or bleeding gums; skin rash or itching; ulcers or sores on lips, mouth, or throat; irritation on tongue. Joint pain may occur for one or two days after injection.

Before taking this drug, tell your doctor if you have any of the following: lupus, skin rash, kidney disease, or colitis. Periodic urine and blood tests are needed to check for side effects.

Hydroxychloroquine is also used to treat malaria.

Side effects include diarrhea, eye problems (rare), headache, loss of appetite, nausea or vomiting, stomach cramps or pain.

Doctor monitoring is important, particularly if you have an allergy to any antimalarial drug or a retinal abnormality.

Leflunomide suppresses the immune response by inhibiting pyrimidine synthesis.

Side effects of leflunomide include bloody or cloudy urine; congestion in chest; cough; diarrhea; difficult, burning, or painful urination or breathing; fever; hair loss; headache; heartburn; loss of appetite; nausea and/or vomiting; skin rash; stomach pain; sneezing; and sore throat.

Before taking this medication, let your doctor know if you have one of the following: active infection, liver disease, known immune deficiency, renal insufficiency, or underlying malignancy. You will need regular blood tests, including liver function tests.

Leflunomide must not be taken during pregnancy because it may cause birth defects in humans.

Methotrexate was originally used in chemotherapy for cancer. It is taken orally or by injection. Methotrexate often results in rapid improvement although it usually takes 3-6 weeks to begin working.

At doses commonly used in RA treatment, methotrexate inhibits purine metabolism, T cell activation.

Side effects include abdominal discomfort, chest pain, chills, nausea, mouth sores, painful urination, sore throat, unusual tiredness or weakness.

Doctor monitoring is important, particularly if you have an abnormal blood count, liver or lung disease, alcoholism, immune-system deficiency, or active infection.

Methotrexate must not be taken during pregnancy because it may cause birth defects in humans.

Sulfasalazine is thought to suppress the immune response.

It is poorly absorbed. One of its main benefits may be to suppress ulceratis colitis which may be causing the arthritis.

Side effects include abdominal pain, aching joints, diarrhea, headache, sensitivity to sunlight, loss of appetite, nausea or vomiting, skin rash.

Doctor monitoring is important, particularly if you are allergic to sulfa drugs or aspirin, or if you have a kidney, liver, or blood disease.

Biologic Response Modifiers

These new medications for rheumatoid arthritis selectively block parts of the immune system called cytokines. Cytokines play a role in inflammation. Long-term efficacy and safety are uncertain.

The side effects of biological response modifiers include increased risk of infection, especially tuberculosis. Also Increased risk of pneumonia, and listeriosis (a foodborne illness caused by the bacterium Listeria monocytogenes). Some studies observe a higher risk for lymphoma.

Inhibitors of Tumor Necrosis Factor (TNF) alpha:

Tumor necrosis factor alpha is involved in several pathways of RA disease:

TNF alpha feeds the flames of inflammation which involves recruitment of white blood cells and usually helps heal diseased tissues. Chronic inflammation is thought to lead to RA progression.

TNF alpha increases angiogenesis is the process of making more blood cells or expanding pannus.

TNF alpha boosts bone resorption is needed to replace weak bone matrix by stimulating osteoclasts activity.

TNF alpha also increases production of matrix metalloproteinases, enzymes involve in dissolving .

Three biological response modifiers currently approved by FDA are Etanercept, Infliximab and Adalimumab.

Response rates of 18% to 70% were observed {Klotz, 2007 #744} {Mori, 2007 #748} {Hyrich, 2006 #751}.

Patients with a high level of disability had a lower response rate {Symmons, 2006 #752}. A better response was associated with the current use of methotrexate (MTX) {Hyrich, 2006 #751}.

According to a recent survey of rheumatologists, over 94% of rheumatologists reported switching patients from one TNF inhibitor to a different TNF inhibitor due to inadequate response or side effects {Kamal, 2006 #749}.

Etanercept is a genetically engineered soluble tumor necrosis factor (TNF) receptor. It binds both TNF alpha and lymphotoxin alpha. It blocks much of your body’s TNF alpha and lymphotoxin from binding to its target cells.

Side effects of Etanercept include pain or burning in throat; redness, itching, pain, and/or swelling at injection site; runny or stuffy nose, serious skin and soft tissue infections {Salliot, 2007 #750} {Dixon, 2006 #514}.

A rare side effect is the development of a multiple sclerosis-like symptoms or demyelination. Usually stopping the medication allows the nerves to heal.

Infliximab and Adalimumab are genetically engineered antibodies that bind tumor necrosis factor alpha. They block much of your body’s TNF alpha from binding to its target cells.

Response rates of 18% to 70% were observed {Klotz, 2007 #744} {Mori, 2007 #748} {Hyrich, 2006 #751}.

These medications are often prescribed for RA patients with an inadequate response to DMARDs. They may be prescribed in combination with some DMARDs, particularly methotrexate.

Side effects of Infliximab include abdominal pain, cough, dizziness, fainting, headache, muscle pain, runny nose, shortness of breath, sore throat, vomiting, wheezing, serious skin and soft tissue infections {Salliot, 2007 #750} {Dixon, 2006 #514}. A rare side effect is the development of a multiple sclerosis-like symptoms or demyelination.

Side effects of Adalimumab include redness, rash, swelling, itching, bruising, sinus infection, headache, nausea, serious skin and soft tissue infections {Salliot, 2007 #750} {Dixon, 2006 #514}. A rare side effect is the development of a multiple sclerosis-like symptoms or demyelination. It can usually be reversed by stopping the medication.

Interleukin1 Inhibitor

Anakinra requires daily injections. Long-term efficacy and safety are uncertain.

Interleukin-1 is involved in inflammation, recruitment of neutrophils, activation of immune cells, stimulation of MMPs, increased cartilage resorption, pannus formation.

Side effects of Anakinra include redness, swelling, bruising, or pain at the site of injection; head-ache; upset stomach; diarrhea; runny nose; and stomach pain.

A rare side effect is the development of a multiple sclerosis-like symptoms or demyelination. It can usually be reversed by stopping the medication.

Antibiotics

Tetracyclines including minocycline have shown promising results in treating some RA patients.

Minocycline exhibits anti-bacterial activity. It inhibits inflammatory activity via suppression of matrix metalloproteinases, and suppresses chemotaxis, lymphocyte growth.

Minocycline treatment of RA patients has induced “clinically significant improvement in disease activity with no absolute increased risk of side effects.” {Stone, 2003 #676}. Several clinical practices have observed significant remission rates with the treatment with tetracycline based antibiotics such as minocycline {Stone, 2003 #676}.

Minocycline side effects include pigmentation, nausea, dizziness, skin rash, headaches, interstitial nephritis, acute hepatic injury, lupus like syndrome, light sensitivity, and dermatitis.

Please note: If antibiotic treatment causes a worsening of symptoms, it’s likely your body has been overwhelmed with killed bacteria and is clearing them. After your body has cleared the killed bacteria, then your symptoms and disease course can greatly improve. Patients who worsen early have been the higher long term responders, many going into remission.

Summary

There are many old and new rheumatoid arthritis medications. They each have their mode of action and they each improve the symptoms of RA in some patients.

They all also pose risks to the RA patients.

Choosing a treatment is about weighing the risks and benefits so that you get more benefits than the risks taken. Many drugs require monitoring of the patient to quickly identify whether you get a major side effect.

RA patients who actively participate in their own healthcare choices have less pain and disease progression.

Carefully evaluating the chances of any RA treatment for improvement and worsening of symptoms of your RA type before accepting a new treatment will likely smooth your RA journey.

Comparing the answers to these 10 questions while consulting with your healthcare practitioner(s) have helped me choose the most healing strategies for my RA.

In addition, if you begin taking a specific treatment, monitoring your progress (improvement, status quo, deterioration) can help you decide whether this treatment is helping.

Please note that some treatments, such as antibiotic treatment, cause a worsening of symptoms while your body clears the killed bacteria. After your body has cleared the killed bacteria, then your symptoms and disease course can greatly improve.

Wishing you much healing!