How Medication Decisions are Made in RA Treatment

[Guest guest]

How Medication Decisions are Made in RA Treatment

Summary of a presentation at the Living with RA Workshop

A. Paget, MD, FACP, FACR

Physician-in-Chief and Chairman of the Division of Rheumatology

Hospital for Special Surgery

The ph P. Routh Professor of Medicine

Weill Medical College of Cornell University

Research has profoundly changed the treatment of rheumatoid arthritis (RA)

in the past decade on two fronts.

First, we now understand that the " personality " of RA is that is can damage

joints within a few years. This provides a window of opportunity for us to

control the disease. So it's important to make the diagnosis early - and for

the primary care doctor and rheumatologist to work in partnership to start

treatment immediately. Early treatment is particularly important in RA.

Second, new and effective medications for rheumatoid arthritis (RA) are now

available. More are coming to market soon. They have profoundly changed the

treatment of RA. The early use of these medications have made a major dent

in this disorder and what it does to people. Do we have a ways to go? Yes.

Are we much better off than we were in the past? Unbelievably so. So things

have changed.

The Doctor-Patient Relationship: A Partnership

You need to become an informed consumer to work as a partner with your

physician in making decisions about your medications. You need trust and

good communication to make the best decisions. You need to educate yourself,

and your physician needs to educate you. When you have questions, it's your

responsibility to ask them. Constant communication and feedback is vital. An

open relationship and communication are mandatory. If you don't have it, you

should demand it. If you don't get it, you should find it. Decisions must be

made together. You have to be an informed consumer of medical care.

The Process

When I recommend a medication, here's the way I think about it. I'm going to

tell you why I've chosen this medication that I think is best for you. I'll

tell you the facts that we use. And then you tell me whether you think that

they're best for you. You play a big role in the final decision.

When we start on a medication, I assume that, on a scale of 0 to 10 with 10

being the worst, you score a 10 on pain, stiffness, functional limitation,

and fatigue. My goal is that within two months you will be 70% better. My

goal is to bring down the thermostat of inflammation. Every week, I want to

hear from you about how it's working - either by email, fax, phone, or

visits. Is it working? Are there side effects? I will tell you what to

expect and in what time period. If it doesn't work, I will discuss it with

you. I will either change medicines or add medicines.

Facts Used in Making RA Therapeutic Decisions

* Does the patient have RA? Other conditions masquerade as RA - such as

thyroid problems and infections. So the diagnosis must be confirmed.

* How active or severe is the RA? No two people have exactly the same

RA. They have different genetics, different environmental exposures and

triggers. Depending on the severity, you may need a " machine gun " medicine

or a " cruise missile " medicine.

* What is the " personality " of the RA? Again, this relates to your

individual RA and helps the doctor decide what type of medication to use.

* What are the goals of treatment? Although we all want a cure, that's

not here yet. Short of that, there are goals to aim for.

* What medications have already been used? What have you been on before

- at what dose - with what benefit - and what side effects? If you only got

a 3 or 4% improvement, it's not worth the money nor the potential side

effects.

* What medical problems other than RA do you have? These are called

comorbidities. You are not just a disease - you are a whole person. For

example, if you have high blood pressure, your doctor has to make sure not

to give you an arthritis drug that will cause fluid retention and raise your

pressure. If you have a history of ulcers, your doctor will be cautious

about giving you an NSAID - either choosing a COX-2 or adding another drug

to reduce acid output in your stomach. If you have diabetes, that also

affects prescribing. Do you have any allergies?

* What is your age? Children and older adults need different doses.

* What is your insurance coverage? Some health insurers do not cover

certain medications, for example Medicare only covers intravenously injected

medications at this time, not medications injected under the skin.

* What is your capacity to take medication? For example, if you have

hand problems, you may not be able to use some self-injected medications -

so you may need to come to the hospital for that medication or find a friend

or family member to inject you.

The Goals of Therapy in RA in 2003

* Complete remission - This means no evidence of disease (NED), a term

borrowed from oncology (cancer medicine). It does not mean a cure - just

that all the symptoms are gone. That is, complete suppression of:

- joint redness, warmth and swelling (inflammation);

- joint stiffness, particularly in the morning;

- often profound fatigue (pooping out in the middle of the day).

* Back to work and normal function as you know it.

* Avoidance of joint damage and healing of old erosions.

Treatment Options in RA

We have two general classes of drugs - nonsteroidal-anti-inflammatory drugs

(NSAIDs for short, including COX-2s) and disease-modifying anti-rheumatic

drugs (DMARDs for short)

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), including COX-2s

NSAIDs and COX-2s control inflammation and pain, but they can irritate the

intestine, liver and kidney. NSAIDs and COX-2s are not disease-modifying.

The COX-2s, compared to the traditional or older NSAIDs, give you less

gastrointestinal irritation. However, there is no difference in their

anti-inflammatory effectiveness.

* Traditional NSAIDs: aspirin, naproxen (brand-named Naprosyn, Aleve),

ibuprofen (Motrin, Advil, etc.), diclofenac (Voltaren) and many others.

* COX-2s: celecoxib (Celebrex), rofecoxib (Vioxx), valdecoxib (Bextra)

meloxicam (Mobic). (See Guidelines to Help Reduce the Side-Effects of COX-2

Selective Drugs)

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

These drugs have been shown to decrease the development of erosions and

joint-space narrowing and deformities - either significantly or completely.

They vary greatly with regard to side effects and cost.

* methotrexate (Rheumatrex, Trexall)

* leflunomide (Arava)

* sulfasalazine (Azulfidine)

* hydroxychloroquine (Plaquenil)

* etanercept (Enbrel)

* infliximab (Remicade)

* adalimumab (Humira)

* anakinra (Kineret)

Potential Side Effects from RA Medications

This is only a partial list of problems that may arise as side effects from

your medications. Not all people get side effects, and they may vary from

mild to severe. All side effects should be reported to your doctor promptly.

Because of the increased risk of some of these side effects, such as liver

irritation, you will need to have regular blood tests - and you need to know

how often those tests should be done and when to check on those test

results.

* NSAIDs: stomach upset, indigestion, stomach pain, rash, swelling of

the legs due to fluid and salt retention;

* methotrexate: liver irritation, nausea, infections;

* leflunomide: diarrhea, infections, liver irritation;

* sulfasalazine: rash, nausea;

* hydroxychloroquine: rash, diarrhea, eye (retinal) inflammation or

damage (rare);

* etanercept, infliximab, adalimumab: infections, skin rashes at the

site of injections.

Facts to Consider When You Make Final Decisions

* Do I understand:

- what this drug is for?

- how it works?

- how it is monitored?

- how I will know that it is working?

* How do I take the drug:

- by pill, injection, IV?

- daily or weekly? (methotrexate is weekly)

* How much does it cost?

- Does my insurance pay for it?

Studies show that 40 to 50% of people with various types of arthritis don't

take their medication the way the doctor prescribed. People don't want to

take medicine because of side effects, costs and other reasons. But if the

doctor thinks you're taking them and you're not, the doctor makes decisions

thinking you're taking them. And that's not good.

Remember, your doctor needs to know not just about your prescription

medications but also about over-the-counter medications, vitamins, herbals,

alternative therapies, health foods, all of it. Just because you get it in a

health food store doesn't mean it's going to be safe in your situation. For

example, some health food store products can thin your blood; if you take

them with Coumadin, a blood thinner, you can have a problem. So anything you

take, has to be factored into the situation.

Anti-TNF Medications

Tumor Necrosis Factor was discovered here at Hospital for Special Surgery.

Our third surgeon-in-chief realized that lung tumor patients who developed

pneumonia had a decrease in their tumor size. He thought the infection might

be producing a chemical that was shrinking the tumor. That's why the

chemical is called tumor necrosis factor, i.e. a protein that kills

(necroses) tumors.

This TNF protein is made by immune cells in your joints. It's what causes

the inflammation - the redness, warmth and swelling - in your joints and

causes joint damage. It's what make you feels tired. It's what makes you

lose weight.

Over the past few years, we have developed amazing biological medications.

These are the most sophisticated medications that exist today. They actually

block these TNF proteins.

But everything is a balance. TNF not only blocks tumor growth, but it

protects us from infection. Remember the worst flu you ever had? And then

you feel better. One of the factors in your body that helped stop that

infection was TNF. But you do have other warriors in your body to stop

infection. So given how powerful these medicines are in fighting RA, we

accept the fact that you are at higher risk when we block TNF. It's not a

common risk, and we watch you carefully. If you develop an infection - such

as bronchitis or a urinary tract infection - we give you an antibiotic and

stop the anti-TNF medication temporarily until the infection is cured.

Always report fever, chills, night sweats and others signs of infections

such as cough, diarrhea, abdominal pain, and urine symptoms to your doctor

immediately.

Typical Anti-TNF Medications

Here are three of the different anti-TNF medications that help make people

with RA better. Consider some of the similarities and differences.

* Etanercept (Enbrel)

- subcutaneous injection twice a week, stays in the body for four

days;

- no Medicare coverage.

- most health insurers will not cover etanercept until you have been

on full doses of methotrexate without adequate improvement.

- no Medicare coverage. The company that makes this, in some

situations, will give the drug free to patients who cannot afford it or

where the insurance company will not pay for it. Ask your doctor about this.

* Adalimumab (Humira)

- subcutaneous injection every other week, stays in the body for 14

days;

- no Medicare coverage; The company that makes this, in some

situations, will give the drug free to patients who cannot afford it or

where the insurance company will not pay for it. Ask your doctor about this.

- most health insurers will not cover adalimumab until you have been

on full doses of methotrexate without adequate improvement.

* Infliximab (Remicade)

- intravenous infusion (in doctor's office, clinic or hospital) every

8 weeks;

- stays in the body for 8 days;

- paid for by Medicare.

- needs to be taken along with weekly doses of methotrexate

Another new biologic agent

* Anakinra (Kineret), which blocks the action of another protein that

stimulates inflammation that causes inflammation called IL-1.

- subcutaneous injection daily

- stays in the body for only 6 hours

- not paid for my Medicare

A Final Note On Medication Decisions

Note the differences in how long these drugs stay in the body. The longer a

drug stays in the body, the longer you can wait between doses - which is

good. But the longer it stays in the body, the longer it stays around -

which can be a problem if you develop an infection.

All the new anti-TNF drugs cost about $13,000 a year, but most health

insurers cover them. However, two are not covered by Medicare. The one drug

that is covered by Medicare is given as an intravenous infusion; sometimes

allergic reactions occur, which require treatment with diphenhydramine

(Benadryl) or acetaminophen (Tylenol).

About 40% of our patients with RA develop the disease after 60 years of age.

Because of their age, they are more apt to have other medical problems that

predispose them to other medical problems. Thus, I might prefer to treat

them with a drug that stays around for a shorter period of time - but their

Medicare coverage relegates them to a drug that might not be my first

choice.

This example demonstrates that some medication decisions are personal

decisions, some are professional decisions, but some decisions are imposed

by health insurers. But nonetheless, these are extraordinary medications

that have made a profound improvement in people's lives.

http://www.hss.edu/Conditions/Rheumatoid-Arthritis/How-Decisions-Are-Made-In

-Ra-Treatment