Anti-Tumor Necrosis Factor Inhibitors - Multiple agents

TNF Blocker Patient Decision Aid

Should I take TNF blocker for my rheumatoid arthritis?


What is a                 Patient Decision Aid?

This decision aid gives you information about RA, the medications used to treat it, details about TNF blockers (TNF) and some questions to help you think through what is important to you.




You have 4 options to choose from

Your options

This decision aid should help you feel more confident about the reasons for your decision. When planning your treatment in the future, your doctor will find it useful to know these reasons too.

1. Continue

2. Start TNF

3. Discuss options other than TNF with your doctor

4. Defer your choice for now


Information about RA

Information About RA

RA is a disease where your body’s natural defense (immune) system is over active and can affect your whole body. It results in inflammation of the joint lining – particularly the hands, wrists and feet. This can affect you by causing general feelings of sickness like fatigue, fever, or loss of appetite in addition to swelling, pain and stiffness of the joints. Together these symptoms reduce your ability or interest to do important activities at home, work and leisure. It is usually a chronic disease which means that it typically cannot be cured but needs regular treatment over many years to control symptoms and minimize complications.

If no treatment is chosen the symptoms of RA will vary but continue for years. In addition, most people will have at least some damage to the joints. This can lead to disability and may even shorten your life. Recent research suggests people with RA, especially if poorly controlled, have a higher risk for heart attack and stroke.


Treatments for RA

Goals Of RA Treatment

The main goals of RA treatment are to suppress joint inflammation, reduce pain and swelling, and slow or prevent joint damage.

To reach these goals, there are three types of medication used: Non-steroidal anti-inflammatory drugs (NSAIDs), prednisone and disease modifying anti-rheumatic drugs (DMARD). Often all three types are prescribed together to control joint inflammation. DMARDs are usually started soon after the diagnosis of RA and continued for as long as the disease continues.

The table below shows these three types of medication and where TNF blockers fit.  There are now five TNF blockers approved for use in RA.  They are noted in the table below.

Information about TNF Blocking Therapy

Information about        TNF Blockers 

As you saw in the table, there are two types of DMARDs: synthetic drugs and biologic agents.  Synthetic drugs (like methotrexate, MTX) are chemicals that improve RA by directly ‘quieting’ the overactive inflammatory cells.  The second class of DMARDs is the biologic agents.  These are not chemicals, but proteins.  They also work to reduce inflammation, but do it differently than the synthetic drugs.  The proteins are targeted against the messengers that activate inflammatory cells.



To better understand this, imagine that your RA is like a football team.  If the referee removes the football in the middle of the game, players can’t pass the ball to one another and move down the field.  The game can’t advance.  In the same way, the RA process needs messengers (footballs) to move between different types of inflammatory cells.  One type of messenger is tumor necrosis factor (TNF).  The TNF ‘turns on’ the inflammatory cells in your body, allowing the RA process to advance.


TNF Blocker Options 


In this booklet, we’ll discuss the proteins used to remove the TNF messengers.  These proteins are called TNF alpha blockers.  There are many types of TNF blockers.  They each have different structures, but they all work like a sponge, soaking excess TNF from the blood and body tissues.  This prevents TNF from giving your inflammatory cells the message to turn on.

Because the way that TNF blockers are made, some have all human parts and others are part human and part mouse.  Although all of these are safe, the products made with both human and mouse parts have a little higher chance of causing side effects.

The table below shows the five currently available TNF blockers.  It compares how long they have been available on the market and how agents are taken.  Proteins cannot be taken orally because they would be broken down in your stomach before they could do their job.  Instead, they are given either as an injection in the skin (subcutaneous, or SC) or intravenously (drip into vein, or IV).  The table also lists how often the agent is taken and whether it is used with other DMARDs.  The dose, structure and each manufacturer’s web site are also included.

Understanding the Benefits

There are many benefits that come from taking biologic agents.  In terms of reducing and joint damage, biologic agents are the most powerful group of DMARDs.  while synthetic DMARDs work more slowly, you may feel benefits of biologics after just 2-6 weeks.  The full benefit will be felt after 3-6 months.  Another benefit is that proteins are not broken down by the liver.  Unlike other DMARDs, these don’t typically cause liver irritation.

One goal of taking a TNF blocker is to improve your RA symptoms.  If you improve you should expect less pain and stiffness.  Gripping, reaching and daily activities should also be easier.  You also may have more interest in taking on physical activity. 

It is common for doctors to prescribe TNF blockers in combination with another DMARD, like methotrexate (MTX).  For example, if you add a TNF blocker to your current MTX program, then you have about a 60% chance of your RA symptoms improving,  Another way to look at this is to see what happens if 100 patients add a TNF blocker to their MTX program.

The outcomes of 100 patients treated with TNF

Some patients improve more than others with a new treatment. After starting a TNF blocker and MTX about 35% of patients will have major improvement and about 15% will have their RA completely suppressed.

Improvements from LEF are usually sustained, which allows many patients to continue on it for 5 years or more.


How RA Joint Damage Progresses Without Treatment

How RA joint damage progresses without treatment 

The diagram below shows the course that RA may follow if no treatment is used. The top pictures show what the progression looks like on the outside, while the bottom pictures show what is happening to the joints under the skin.

One of the major problems of RA is that joint damage can begin in the first year of the disease and build up over time if the disease is not controlled. These pictures show how swelling of the joint lining can break down bone and cause “erosions” to form where the support ligaments attach. This weakens the joint and over time allows the joints to move out of line and deform.


How RA Joint Damage Is Slowed with TNF Treatment

One benefit of adding a TNF blocker to your treatment is its power to slow further joint damage.  Research has shown that the use of a TNF blocker along with MTX can notably reduce the rate of RA joint damage in most patients (compared to using MTX alone).

To better understand the idea that different DMARD programs can give different results, see the table and ‘Joint Damage Speedometer’ below.

Another way to look at this is to consider:

  • If you take no treatment you will have the expected amount of added joint damage (100%).
  • If you take MTX + TNF Blocker less damage will occur – about 5% or less of what would have been expected if no treatment was taken.

TNF Blockers                Slow Joint Damage 


Understanding Side Effects

Possible Side Effects

All drugs have the potential for benefit and harm. In the next few pages we have listed the most common, as well as some less common but serious, side effects. Part of being informed is having an idea of how often these events happen. This booklet is not meant to replace talking with your medical provider. Rather, its goal is to inform you and support your decision making.

Costs

The cost of  TNF blockers is not a side effect, but can be a burden and barrier to use.  Most TNF blockers cost about $1500/month or more.  Though this might seem like a staggering amount of money, it’s important to collect all of the facts about costs before making a decision.

For example, IV treatments may be covered more fully than SC injections by some insurance companies, including Medicare.  Also, there are private foundations and company co-pay cards that markedly reduce the cost.  You should talk with your medical team about payment options for these advanced treatments.  In most cases there are ways to make these types of treatments accessible to nearly all patients.

Conception

The safety of taking TNF blockers during pregnancy is not known.  Therefore, sexually active men and women using a TNF blocker must use a medically approved form of birth control.

Injection site reactions

For agents injected into the skin, injection site reactions can happen.  These are areas of slight redness, swelling and itching.  These reactions resolve within a day or two.  They are common in the first few months of taking the shot, but become less common and severe over time.

Infusion reactions

Agents given though the vein can cause infusion reactions.  Although there are different reasons for the reactions, the reaction caused by Remicade may be due to the body reacting to the mouse part of the agent.

Twenty percent of patients who receive an infusion develop a reaction.  These can be mild, with slight itching or a warm feeling.  More severe reactions can include headaches, low blood pressure, swelling or chest pains.  It is possible that an infusion reaction could be seere enough to cause death.  Because the reactions are varied, IV treatments are given at infusion centers or hospitals where doctors supervise the treatment.


Serious Infection

Types of Serious Infection 

Because TNF blockers reduce the activity of the hyperactive immune cells in RA, it can also reduce your ability to fight off infections.  There are three types of infections:  acute, chronic, and latent/ “sleeping”.

Acute infections

Acute Serious Infection

These are infections that begin rapidly.  They have a known cause and can be cured if given the proper treatment.  The most common types of acute infections people on TNF blockers might have are bronchitis or sinusitis.  These are not serious and can be easily treated.

TNF blockers also make it more likely that you will have serious acute infections like pneumonia, kidney infections, or skin infections.  When we refer to serious infections, we mean infections severe enough that you would need to be admitted to the hospital for one or more days to receive antibiotics through the vein and/or other care like IV fluids and oxygen.

If you are >65 years old, have another diseases such as diabetes or chronic lung disease, or take prednisone, your risk may be higher.  If you are young and healthy your risk may be lower.  TNF blockers should not be taken by persons with HIV (Human Immunodeficiency Virus).

If you choose to take a TNF blocker you have an added chance of about 5% each year of havinga serious infection.  Another way to look at this is to see what happens if 100 patients take a TNF blocker.

The outcomes of 100 patients treated with TNF blocker for 1 year


Chronic Infections

Chronic Infections

 TNF blockers can also lead to worsening of chronic infections.  Chronic infections are infections that begin slowly and can last for many years.  If a TNF blocker is used in a person with chronic infection, the body’s ability to control this infections can be reduced, resulting in the spread of the infection throughout the body.

Hepatitis B and C viruses are two examples of chronic infections.  These liver infections can occur for years, with very small amounts of virus present.  Although the safety of TNF blockers for people with hepatitis B or C is not fully known, most doctors feel that people with hepatitis B infections should not be treated with a TNF blocker.  If you have hepatitis C, you and your doctor should decide together whether or not you should use a TNF blocker.

Other chronic infections also make it unsafe to use a TNF blocker.  If you have  chronic skin ulcer, bone infections or another ongoing chronic infection, it is important that your doctor knows this.  These types of infections must be completely removed from your body before treatment with a TNF blocker is safe.

Latent Infections

Latent Infections

Latent infections are inactive (or sleeping) infections that can be awakened by RA therapy.  An example of this is a virus called varicella-zoster.  This virus causes both chicken pox (varicella) and shingles (herpes zoster).  Even after a child’s acute chicken pox infecion is over, the virus is never completely removed from the body.  Instead, the virus stays in your body and ‘sleeps’.  When the virus is asleep, you do not have any symptoms of the virus.  Later in life, it is possible for the skin infection called herpes zoster, or shingles.  It is possible that TNF blockers can wake up the sleeping virus.

TNF blockers can also awake two other types of infections: tuberculosis (TB) and fungal diseases.  Nine percent of Americans and 30% of people in the world carry TB in a latent state.  Latent TB sleeps in a person’s lungs.  SImilar to shingles, the TB virus can awake if someone is given treatments (like TNF blockers) that reduce the activity of the immune system.  If TB wakes up, it becomes active and spread to other parts of the body.  This can be a danger to you and others.  You could infect people around you- like your family and co workers- because TB is spread through the air.  The TNF blockers dosed less often (like Remicade) may have a higher risk of awaking TB than those given more often (Enbrel).

If you have a positive TB skin test and you take a TNF blockers and you do not take a preventative therapy, the chance of TB becoming active is 2-10 times greater.  If you do take a preventative therapy, the chance of TB becoming active is very small.

The two fungal infections, coccidioidomycosis (or Valley Fever) and histoplasma, also ‘sleep’ in your body and can be awoken if you take TNF blockers.  Histoplasma is a common infection in the Indiana/Ohio river valleys, but is can also occur in surrounding states, like parts of MIchigan.  Valley Fever is common in Arizona and southern California.  You can get these infections if you inhale dust from the soil of areas where these fungi live.  If you inhale the fungi, it enters your lungs.


Immune Reactions

Immune Reactions

Although TNF blockers can be used to treat diseases like RA, there are some immune diseases, like multiple sclerosis (MS), which can get worse if you take a TNF blocker.  Therefore, people who have MS should no use TNF blockers. Rarely, protein treatments- like TNF blockers- activate the body’s defense (immune) system.  A reaction like this can become a serious problem.  It may lead to nerve damage, lupus-like reactions, low blood counts, or other problems.  It is not known how often this occurs, but some experts estimate that 1 person our of 5,000 on a TNF blocker will have this kind of problem.  This is still being studied by doctors.  For more information about specific TNF blockers see the manufacturers’ medication guide.



Advice for Reducing Serious Side Effects

Suggestions for the safe monitoring of TNF blockers have been made by the College of Rheumatology.  While this will not prevent all problems, if you follow these guidelines you will likely detect problems earlier.  This should help your doctor to make adjustments and reduce serious side effects.


Sorting it Out

Sorting It Out

This is a good time to think back about what you know about your options and what is most important to you. While you might think the choice you face is simply whether or not to take TNF, there are at least 5 options available.


How do you make hard decisions?

How do you make hard decisions?

When making hard decisions it is sometimes helpful to see how others went about choosing what was best for them. 

Consider the people below. Do any of them approach decision making like you? When making hard decisions it is sometimes helpful to see how others went about choosing what was best for them. 


Weighing the Facts

Earlier we outlined possible benefits and side effects from taking LEF.

Possible Benefits

Possible Benefits

  •   Less pain, stiffness and fatigue
  •   Improve physical function
  •   Reduce progression of joint damage
  •   Prevent complications of active RA
  •   Use less prednisone (steroids)


Possible Side Effects

Possible Side Effects

  •   Infusion or injection site reactions
  •   TB reactivation
  •   Serious infection
  •   Immune reactions
  • Worsening MS or congestive heart failure if you already have either of them

Are any of these especially important to you?

What matters most to Me? 

What Matters Most to Me

Of the risks and benefits, are you clear what are most important to you?  While is it possible that you will not experience any of the side effects in this brochure, it is important to think about how you would feel if you did.

The table below lists some of the benefits and risks  of therapy.  In your mind rate how much each of these matter to you if they were to occur.


Moving Towards a Decision 

Moving Towards a Decision 

Now that you know more about TNF and have considered what is most important to you about the decision, are you leaning towards a particular choice? 

Some people find listing the pros and cons makes the decision clearer. Try creating a table like the one below and filling it out to sort out what matters most to you.

Conclusion

Conclusion

TNF blockers are powerful medicines that can help control RA, but there are risks in taking them.  Because RA is a chronic disease, you may need to take a TNF blocker for years.  This will mean that is you choose to take a TNF blocker you will have to be committed to taking the medicine and monitoring its safety.  Fortunately rheumatologists have of experience using TNF blockers in RA, and they can be used safely in most people.



Reflecting on your decision

Reflecting on your decision

As you work towards making a decision about TNF, decide whether these statements are true for you

  • I know the options
  • I am informed about the benefits and harms of treatment.
  • The doctor gave me a chance to be involved in the decision.
  • I feel an informed choice was made.
  • I will have the support I need to get, take and monitor the safety of the new medicine.

If most or all of these statements are true for you, you are on your way to a good decision. 

If not, you may want to talk further with your doctor, nurse, family or other important support persons.


Check what you know about TNF with these questions

Where can I get more information?


Facts and numbers behind this decision aid

Sources of data

  1. Donahue KE. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Annals Intern Med 2008;148:124-134.
  2. Bathon J. A comparison of etanercept and MTX in patients with early rheumatoid arthritis. N Engl J Med. 2000 Nov 30;343:1586-93. 
  3. Singh JA et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.  Arthritis Care Res (Hoboken). 2012 May;64(5):625-39.
  4. Package Insert: Remicade (infliximab) – Centocor, Inc. 2012
  5. Package Insert: Enbrel (etanercept) – Amgen & Wyeths. 2012.
  6. Package Insert: Humira (adalimumab) – Abbott Laboratories. 2012.
  7. Package Insert: Cimzia (certolizumab pegol) – UCB, Inc. 2012.
  8. Package Insert: Simponi (golimumab) – Centocor, Inc. 2012.
  9. Clinical experts such as rheumatology physicians and nurses when published sources were absent or conflicting. 

Reading level: SMOG: 9.9

Content Editor: Richard W. Martin, M.D., M.A. Professor of Medicine, Rheumatology. Michigan State University, College of Human Medicine. Author disclosure: No conflict to report.


Co-investigators: P Gallagher BS, A Head MD, A Eggebeen MD, J Birmingham MD.  

Technical and creative consultants:  R. Jelsema, Brennan Martin, Josh Quinn.

Acknowledgments:  The development of this patient decision was inspired by the work of a number influential basic and applied decision scientists.  We wish to acknowledge: Annette O’Connor PhD, John Wennberg, MD, Margaret Holmes-Rovner, PhD, Hillary Bekker, PhD, Gerd Giggerenzer, PhD, Timothy Wilson, PhD, Peter Ubel, MD, Adrian Edwards, MD and Glyn Elwyn, MD.


Funding:  This decision aid was developed, evaluated and published solely with private funds.  


Year of last update or review: 2013.


Copyright 2013 

West Michigan Rheumatology, PLLC 

1155 East Paris Ave. SE, Suite #100
Grand Rapids, MI 49546 

616-459-8088

www.mi-arthritis.com


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