Anti-B Cell Antibody Rituximab/Rituxan

Rituximab/Rituxan Patient Decision Aid

Should I take Rituximab/Rituxan 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 Rituxan 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 Rituxan (RTX)

3. Discuss options other than RTX 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 RTX fit.  

Information about Rituximab/Rituxan Therapy

Information About       RTX Therapy

The second class of DMARDs is the biologic agents. These are not chemicals, but are proteins. They also work to reduce inflammation, but do it differently than the synthetic drugs. RTX is made up of proteins targeted against one of the body’s overactive defense cells, called B-cells. 

B-cells have many functions in your body. One of their main tasks is to fight off infections by making antibodies against bacteria. Unfortunately, they also advance the RA process. One way they do this is by making the “rheumatoid factor”, a type of antibody. B-cells also make messengers that activate other inflammatory cells.


RTX helps reduce the progression of RA by depleting certain types of B-cells. Because RTX only targets certain B-cells, there are still enough B-cells available to make antibodies to fight off most bacteria. 

A unique difference between biologics is that some are made of 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 – like the B-cell blocker, RTX – have a little higher chance of causing some side effects. 

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 into the skin (subcutaneous, or SC) or intravenously (drip into the vein, or IV). RTX is given through an IV, which usually takes about 5 hours. 

RTX was first used in 1997 to treat non-Hodgkin’s lymphoma. In 2006, it was approved to be used to treat RA. It’s used in combination with methotrexate (MTX) and is typically prescribed if MTX and another treatment (i.e.TNF blocker like Enbrel) did not work. 

The RTX treatment is taken in two doses (2 weeks apart). These doses are given every 6 months. 

Take a minute to review the information just covered...

Understanding the Benefits

There are many benefits that come from taking biologic agents. In terms of reducing symptoms and joint damage, biologic agents are the most powerful group of DMARDs. While synthetic DMARDs work more slowly, you may feel some 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. So unlike other DMARDs, these don’t typically cause liver irritation. 

One goal of taking RTX 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 RTX in combination with another DMARD, like methotrexate (MTX). For example, if you add RTX to your current MTX program, then you have about a 52% chance of your RA symptoms improving. Another way to look at this is to see what happens if 100 patients add RTX to their MTX program.

The outcomes of 100 patients treated with RTX


Some patients improve more than others with a new treatment. After starting a RTX and MTX about 30% of patients will have major improvement and about 15% will have their RA completely suppressed.

Improvements from RTX 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 RTX Treatment

One benefit of adding a RTX to your treatment is its power to slow further joint damage.  Research has shown that the use of a RTX 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 + RTX less damage will occur – about 5% or less of what would have been expected if no treatment was taken.

RTX Slows Joint Damage


Understanding Side Effects

Understanding            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 RTX is not a side effect, but can be a burden and barrier to use. RTX costs about $9000 for a 6-month treatment. 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 other drugs by some insurance companies, including Medicare. Also, there are private foundations and company co-pay cards that markedly reduce 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 RTX during pregnancy is not known. Sexually active men and women using RTX must use a medically approved form of birth control. 


Low Blood Counts 

People with RA often have anemia (low levels of red blood cells). This can be caused by the disease, stomach ulcers or other effects from drugs. Sometimes RTX can reduce blood levels. This can cause fatigue, bleeding or increased risk of infection. 

To help prevent the side effects from low blood levels, you must take regular blood tests. For many people getting these blood tests is the most difficult part of taking RTX. The American College of Rheumatology recommends all persons taking RTX for RA have blood tests every 3 – 6 months as long as they continue on RTX. 


Infusion Reactions 

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

Thirty percent of patients who have a RTX 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 severe 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 RTX  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 Rituxan might have are bronchitis or sinusitis.   These are not serious and can be easily treated.

Rituxan also makes it more likely that you will have  serious acute infections like pneumonia, kidney, or skin infections.  When we refer to serious infections, we mean infections sever 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 other 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.  Rituxan should not be taken by persons with HIV (Human Immunodeficiency Virus).

If you choose to take Rituxan you have an added chance of about 2-3% each year of having a serious infections.  Another way to look at this is to see if 100 patients take Rituxan.

The outcomes of 100 patients treated with RTX for 1 year


Chronic Infections

Chronic Infections

RTX can also lead to worsening of chronic infections.  Chronic infections are infections that begin slowly and can last for many years.  If a RTX 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 RTX 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 RTX.  If you have hepatitis C, you and your doctor should decide together whether or not you should use a RTX.

Other chronic infections also make it unsafe to use a RTX.  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 RTX is safe.

Latent Infections

Latent Infection

Latent infections are inactive (or sleeping) infections that can be awakened by RA therapy.  A person with a latent infections probably does not have any symptoms of infections.  An example of a latent infection is tuberculosis, or TB.  Latent TB “sleeps” in a person;e lungs, walled off by your body’s immune system.  The TB bacteria 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 can 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 or co-workers- because TB is spread through the air.

RTX has not been known to awaken latent/sleeping TB.  But because other biologics (TNF blockers) have been reported to awaken TB, the American College of Rheumatology suggests all people who take Rituxan get screened for TB before starting a while taking RTX.

If you have a positive TB skin test and you choose to take Rituxan and you do not take a preventative therapy, it is possible the chance of TB becoming active is increased.  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 biologics like RTX.  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

Although biologics like RTX can be used to treat diseases like RA, there are some immune diseases, like multiple sclerosis (MS), which can get worse if you take another type of biologic called TNF blockers.    Therefore, people who have MS should no use TNF blockers. This does not appear to be a problem with RTX, however rarely, protein treatments, like Rituxan, can 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.  This is still being studied by doctors.  For more information about RTX see the manufacturers’ medication guide.


Other Side Effects

People with RA have an increased risk of developing lymphoma. It is not known what effect RTX has on this risk. Research is being done to help understand the relationship between RTX and cancers. RTX remains a major treatment for lymphoma. 


Advice for Reducing Serious Side Effects

Suggestions for the safe monitoring of RTX 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?

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. 

How do you make        hard decisions?


Weighing the Facts

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

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 reaction
  •   Serious infection 
  •   Infusion reaction
  •   Immune reactions
  •   Rare infection like PML

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 RTX 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

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



Reflecting on your decision

Reflecting on your decision

As you work towards making a decision about RTX, 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 RTX 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.   Package Insert: Rituxan (rituximab) – Genentech, Inc. 2010.

3. 1.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.  Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane reviews. 2010. DOI: 10.1002/14651858.CD007848.pub2

5. 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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