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Guide to living with rheumatoid arthritis: Part 1

July 5, 2017
Have you recently been diagnosed with rheumatoid arthritis? RheumDoctor presents a guide to living with rheumatoid arthritis

Rheumatoid arthritis…  Your rheumatologist diagnosed you with rheumatoid arthritis and you have a lot questions.  What’s rheumatoid arthritis?  Can I get rid of it or will I live with this disease for the rest of my life?  What should I expect?  How do I fight it?  This week I’ll present to you Part 1 of a Guide to living with rheumatoid arthritis.  I’m going to present this as a three-part series.  Part 1 will cover the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, treatment, etc.  In Part 2 I’ll cover prognosis, what to expect, diet and exercise.  In Part 3, I’ll be covering the financial side of rheumatoid arthritis: How to get access to medications and how to deal with insurance companies.

I hope you find this information useful.  Be strong, be brave, and know that you’re not alone.

What is rheumatoid arthritis?

Rheumatoid arthritis is an autoimmune disease that causes inflammation throughout the body but mainly affect joints. Without treatment, rheumatoid arthritis can eventually lead to permanent joint destruction.  Autoimmune diseases occur when the immune system loses “tolerance to self”.  What this means is that the immune system can no longer distinguish between healthy cells and cells that don’t belong like bacteria or cancerous cells.

According to the CDC, about 1% of people living in the US suffer from rheumatoid arthritis.  It tends to occur 2-3 times more often in women and tends to start in your sixties but it can start at any age.  [1]

Some common signs and symptoms include:

  • Pain and swelling in the joints. Particularly small joints like the knuckles, wrists, and toes.
  • Morning stiffness that lasts more than one hours
  • Having difficulty opening jars. Weakness in the hands.
  • Fatigue, fevers, unintentional weight loss.

What causes rheumatoid arthritis?

We’re actually unsure.  We do know that in certain cases there is a genetic link. People that have a certain HLA class II genotype (shared epitope) tend to get rheumatoid arthritis more often.  Especially, if they smoke cigarettes.  Moreover, we know that rheumatoid arthritis tends to run in families.  However, most cases of RA happen spontaneously and not everyone who has a genetic risk factor develops RA.

There’s still a lot of work that needs to be done to fully understand what causes rheumatoid arthritis.  Like most autoimmune diseases, our best guess is that people who have RA probably were born with some sort of genetic predisposition for the disease.  Then they get exposed to something in the environment like a virus, trauma, stress, hormonal change, which then triggers the disease to come online.

What are the symptoms of rheumatoid arthritis?

Usually rheumatoid arthritis presents with pain, swelling, and prolonged stiffness involving small joints, like the ones in your hands or feet.  When I mean prolonged, I mean more than one hour.  But RA can present in many ways. These can be divided into typical (90% of cases) and atypical presentations (10% of cases).

Typical

Insidious (55% – 65%): People develop pain, swelling, and prolonged stiffness mainly involving small joints like the toes and knuckles. This progressively worsens over months.

Subacute (15% – 20%): Again small joints are painful, swollen, and stiff but the this develops over weeks. Usually people experience some fatigue.

Acute (10%): Joints suddenly become swollen and tender over days. Some people have a fever, drenching night sweats, and sometimes can lose weight without trying.

Atypical (10% of cases)

Palindromic pattern: This type of presentation isn’t technically considered rheumatoid arthritis. It’s just that 33% to 50% of people with this type of presentation progress to full-blown rheumatoid arthritis. Typically, one joint is involved. It becomes tender and swollen for a few days then gets better on its own. Then a few weeks to a few months later it happens again. The flare can happen in the same joint but not necessarily. Treatment with hydroxychloroquine can decrease the risk of developing full-blown rheumatoid arthritis, so it’s important to start treatment as this stage.

Insidious onset of the elderly: As the name suggests this type of presentation occurs in the elderly, so people aged greater than 65 years. People experience extreme pain and stiffness shoulders and the hips. Sometimes you can see whole hand or foot swelling. Sometimes it’s very difficult to differentiate from polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema (RS3PE).  People with polymyalgia rheumatica and RS3PE typically do NOT have any positive antibodies.

Rheumatoid nodulosis: Rheumatoid arthritis can cause nodules and bone cysts on radiographs. Usually people also have joint pain and swelling but sometimes all they have are nodules.

Arthritis robustus: This is rather rare. I’ve only seen it once. It typically occurs in men. Essentially the person develops horrible rheumatoid arthritis hand deformities but experiences little or no pain.  I know it’s hard to believe, but it’s possible!

Untreated rheumatoid arthritis

By James Heilman, MD (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

How is rheumatoid arthritis diagnosed?

The diagnosis of rheumatoid arthritis, contrary to popular belief, is primarily a clinical diagnosis. Having a positive antibodies like a rheumatoid factor (RF) does not necessarily mean that you have rheumatoid arthritis because MANY conditions can have a positive rheumatoid factor. Some of these include:

Rheumatoid arthritis, mixed cryoglobulinemia types II and III, sarcoidosis, and other autoimmune diseases like Sjogren’s syndrome. Other non-rheumatology diseases that can cause someone to have a positive rheumatoid factor include infections most notably hepatitis C, tuberculosis, syphilis, HIV, and endocarditis. People suffering from cancer and people with chronic pulmonary and liver diseases, can also have a positive rheumatoid factor.

It’s also important to mention that about 5 – 25% of people aged 60 years and older have a positive rheumatoid factor without any underlying causative disease.

This is why my job as a rheumatologist is so interesting 🙂

The American College of Rheumatology classification criteria for rheumatoid arthritis is as follows:

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis[2]

Who to test?

  • People that have at least 1 joint with definite swelling.
  • And the swelling cannot be better explained by another disease.

Classification criteria for RA (a score of ≥ 6/10 is needed for someone to have definite RA)

Category   Score
A Joint involvement

1 large joint

2 – 10 large joints

1 – 3 small joints

4 – 10 small joints

> 10 joints (at least one small joint)

 

0

1

2

3

5

B Antibodies

Negative RF and negative CCP antibodies

Low positive RF or low positive CCP antibodies *

High-positive RF or high positive CCP antibodies #

 

0

2

3

C Inflammation markers

Normal CRP and normal ESR

Abnormal CRP or abnormal ESR

 

0

1

D Duration of symptoms

< 6 weeks

≥ 6 weeks

 

0

1

* Low positive antibodies means any value that is above normal but less than 3 standard deviations above the upper limit of normal.

# High positive antibodies means any value that is 3 standard deviations above the upper limit of normal.

It’s important to note that these criteria were NOT meant for clinical practice but rather, were really meant for research trials. Sometimes, rheumatologists do deviate. Other conditions should be ruled out and let’s face it, not everyone fits perfectly into the mold. The criteria also does not account for musculoskeletal ultrasound testing. This imaging test can detect very subtle inflammation of a joint.[3]

Positive antibodies without RA

Now sometimes the workup is completely negative including x-rays. This is not uncommon. It can mean many things. It could mean that the rheumatoid factor is not clinically significant. 5–25% of the population can have a positive rheumatoid factor without any underlying condition or any symptoms. Typically the rheumatoid factor levels are low. It could also mean that you will develop rheumatoid arthritis in the future. Studies have shown that antibodies associated with rheumatoid arthritis can be present over a decade before onset of clinical disease. [4]Unfortunately, we don’t have the tools to precisely determine who will convert and who will not. In this situation, your rheumatologist can help you watch for any change in your condition.

How is rheumatoid arthritis treated?

We treat rheumatoid arthritis with medications called disease modifying anti-rheumatic drugs (DMARDs).  These medications slow down or stop the natural progression of rheumatoid arthritis.

Except for a few special situations, EVERYONE should with rheumatoid arthritis should be treated with a DMARD as soon as possible because permanent joint damage can happen in as little as 3 months after symptoms start.[5]

The following are the medications used to treat rheumatoid arthritis in the United States.  It’s important to work closely with your rheumatologist because they all have possible risks and what may be good for your neighbor may not be safe for you.

I’ve broken them down into conventional DMARDs, biologic DMARDs, and pipeline medications that have not been approved as of yet.

Conventional

  • Methotrexate
  • Leflunomide
  • Sulfasalazine
  • Hydroyxchloroquine

Biologics

  • Etanercept, TNF inhibitor
  • Adalimumab, TNF inhibitor
  • Golimumab, TNF inhibitor
  • Certolizumab pegol, TNF inhibitor
  • Infliximab, TNF inhibitor
  • Abatacept, Co-stimulation inhibitor
  • Tocilizumab, IL-6 inhibitor
  • Sarilumab, IL-6 inhibitor
  • Tofacitinib – JAK inhibitor
  • Rituximab – B cell depletion

Pipeline

  • ABT 494, a new JAK inhibitor
  • Baricitinib, another JAK inhibitor
  • Sirukumab, another IL-6 inhibitor

Biosimilars

It’s also important to note that we are starting to see biosimilar medications in the States. These are medications that are sort of copied from existing biologic medications.  They are NOT generic medications. The problem with biosimilars is that because of their complexity, it literally is impossible to exactly copy a biologic medication. If you want to learn more about biosimilar medications, please check this article.

Supplements

If you’re interested in supplementing, there is some research that suggests high dose turmeric/curcuma and high dose fish oil/omega-3 fatty acids may also be helpful.[6][7] However, supplementation should be used in combination with FDA approved medications that I listed above.

Is there a cure for rheumatoid arthritis?

I honestly wish I had better news for you. Unfortunately there is no cure for rheumatoid arthritis. Treatment primarily focuses on arresting the natural progression of the disease with the use of disease modifying anti-rheumatic agents (DMARDs). Conventional DMARDs such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, modulate the immune system to decrease rheumatoid arthritis activity.  Biologic medications like etanercept use a targeted approach, i.e., suppress a specific cytokine.

The goal of treatment is to put rheumatoid arthritis into remission and decrease the frequency of flares.

This may seem very pessimistic, but recent advances have really improved the prognosis of people living with rheumatoid arthritis.

Nevertheless, DMARDs do not cure rheumatoid arthritis.

How do we win the war against rheumatoid arthritis? Before we can win the war and find a cure, we need to know exactly what causes rheumatoid arthritis in the first place and we need to understand its exact pathophysiology. Believe it or not, despite all our advances, we still cannot answer these two questions. Don’t despair, researchers are actively trying to answer these questions.

Can rheumatoid arthritis become fatal?

Rheumatoid arthritis is a systemic autoimmune mediated disease that primarily affect the joints. Note the primarily bit. It can affect a host of different organs including the eyes, lungs, heart, skin, and bone marrow to name a few.

Untreated or poorly controlled rheumatoid arthritis can cause serious conditions such as interstitial lung disease (i.e., inflammation of the lungs), pericarditis (i.e., inflammation of the “sac” surrounding the heart), as well as something called Felty’s syndrome (i.e., a hematologic condition that can cause white cells to dramatically decrease and causes the spleen to enlarge). These severe manifestations of rheumatoid arthritis that can lead to death are hardly ever seen anymore mainly because we have many highly effective medications called disease modifying anti-rheumatic medications (DMARDs). These medications have completely changed people’s prognosis.

Cardiovascular disease and infection

The most common cause of death in people with rheumatoid arthritis these days includes cardiovascular disease and infection – primarily from medications.[8]

Rheumatoid arthritis increases cardiovascular risk via the interplay of inflammation and lipid metabolism. Studies have shown that people who receive treatment with methotrexate and or tumor necrosis factor inhibitors reduce their cardiovascular risk.[9] A British study also demonstrated that cardiovascular was not increased regardless of the choice of DMARD provided that rheumatoid arthritis was well controlled.[10]

Infection remains an ever-present problem in the world of rheumatology. To treat autoimmunity you need to suppress the immune system. Not too much, not too little, but just right. In some cases this has the unfortunate result in causing serious infections that can lead to death in extreme cases.

Rheumatoid arthritis can become fatal in many other ways, however, for the most part it is medication induced – although the pharmaceutical companies don’t really want you to know that. Just read a package insert. They’re terrifying.

However, I’ve been talking about rheumatoid arthritis fatalities. Untreated or undertreated rheumatoid arthritis is HIGHLY debilitating leading to a significant drop in your quality of life. Early treatment with a DMARD is the best way to improve your odds. You have to fight fire with fire!

Can I stop my medications if I’m feeling better?

No. Rheumatoid arthritis is a life-long disease.  If you’re feeling better, great!  However, it’s probably your medications that are keeping you that way.  If you stop your medications the rheumatoid arthritis will come back.  Maybe not now but soon.  Rheumatoid arthritis subsides spontaneously in a VERY small subset of people.

If your medication is making you feel sick, talk to your rheumatologist.  They’re there to make you feel better and they want to find the perfect treatment plan tailored for you.

Do not stop your medications without consulting your rheumatologist.

Next steps

We’ve covered a lot of material today and there’s a lot more coming your way!  Stay tuned for Part 2.  I’ll be covering topics such as what to expect, what to eat, how to exercise, and strategies on how to reduce stress.  Please leave your comments below.

References

[1] https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html

[2] https://www.rheumatology.org/Portals/0/Files/2010_revised_criteria_classification_ra.pdf

[3] Horton SC, et al. Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis. RMD Open. 2017 Mar 30;3(1):e000394. doi: 10.1136/rmdopen-2016-000394. eCollection 2017.

[4] Brink M, et al. Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis. Arthritis Res Ther. 2016 Feb 9;18:43. doi: 10.1186/s13075-016-0940-2.

[5] Raza K, et al. Treating very early rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2006 Oct;20(5):849-63.

[6] van der Tempel H, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis. 1990 Feb; 49(2): 76–80.

[7] Ramadan G Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officiale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. 2011 Aug;34(4):291-301. doi: 10.1007/s10753-010-9278-0.

[8] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/26472415

[9] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28455580

[10] https://www-ncbi-nlm-nih-gov.elibrary.amc.edu/pubmed/28160488

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Featured Overcoming Inflammation

What is the best diet for autoimmune diseases

June 21, 2017
What are some foods have anti-inflammatory properties?

In recent years there’s been a lot of talk about the autoimmune diet. But what exactly is an autoimmune diet and which foods have anti-inflammatory properties?  These are some of the most common questions my patients ask me in clinic.  Essentially, what foods help autoimmune diseases?  In certain cases, it’s pretty cut and dry.  If you have celiac disease, avoid gluten.  If you have ankylosing spondylitis, Crohn’s disease, or ulcerative colitis, try to follow the FODMAP diet.  There already exists evidence-based research that supports these interventions.

But what about other autoimmune diseases like rheumatoid arthritis, lupus, Sjogren’s syndrome?  What should you be eating if you have any of these?  Do they have their own autoimmune diet?  Should you avoid nightshades, dairy, gluten, eggs, etc.  In recent rears a myriad of “anti-inflammatory diets” have surfaced on the web.  For the most part, they are supported by little if any evidence-based research.  This is unsurprising.  Good quality research requires money.  Lot’s of money… pharma money.  It simply does not make any business sense for these companies to fund large and expensive studies that have no commercial potential.  Believe me, I am not defending big pharma, I’m simply stating reality.

What is epigenetics?

Even though we do not have great scientific evidence supporting a particular autoimmune diet or foods to prevent, cure, or lessen autoimmune diseases, it’s kind of obvious that some lifestyle practices lead to better health outcomes.  Take smoking.  People that smoke tend to get lung cancer and develop heart disease compared to those that don’t smoke.  But how does that work exactly?

Everyone is born with genes.  Some of these genes are active and some remain dormant.  Your genotype is the entire makeup of your genes.  Your phenotype is the result of how your genetic material is expressed.  For example, you may have the genes for blue eyes and brown eyes.  If the genetic material for brown eyes is dominant, you’ll have brown eyes.

This is where it gets really interesting.  Over the course of your lifetime, some of your genes are turned on and off.  This is influenced by factors like aging, the environment, and lifestyle.  Epigenetics is the study of how genes are turned on and off based on external influences.

Epigenetic changes can be good but can also cause harm.  We think that some of these changes can result in autoimmune diseases.  It’s important to remember that epigenetics is in its infancy.  Researchers still are not 100% sure how this happens, let alone, how to specifically manipulate the environment to cause favorable epigenetic change.

Autoimmune diet: what foods should I eat?

This simple answer to this question is, “I don’t know”.  One day, when researchers crack the epigenetic code, I may be able to answer this questions more accurately.  I may be able to tell you, if you follow the rheumatoid arthritis autoimmune diet, this should help control your inflammation.  Unfortunately, I am unable to say that yet.

But like I was saying at the beginning of this post, some people who adhere to certain lifestyle practices tend to be healthier.  Given we don’t really have actionable epigenetic data to guide lifestyle choices, the goal when it comes to nutrition and lifestyle is to adopt habits that have a tendency to result in overall general health to live happier, healthier, and longer.

The Blue Zones®

The Blue Zones® are 5 regions in the world where people statistically people tend to live to 100 years AND who tend to reach this age in health.  The project spawned from the National Geographic Society.  The goal was to find “hot spots of longevity” around the world.  The researchers identified 5 zones and circled them in blue ink.  These regions are as follows:

  • Ikaria, Greece
  • Okinawa, Japan
  • Ogliastra region, Sardinia
  • Loma Linda, California
  • Nicoya Peninsula, Costa Rica

One would think that there are no similarities between people living in Japan versus people in Greece.  What the researchers identified was a core list of lifestyle practices and environmental factors that shared between all the different regions.

The Power 9®

Move Naturally

People that live to 100 years don’t necessarily run marathons or go the gym.  They are always on the go and they move naturally.  For example, they tend a garden, they walk to the market, they use stairs instead of the elevator.

Purpose

People that live in the Blue Zones live with purpose.  They wake up every morning, and they know “why I wake up in the morning”.  Having a clear purpose in life can add an extra 7 years of life expectancy.

Down Shift

We all know that stress can cause inflammation.  I often see people in my clinic who’s rheumatoid arthritis was in perfect control until something really bad happened, like a divorce, job loss, or a death in the family.  Chronic stress leads to chronic inflammation.  People in the Blue Zones develop daily habits to help reduce stress.

80% Rule

The Japanese have a saying “Hara hachi bu”.  This is a mantra that Okinawans say before every meal, reminding them to stop eating when they feel about 80% full.  There is a delay between feeling full and actually being full.  When you feel 80% full, you are actually full.  So if you stop eating when you feel full, you are overeating.  People living in the Blue Zones tend to eat their largest meal at breakfast and their smallest meal at dinner.

Plant Slant

Although not all regions of the Blue Zones eat meat, their diets all mainly consists of fresh veg and beans.  Lot’s of beans: fava, soy, lentils, etc.  They eat meat very sparingly and servings are small, “about the size of a deck of cards”.

Wine @ 5

Thank goodness for this one!  People in the Blue Zones, expect for Adventists, drink alcohol moderately and regularly.  Typically, they drink 1-2 glasses of wine per day with friends and family at the end of the work day.  They found that people who drink regularly and moderately tend to live longer than those who don’t.

Belong

Almost all people who live until 100 tend to belong to some sort of faith-based community.  They found that attending a service 4 times a month can add up to 4 – 14 years of life expectancy.

Loved Ones First

People living in Blue Zones tend to live close to their families.  It’s common to have children, parents, and grandparents living under the same roof.  They also tend to commit to a life partner.

Right Tribe

People in the Blue Zones keep strong social networks.  Not only are these social strong, but they also foster healthy behaviors.  Women in Okinawa create “moais” early on in life.  These are groups of 5 friends that are completely committed to each other for life.


The true beauty in the Blue Zones Project® is that you don’t need to live in a Blue Zone to reap the benefits.  By living the Power 9® you can set yourself up to live with vitality to a ripe old age.

Conclusion

Medications certainly have made a huge difference in the prognosis of many autoimmune diseases like rheumatoid arthritis and lupus but it’s not enough.  By integrating healthy habits we can potentially turn on an and off genes that contribute to ongoing autoimmunity and inflammation.  Although we still don’t know exactly what the perfect autoimmune diet is, by adopting healthy habits set forth by the Power 9®, you can increase your odds to live a long, happy and healthy life.

Diseases and Conditions Featured

Biosimilars: How they may affect your autoimmune disease?

May 10, 2017
Biosimilars: How they may affect your autoimmune disease?

You may have recently heard about biosimilars for many autoimmune diseases like rheumatoid arthritis, psoriatic arthritis, and Crohn disease or maybe you haven’t even hear about biosimilars at all! A biosimilar is a medication that is a “copycat” version of a biologic but may have some small differences. The patent, which prevents other companies from making a product, on many biologics will expire soon opening a new opportunity for the development of biosimilars. While these medications are just beginning to come into the US market they you can already find them in Europe.

What are biosimilars and what can I expect when I use them? Are they better than the real medication, what is the cost? Read on to get the answer to all these questions and more!

What is a Biosimilar?

First of all, to understand biosimilars you must first understand what biologics are. Biologics are a class of medication used to treat many different autoimmune diseases.  Scientist make biologics with living cells or tissues inside a yeast or bacteria.  They are very complex molecules. Conventional medications, like methotrexate and hydroxychloroquine, are produced through specific reactions which produces a very precise molecule with a distinct structure. These medications are the same every time, the same materials, used in the same way produce the same drug.  These molecules are NOT complex. Biologics don’t always make an exact replica as living cells make them.  These are sensitive to the environment including light, temperature and nutrients.

Now add in the addition of a biosimilar. A biosimilar is a biologic that if it can show that it is “highly similar” to another, already approved biologic.  The original biologic is the “reference product”. The FDA requires these products to meet strict safety and efficacy standards just like biologics. The company then needs to prove that their biosimilar is a match for the already approved product for a particular disease.  After this happens, the biosimilar automatically gets approval to treat other diseases the reference product already has approval for.  For example, a biosimilar that has approval for rheumatoid arthritis would then automatically get approval for psoriatic arthritis if the reference product has approval for both.

Isn’t this the same as a generic?

The reality is that it’s a little bit more complicated than that. Think of a brand and generic medication as the recipe for a hamburger at a fast food chain. If you follow the same recipe you get the same hamburger every time, a hamburger in China tastes the same as one made in Albany, NY. Biologics and biosimilars are more like the recipe for sourdough bread. You can follow the same recipe every time but if the weather is different the bread may turn out different. The bread may have a slightly different texture but it will still fulfill its purpose. So biosimilars are not generics because they are NOT exactly the same as their reference medication.  It’s just that the difference is so small that it really should work about the same.

Cost savings?

Treatment with biologics is expensive. But the benefits, like an increase in quality of life, far outweighs the cost. What if you could get similar effects at a decreased cost? That is where biosimilars come into the picture. After the patent on a biologic has expired other companies are able to create drugs using the same process to get a biosimilar medication. Multiple companies producing the same product forces competition and a decrease in price.  This is what theoretically should happen.  In reality, we actually don’t anticipate a significant decrease in cost partly due to the complex process to produce the product.

How will I know what the medication is?

Biosimilars will have the same base name as the biologic they replicate. They will have an extra suffix after the name to differentiate them from the replicated drug. Naming the products in this way ensures you know what drug it replicated (through the base name) and that it is not the “real thing”, but in fact a biosimilar (through the suffix). For example, infliximab is the generic name for Remicade- the branded version. The biosimilar produced by Janssen Biotech is infliximab-dyyb. The addition of the “dyyb” shows that it is a biosimilar to infliximab.

If I have an allergy to the reference medication, am I allergic the biosimilar medication?

Just because you are allergic to the reference medication does not mean you will be allergic to the biosimilar, but it also does not mean you won’t be. True antibody derived allergic reactions are uncommon. Injection site reactions are much more common. There are many factors that can affect if you will have a reaction and what type of reaction it will be.

Some of these factors include:

  • Source of the protein used to make the biosimilar
  • What type of cell the protein was made in
  • Alteration in the protein structure. This can occur from something as simple as a change in storage temperate to changes in the manufacturing process.

As always, if you experience any type of reaction, call your doctor or get to an emergency center right away.

What biosimilars are approved in the U.S.?

At the time of this post there 4 products which have FDA approved biosimilars. This includes

  • adalimumab-atto, biosimilar to Humira (adalimumab)
  • etanercept-szzs, biosimilar to Enbrel (etanercept)
  • infliximab-abda and infliximab-dyyb, biosimilar to Remicade (infliximab)
  • filgrastim-sndz, biosimilar to Neupogen (filgrastim)

There are many other products currently being studied and this list will soon grow larger.

Is it as good as the real thing? What should I expect?

This is probably your biggest concern with using a biosimilar. When you find a treatment that works, you don’t want to jeopardize your health by changing your medications. Believe me, neither does your doctor. Maybe you are wondering if a biosimilar will do the same and possibly save you money? The FDA approval process ensures that biosimilars are just as effective (AND SAFE) as the biologic being replicated. Researchers need to prove that their product has the same clinical effect as the reference product. In the U.S., the FDA require strict safety and efficacy studies prior to approval and post-marketing studies.  These efforts help clinicians keep track of real-world experience with newly approved medications. Over the next few years it will be important for both patients and providers to stay up-to-date with post-marketing information related to the use and experience with biosimilars.

Do you have any experiences using biosimilars? Share them below!

 

Author: Alexis Bruno, Doctor of Pharmacy Candidate graduating May 2017 from Albany College of Pharmacy and Health Sciences.

Reviewed and approved by:  Jessica Farrell, PharmD.  Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

 

References

  1. Center for Biologics Evaluation and Research. What Are “Biologics” Questions and Answers [Internet]. U S Food and Drug Administration. Center for Drug Evaluation and Research; 2015 [cited 2017Mar26]. Available from: https://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cber/ucm133077.htm
  2. Center for Drug Evaluation and Research. Information on Biosimilars [Internet]. U S Food and Drug Administration. Center for Drug Evaluation and Research; 2016 [cited 2017Mar26]. Available from: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/
  3. Biosimilars: More Treatment Options Are on the Way [Internet]. U S Food and Drug Administration. Office of the Commissioner; 2016 [cited 2017Mar27]. Available from: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm436399.htm
  4. What is a biosimilar medicine? Supplemental Guide. NHS England. 2015 September 24.
  5. How biosimilars are approved [Internet]. 2017 [cited 2017 May 1]. Available from: http://www.amgenbiosimilars.com/the-basics/how-biosimilars-are-approved/
  6. Christl L. Biosimilar product labeling [Internet]. U S Food and Drug Administration. Center for Drug Evaluation and Research; 2016 [cited 2017Mar27]. Available from: https://www.fda.gov/Drugs/NewsEvents/ucm493240.htm
  7. Center for Drug Evaluation and Research. List Of Licensed Biological Products With (1) Reference Product Exclusivity And (2) Biosimilarity Or Interchangeability Evaluations To Date. US Food and Drug Administration, 2017. [cited 2017 May 1] Available from : https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM549201.pdf
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10 powerful life lessons to help overcome adversity

January 2, 2017

2017 is upon us and is gearing to be very interesting.  It’s going to be a year of change.  Lots of changes.  Whether for the better or for the worse remains to be determined… but I’m NOT going into any politics.  Lol!

We can’t deny that 2016 is over and it’s been a whirlwind both in the world of foreign and domestic affairs.  These events may even have affected your life in some way or another: ridiculous increase in your insurance premiums?  Your insurance company decided to not cover your medications anymore without any real justification? Maybe your health took a turn for the worse?  While we can’t control everything that happens around us, we certainly can look inwards and develop strategies to not only cope with adversity, but overcome and thrive.  Why be a victim when you could be a conqueror?

So far, I’ve been blessed with perfect health.  Living with with a chronic illness is tough.  It can devour you and unfortunately, sometimes it comes to define you.  But it doesn’t need to be that way.

I’d like to share with you a very personal story about the bravest, noblest, most compassionate, and selfless person I have ever met: Paul Feeney.  Maybe you may find some positive inspiration learning from his struggles but I secretly hope you learn most from his struggle.

Back in 2013, after fighting esophageal cancer for just shy of 2 years, my husband Paul passed away.  His passing is not the point of this post, but rather what he has to teach each one of us about adversity, courage, dignity, and the genuine love of life.

Here’s a picture of Paul doing dips at the gym.  Sorry for the poor graphics.  My phone was kind of basic and not that great back then.  But I digress.  That little pack he has around his waist, that’s chemo. More precisely fluorouracil (5-FU), and it’s pumping directly into his veins.  I believe I took this picture during his second or third month of chemotherapy with cisplatin and 5-FU.  This regimen is downright nasty.  He probably felt like shit, pardon my French, but you would never know because he would never let you know.  Some of you may know someone like this.  The eternal stoic.

After he passed away, I had to clean out his office.  In the process, I found treasure.  He never kept a diary, just thousands of random pieces of paper with incredibly insightful messages, intermixed with tax receipts, and to-do lists.  Here is a list of his 10 powerful life lessons.

 

 

Like most people’s fight with cancer, Paul’s was both brutal and bloody for his mind, body, and soul.  Despite all odds, throughout his illness he successfully continued running a business, he continued his Marine Corps exercise regimen x5 days a week, maintained an active social life, and continued being a doting son and husband.  During his struggle, he never let the disease define him.  It was something that he needed to overcome:

I have plans!

But sometimes, no matter how positive you are, no matter how proactive you are, and no matter how much you try, you simply can’t win them all.

The day before he passed, when there really was no hope, his physician walked into his room and told him there was nothing more he could do.  We had exhausted all avenues.  He had maybe two more weeks to live.  Paul calmly stood up, shook his doctor’s hand like a true gentleman and thanked him for everything he had done.

We may not choose to suffer, but we can choose how to face suffering.  Be kind, hold yourself to a higher standard, choose to be happy.  How will you face your Goliath?

Capt. Paul W. Feeney (July 23, 1963 – May 4, 2013)

Diseases and Conditions Featured

What is an ANA and what does it mean?

December 12, 2016

The antinuclear antibody is one of the worst tests in the history of all humanity.  It is my constant companion.  Why… I’ll get to that.

First, a little background.  What exactly is an antinuclear antibody, also known as an ANA?  In simple terms, an ANA is an antibody that is directed towards or attacks the nucleus of a cell.

How is an ANA measured?

The ANA is calculated by taking a standardized cell from the lab and mixing it with a person’s blood.  If a person has antinuclear antibodies, these will stick to the standardized cells’ nuclei.  At this point, there’s no way for us to know whether this has happened, so the lab tech adds fluoresceinated antibodies to the mix.  These antibodies bind to ANAs that stuck to a nucleus.  With the help of a specialized microscope, the lab tech can now visualize the ANA because the fluoresceinated antibodies make them light up like a Christmas tree.

My doctor told me my ANA was high.  What does that mean?

Unfortunately, the tech cannot count how many ANAs they see.  Instead, they see how much they can dilute the person’s blood and still see the fluoresceinated antibodies.  So when you see and ANA of 1:80, that means the tech really wasn’t able to dilute very much.  This is a low level.  If you see a value of 1:640, that means they were able to dilute way more.  This is a higher level.

What is considered a positive ANA?  That answer really depends on the lab.  Every lab has different cut off values, but in general, an ANA of 1:80 is typically considered positive.  Whether it is clinically significant, is a whole different question.  This is where the art of medicine comes into play.  But before that, let’s talk about patterns because those are important too.

So let’s take an example.  Your doctor runs an ANA and it comes back as 1:320 speckled pattern.  So what does that mean?  When the lab tech was looking at the fluoresceinated antibodies, it basically literally looked speckled.  There are many other kinds of patterns: homogenous, centromere, nucleolar, speckled, rim etc.  Each of these patterns are associated with a set of specific nuclear antibodies.  For example, the speckled pattern is associated with SSA, SSB, RNP, Smith, and Ku antibodies.  These specific nuclear antibodies are themselves associated with specific autoimmune diseases.  It’s important to take ANA patterns with a grain of salt because interpretation highly depends on the experience of the lab tech.

I’m not going to go more into details regarding specific nuclear antibodies because first, there’s about 150 of them and second, they’re all associated with different diseases lupus being one of them.  That’s a lot of material to cover in one article.

When is an ANA clinically significant?

Now that we understand what an ANA actually is, we can now start to approach the subject of clinical significance AND when it is appropriate to test someone for it.

The problem with the ANA is that it can be found in normal healthy people.

  • ANA 1:40 is found in 20 – 30% of healthy people
  • ANA 1:80 is found in 10 – 15% of healthy people
  • ANA 1:160 is found in 5% of healthy people
  • ANA 1:320 is found in 3% of healthy people
  • ANA can be positive in 5 – 25% of healthy people with a family member suffering from lupus
  • ANA can be positive in up to 70% of people aged above 70 years

To complicate things even more, an ANA can be present in someone that is about to develop an autoimmune disease… UP TO 10 YEARS before they actually develop the disease.  It can be positive in people suffering from cancer, people suffering from infections like tuberculosis, HIV, hepatitis C, mononucleosis etc.  It can even be positive when people are taking certain medications.  Not terribly not helpful right?

Bad example

So someone runs an ANA just because and it’s positive.

  1. Does it mean anything?
  2. Is the person one of those healthy normal individuals that has a positive ANA?
  3. Is the person going to develop an autoimmune disease in the future?

In this scenario, I would say that this test is of low clinical significance because it was obtained without purpose.  Because so many people that are completely healthy have an ANA, the test should only be run if a person is manifesting a symptom or better yet, multiple symptoms that are suggestive of an autoimmune disease like lupus, Sjögren’s syndrome, systemic sclerosis, mixed connective tissue disease, etc.  In that situation, it is helping answer a question.

Good example

If you’ve read my previous post, 8 important warning signs of scleroderma, you’ll remember that Raynaud’s phenomenon is an important red flag for scleroderma.  The vast majority of people suffering from Raynaud’s has no underlying autoimmune disease.  A small proportion does.  This is the perfect scenario, where an ANA would be useful.  If the ANA is negative, the person likely will NOT develop an autoimmune disease.  If the ANA is positive, then the person it at high risk of developing an autoimmune disease like scleroderma.  This person should be monitored more closely and probably have some follow-up blood tests.

Let’s wrap things up

Ultimately it all boils down to this simple fact: doctors treat people not numbers.

As a physician I care about symptoms and signs way more than unreliable lab tests.  Don’t get me wrong, these tests are important.  For example, over 99% of people suffering from systemic lupus erythematosus have a positive ANA.  It’s pretty much safe to say that if someone tests negative for ANA, they likely don’t have lupus.  FYI that other less than 1% usually has a positive SSA, they have a problem with their complement system, or they have a lot of protein in their urine (nephrotic syndrome).

I hope I’ve helped you better understand the elusive and mysterious ANA.  Again, this information does not constitute medical advice.  If you’ve tested positive for an ANA and have more questions, I highly encourage you to speak with your physician or local rheumatologist.  And remember, symptoms, symptoms, symptoms.

References

Rheumatology Secrets 3rd edition

 

Featured When to see a rheumatologist

8 important warning signs of scleroderma

November 28, 2016
Scleroderma is an autoimmune disease that can cause fibrosis of skin and internal organs. Early diagnosis is very important. Read on to learn more!

If I had to pick one autoimmune condition, which causes chills to run down one’s spine, I pick scleroderma.  The medical name for this condition is systemic sclerosis.  In a nutshell, systemic sclerosis is an autoimmune disease which causes inflammation in small blood vessels, which eventually can cause hardening of the skin and other major organs.

I quick Google search of scleroderma will inevitably present you with a horror show of images and stories from sufferers of this condition.

Yes, scleroderma is a terrible disease, but it’s also a terribly heterogeneous disease meaning that no two cases of scleroderma are the same.  There are mild cases and there are life-threatening cases.

Identification of early disease is probably one of the most important determinants of prognosis.  Well actually, it’s a little more complicated than that, but it is the one aspect that you can control:  The knowledge to know when to ask.

Types of Scleroderma

This is how rheumatologists breakdown scleroderma:

Classification of scleroderma

 

Basically, systemic sclerosis is when the disease affects the skin and internal organs and localized scleroderma is when it only involves the skin.  A lot of rheumatologists, included yours truly, believe that localized scleroderma and systemic sclerosis are actually two completely different diseases.

I’m going to concentrate on systemic sclerosis going forward.

Now we’re left with scleroderma sine scleroderma, limited systemic sclerosis, and diffuse systemic sclerosis.  Scleroderma sine scleroderma is systemic sclerosis involving the organs but not involving the skin.  This is super rare.

People that have limited systemic sclerosis have hardening of the skin that does not go past the elbows or knees.  They also tend to NOT have kidney involvement or inflammation of the lungs.  The disease course usually is insidious and sometimes is very difficult to detect, particularly during a 15 minute doctor’s appointment.

The last type is called diffuse systemic sclerosis.  It’s important to detect REALLY fast because it can progress quickly, because it can be deadly, and people simply do better when they’re treated early. People suffering from this type of scleroderma can have whole body hardening and are more prone to develop lung inflammation and kidney involvement.

Raynaud’s phenomenon

Almost everyone with any form of systemic sclerosis has something called Raynaud’s and esophageal reflux.  They also tend to appear early during the disease process, so these two symptoms are important to watch out for.

They say a picture is worth a thousand words.  Here’s an example of Raynaud’s… not the most dramatic example but that’s kind of the point.

This is a nice example of Raynaud's phenomenon.  Sometimes the finger can be white, like the pinky, and sometimes it can look dusky

 

Raynaud’s can involve your fingers and your toes.  Exposure to cold can cause it as well as a rapid change in temperature, and stress.  Raynaud’s is very common in women and for the most part is annoying but nothing serious.  The picture above is actually my hand.  This has been going on since my teens.  Let me tell you, I grew up in Canada.  Shoveling snow was kind of brutal.

About 15% of women have primary Raynaud’s (i.e., Raynaud’s without any underlying autoimmune condition).  Primary Raynaud’s typically first appears during one’s teens or early adulthood.  People with scleroderma tend to develop it later in life and  the intensity is A LOT more severe.  Sometimes the skin can become so ischemic (poor circulation) that it can cause an ulcer.  I have a lot of patients whom I’ve diagnosed with systemic sclerosis that told me that they thought that they had purple fingers because they were getting old…  This is NOT part of the normal aging process.

  1. Onset of Raynaud’s at a later stage in life.
  2. Raynaud’s complicated by ulcers.

Heartburn

Another symptom found in almost all people suffering from systemic sclerosis is heartburn.  This can present as chest pain, burning pain up your esophagus, nighttime cough, an acid taste in your mouth in the morning.  Sometimes people may have difficulty swallowing food and water.  Now, a lot of people have heartburn.  Just because you have heartburn, does not mean you have scleroderma.  You have to look at the entire picture.

  1. Heartburn
  2. Difficulty swallowing

Other common symptoms

Here is a list of other symptoms to watch out for:

  1. Puffy fingers, VERY high yield symptom
  2. Red spots all over your face, chest, and/or palms
  3. Hardening of the skin
  4. Shortness of breath with exercise

 

8 warning signs you may have scleroderma

Conclusion

There are a lot more symptoms that I haven’t gone over.  But sometimes less is more.  If you can remember these 8 warning signs, you have a really good chance of detecting early disease on your own, and maybe even save your life or the life of a loved one.  Having more than one of these symptoms should prompt you to consult a rheumatologist for further evaluation and testing.

For more information, I highly urge you to visit the Scleroderma Foundation website. They provide useful information about scleroderma for both the newly diagnosed and those that have had the disease for a long time.  They’re also involved research and patient advocacy.  Needless to say, I highly recommend them!

If you want to learn more about Raynaud’s phenomenon and ways how to treat it, read on.

References

Rheumatology Secrets 3rd edition

van den Hoogen F, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013 Nov;72(11):1747-55.

Minier T, et al. Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicenter study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis. Ann Rheum Dis. 2014 Dec;73(12):2087-93.

Scleroderma Foundation: http://www.scleroderma.org/site/PageServer#.WTC56WjytPY

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