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rheumatology

RheumDoctor Learning Center

RheumDoctor Learning Center: What is the microbiome?

May 17, 2017
How the microbiome affects the immune system

The microbiome refers to the combined genetic material of a group of microorganisms found in a certain body part such as the gut, respiratory tract, skin, or genitourinary system.

Symbiosis refers to a relationship between organisms that are beneficial for one another.

Dysbiosis refers to an imbalance of different microorganisms.  It is the opposite of a state of symbiosis.

How the microbiome and autoimmune diseases relate?

There appears to be an association between autoimmune dieaseses and dysbiosis, such as inflammatory bowel disease, spondyloarthritis, psoriasis, and rheumatoid arthritis.  It is still unclear whether autoimmune diseases cause dysbiosis or whether dysbiosis causes autoimmune diseases, let alone how we can use this information to treat and prevent autoimmune diseases.

Ultimately we need more research.  We live in interesting times!  Please leave your comments below!

References

National Human Genome Research Institute

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 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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Diseases and Conditions

Will I get osteonecrosis of the jaw if I take medications for osteoporosis?

April 12, 2017
Will I get osteonecrosis of the jaw if I take medications for osteoporosis?

Believe it or not, our bones are alive. Bones, in our bodies, are constantly renewing just like how our skin is constantly turning over. Our body’s ability to constantly build and breakdown bone is what allows us to grow and heal. This normal bone process over time results in our bones to get slightly thicker, however, we reach peak bone density in early adulthood.  As we age we gradually start to lose bone though.  Reduced bone mass puts us at risk for fractures which can be prevented by treatment.  It’s important to regularly perform weight-bearing exercise to prevent osteoporosis but sometimes it’s just not enough.  One of our best treatments (a group of drugs called bisphosphonates) slows the breakdown of bone and reduces the risk of a fracture, which is exactly what we want when treating osteoporosis.

What is Osteoporosis?

Osteoporosis is a disease in which bone density and quality are reduced, which means our bones become more porous and fragile, increasing the risk of fractures greatly. However, this bone loss occurs silently. Often there are no symptoms you would experience until your first fracture. It’s estimated that 200 million people worldwide suffer from osteoporosis. In the United States and in Europe, about 30% of all postmenopausal women have osteoporosis, and even worse at least 40% of these women will sustain one or more fragility fractures in their remaining lifetime.

But it is important not to forget that men suffer as well from osteoporosis.1

What is Osteonecrosis of the Jaw?

Exposed bone, in our mouths, that has persisted for more than 8 weeks. If a section of bone is fractured and does not heal it can cause blood flow to the bone to be interrupted causing bone death.

What Type of Treatment for Osteoporosis is related to Osteonecrosis of the Jaw?

Bisphosphonates work very well at slowing down the breakdown of bone which results in an increase in the density of bone. They have FDA approved indications for the treatment and prevention of post-menopausal osteoporosis, osteoporosis in men, and glucocorticoid (steroid) induced-osteoporosis. All bisphosphonates on the market have demonstrated reductions in vertebrae fractures and the majority of bisphosphonates show additional reduction in non-vertebral and hip fractures as well.

Bisphosphonates include: alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), zoledronic acid (Reclast)

Such strong inhibition of bone breakdown may theoretically lead to an accumulation of microdamage to the bone which might compromise bone strength or delay fracture healing. However, we have seen, from studying the bones of women on long-term bisphosphonates that there is no increased microdamage, and clinical trials of bisphosphonates did not show evidence of altered healing.2

What are Risk Factors for Osteonecrosis of the Jaw for Patients?

  • Drug-related risk factors
    • Bisphosphonate potency (oral therapies less potent than intravenous)
    • Duration of bisphosphonate treatment
  • Individual risk factors
    • Dental surgery
    • Concomitant oral disease
    • Periodontal disease
    • Ill-fitted dental prosthesis
  • Demographic factors
    • Genetic factors
  • Aggravating factors
    • Heavy smoking
    • Infection

What is the Real Risk of Osteonecrosis?

Osteonecrosis of the jaw (ONJ) is an extremely rare adverse event for patients taking bisphosphonates for osteoporosis.  Reports of bisphosphonate induced ONJ date back to the early 2000’s.  Reviews of current data support that up to 80% of ONJ cases occurred in patients with various cancers. These patients were also treated for a long period of time with high-dose injectable bisphosphonates. It is important to note that these doses were 10x higher than doses used to treat osteoporosis.3

Cases, of ONJ in osteoporotic patients, are extremely rare – not one case was found in more than 3000 patients participating in the clinical trials with zoledronic acid and alendronate. And no causal link between ONJ and bisphosphonate therapy, in these patients, has been convincingly demonstrated.4  

Although there are limitations to all studies, based on this information, the risk of ONJ in patients treated with bisphosphonates for osteoporosis is very low.

What does the American Dental Association Recommend?4

  • Routine Dental Care
  • Not modifying dental care solely because of bisphosphonates
  • Recommend AGAINST discontinuing bisphosphonates just before dental procedures

Conclusion

You should not stop taking your osteoporosis medication without talking to your medical provider. Osteoporosis is a serious but very treatable medical condition. The risk of fractures in people suffering from osteoporosis is very real and serious, while the risk of bisphosphonate-induced osteonecrosis of the jaw is rare. Also, there are  steps you and your doctor can take to help further reduce your risk by ensuring good dental hygiene and  preventive dental checkups  before starting and during treatment with these medications.    

Remember it’s always about benefit versus risk!

Author: Amy R. DeGennaro, 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. International Osteoporosis Foundation. Available at:  iofbonehealth.org
  2. Chapurlat RD, Arlot M, Burt-Pichat B, Chavassieux P, Roux JP, Portero-Muzy N, Delmas PD. Microcrack frequency and bone remodeling in postmenopausal osteoporotic women on long-term bisphosphonates: a bone biopsy study. J Bone Miner Res. 2007; 22:1502-1509.
  3. Hough FS, Brown SL, Cassim B, Davey MR. The safety of osteoporosis medication. South African Medical Journal. 2014;104.4: p279.
  4. Florence R, Allen S, Benedict L, Compo R, Jensen A, Kalogeropoulou D, Kearns A, Larson S, Mallen E, O’Day K, Peltier A, Webb B. Institute for Clinical Systems Improvement. Diagnosis and Treatment of Osteoporosis.  Updated July 2013.

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.

Diseases and Conditions

What do you mean by weight-bearing exercise?

March 22, 2017

Rheumatology primarily, and thankfully, deals with rare conditions with a few notable exceptions.  Osteoporosis being one of those.  According to the CDC

Percent of men 50 years of age and over with osteoporosis of the femur neck or lumbar spine: 4%

Percent of women 50 years of age and over with osteoporosis of the femur neck or lumbar spine: 16%

That’s a lot of people.  It’s also important note, that post-menopausal women are not the only ones that develop osteoporosis.  Men do.  People with inflammatory diseases do.  People that have GI absorption problems also do as well as people that don’t move a whole lot.

What is osteoporosis?

Osteoporosis is a condition that is characterized by weakening of bone.  People that have osteoporosis don’t feel they have osteoporosis.  It’s painless and there are no symptoms, until that is, something very bad happens like a fracture.  Bone strength is determined by bone mass and bone quality.  Think of a tree branch.  Branch A just fell off a healthy tree.  There was a bad storm and it just fell.  Structurally it’s normal.  Now you try to break it in half.  It’s a bit difficult to do.  Now you have Branch B.  This branch fell off a termite infested tree.  It’s partially hollowed out, i.e., the “wood” mass is significantly lower.  You try to break Branch B in half…easy peasy.  Osteoporosis = bone like Branch B.  Minor trauma in osteoporotic bone can result in a fracture.

Risk factors for osteoporosis

The next question is what are some of the risk factors that predispose someone to develop osteoporosis.  The good news is that some of these risk factors can be modified.  The bad news is that some risk factors cannot.

Things you CAN’T change

  • Advanced age
  • Ethnicity (white and Asian)
  • Early menopause
  • Slender build (< 127lbs)
  • Maternal history of hip fragility fracture
  • Certain medical conditions

Things you CAN change

  • Low calcium intake
  • Low vitamin D intake
  • Estrogen deficiency
  • Sedentary lifestyle
  • Cigarette smoking
  • Alcohol excess ( > 2 drinks/day)
  • Caffeine excess (> 2 servings/day)
  • Certain medications

Medical conditions

  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Lupus
  • Hyperthyroidism
  • Hyperparathyroidism
  • Alcoholism
  • Eating disorders
  • Inflammatory bowel disease
  • History of gastric bypass
  • Celiac disease
  • Renal failure
  • Multiple myeloma

There are a lot more conditions, but this is a quick list of the common ones.

Medications

  • Steroids!!! Like prednisone, methylprednisolone, dexamethasone, etc.
  • Excess thyroid meds
  • SSRIs
  • Proton pump inhibitors, used for heartburn

Before making any changes with your meds, please talk with your doctor. 

How to measure bone density?

Bone density is measured using dual energy x-ray absorptiometry (DEXA).  Just say DEXA, the first word is way too long and complicated.  Sometimes bone density can be measured with a special type of CT or ultrasound but this is not typical and usually is reserved for unusual situations.

The body parts that are typically measured are the lumbar spine, the hip, the femoral neck, and the forearm.  Sometimes the heel is also included.  These areas are best at predicting future fractures, which when you think about it, is what we’re trying to do: Prevent future fractures.

Typically, DEXAs are repeated every two years.  Again, there are some exceptions where DEXAs may be obtained more frequently.  For example, if I have a patient on a “boat-load” of steroids for systemic vasculitis for months and months on end, I may want to repeat the DEXA annually.

Why is it important to treat osteoporosis?

The answer to this question is very simple.  Prevention of fractures.  Other than the fact that fractures are incredibly uncomfortable, multiple studies have shown that fragility fractures particularly hip fractures, increase the risk of dying…  Yes you heard me, dying.  A recent article found that the one year risk of death was 23.6% after sustaining a hip fracture.  This finding is in line with most of the literature.  I don’t know about you but I don’t like these odds.

How to increase bone density?

The answer to this question is not simple.  The simple answer is eat a healthy diet, spend some time in the sun, if you smoke stop, supplement with calcium and vitamin D, regularly perform weight-bearing exercise, and medications.  The problem I have with this advice is that for the most part it is extraordinarily vague, except for the medication bit which will be covered in future posts.

What is weight-bearing exercise?

I’d like to focus on weight-bearing exercise, more specifically, what constitutes weight-bearing exercise.  I get this question a lot.

Before answering, “what is weight-bearing exercise”, we need to know what is NOT weight-bearing exercise.

Swimming is NOT weight-bearing exercise.

Cycling is NOT weight-bearing exercise.

Rowing is NOT weight-bearing exercise.

Don’t get me wrong, these exercises are excellent exercises for cardiovascular health, but they won’t help improve bone mass.  Weight-bearing exercises refers to exercises where you need to move your body against gravity.  These exercises can then be classified into high-impact and low-impact.  High-impact activities are better at building bone density but everyone has their own limits.  If you have severe osteoarthritis you may not be physically capable of performing high-impact activities.  Safety is a concern.  The National Osteoporosis Foundation has a nice list of activities.

High impact weight-bearing exercises are important but they are not the only factor in the equation.  Another major factor are falls, more specifically the prevention of falls.  Hip fractures almost always are directly caused by falls.  Having osteoporosis simply increases the risk of a fall that results in a fracture as opposed to a nasty bruise.  Some of the greatest fall risks include the following:

  • Frailty
  • Visual impairment
  • Cognitive impairment
  • Problems with your legs, this includes osteoarthritis of the knees
  • A cluttered home environment
  • A previous fall within the past 6 months.  This is actually number one on the list.

To help prevent falls, it’s important to try to correct some of the above.  It’s also important to perform activities that will help build muscle strength, balance, and mobility.  Most senior citizen exercise classes like the ones offered by the Silver Sneakers Program, focus on these types of exercises.

How much activity is necessary?

Again, this is difficult to quantify.

A recent Japanese study measured the number of steps per day continuously for 5 years and measured the bone density of participants’ heel on an annual basis.  They also measured the intensity of the activity.  After controlling for baseline density, age, and body mass, they found that bone health was optimal in elderly people who take at least 7000 to 8000 steps per day and/or spend at least 15-20 minutes per day at moderate activity.

It’s important to note that these people did not necessarily go to the gym.  Steps per day can be achieved in numerous natural different ways.  Blue Zone founder Dan Buettner has it as number #1 on the Power 9® list, MOVE NATURALLY.  If you’ve read some of my previous posts or actually heard me in clinic, you’ll know that I’m a huge fan of the Blue Zone Project.  We don’t need fancy supplements or gym memberships to achieve optimal health.  The following are a few examples on how to move naturally.

  • Walk, walk, walk.  Avoid using your car.
  • If you need to use your car, park further away.
  • Using stairs as much a possible, don’t use the escalator.
  • Start gardening.
  • Get rid of mechanical conveniences in the house.  I love my snow blower, but it has to go.

I hope that this has helped you.  If you retain only one thing, MOVE NATURALLY.  This is the secret to optimal bone health.

 

Disclaimer: the abovementioned information does not constitute medical advice.  Every case is unique.  Please contact your local rheumatologist or your physician for more information. 

References

CDC Osteoporosis Statistics

Rheumatology Secrets, 3rd edition

Guerra MT, et al. One-year mortality of elderly patients with hip fracture surgically treated at a hospital in Southern Brazil. Rev Bras Ortop. 2016 Dec 7;52(1):17-23.

National Osteoporosis Foundation

Shephard RJ, et al. Objective longitudinal measures of physical activity and bone health in older Japanese: the Nakanojo Study. J Am Geriatr Soc. 2016 Dec 9. doi: 10.1111/jgs.14553. [Epub ahead of print]

 

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Overcoming Inflammation

Tips for family and friends for people living with rheumatoid arthritis

March 15, 2017

Last week I was listening to one of my patients describe their condition in a deeply emotional and revealing way.  He honestly caught me off guard.

He said, that he woke up one day, and felt like a blob.  Like a being without joints, without tendons, ligaments or structure.  He could not walk or move.  He did not feel human anymore.

He was describing Part I of Franz Kafka’s seminal work, The Metamorphosis.  For those who have not read this novella, The Metamorphosis is the story of Gregor, a travelling salesman, who wakes one morning to discover that he has transformed into an insect-like being.  There is no rhyme or reason for his transformation.  It did not happen because he was a bad person or because of something he did.  It simply just happened.  The story deals with his attempts to adjust to his new physical state and his attempts to cling onto his humanity.  It also deals with the transforming relationships he has with various members of his family.  First how some show empathy but then quickly this empathy transforms into a sense burden and then repulsion.

Sound familiar?

When you think about it, it’s kind of depressing, especially for those who suffer from chronic diseases such as rheumatoid arthritis.  In certain cases, it’s a reflection of reality.  One wakes up one day and learns that their body will not let them to do what they used to do.  In the case of rheumatoid arthritis, you didn’t do anything to cause it.  It just happened.  It’s not like you were smoking 3 packs of cigarettes a day for 20 years and then you get diagnosed with emphysema.  That’s called playing with fire.  With RA, it just happens.

So now you find yourself not being able to do what you used to do: do your job, support your family, play with your kids.  It’s not because of a lack of will, your body simply won’t let you… not that you should give up:)  Now you become a burden to your family.  Your relationships change.

Unlike Kafka, I personally refuse to believe that these relationships will inevitably sour.  Healthy relationships with your loved ones can you grow healthier physically, emotionally, and psychologically.

The following are 8 tips to help metamorphose relationships into healthy and supportive ones.  Please share with family and friends!

 

Learn as much as you can about your loved ones disease

Knowledge is power.  It’s easier to have empathy when you have a sense of what’s going on and also what to expect.

But don’t assume you know everything.  You don’t.

No one likes a know-it all.  Don’t assume that you know what your loved one is going through or how they feel.  You can’t learn that in a textbook or from an article.  Be supportive.

Be a good listener

Sometimes people simply need vent.  Listen for cues.

Be adaptable

Life is going to change whether you like it or not.  There’s going to be good days and there’s going to be bad days.  Being rigid about your expectations is not going to get you anywhere.  Be flexible.

Don’t be overprotective

Find balance.  Although you want to help your loved one as much as you can, you also don’t want to strip them of their independence and by being overprotective.

Open communication

Be open about your emotions and thoughts.  A healthy relationship is one free of passive aggressiveness.

Join a support group

There are many support groups out there.  Let me tell you, I’ve been there.  Not for RA though.  All of a sudden the person you love and depend on, gets diagnosed with this terrible disease.  And EVERYTHING changes.  There’s nothing worse than the deep sense of loneliness that comes along.  Support groups can help overcome the isolation.  Find a support group near you!

Unconditional love

Whatever life throws at us, we will deal with it together.  I promise not to scream at you because I’m having a bad day.  I promise not to blame you for the money problems we have now.  I love you, I will support, and advocate for you no matter what conditions.  This is unconditional love.

 

I hope this has been helpful. Please leave any comments below.  I’m interested in hearing your thoughts and experiences.

 

Diseases and Conditions

What are the risks vs. benefits of biologic therapy?

March 8, 2017

Some of you may recall one of my previous posts where I attempted to dispel some of the myths commonly associated methotrexate.  Don’t get me wrong, I frequently use methotrexate.  It is considered gold standard for the treatment of rheumatoid arthritis.  And this is despite the armada of new fancy medications coming onto the market.  The American College of Rheumatology doesn’t call it the gold standard for nothing.

But sometimes it isn’t enough.

It’s estimated that about 30% of people achieve either remission or very minimal disease activity with methotrexate alone.  That leaves the other 70%.  Maybe this includes you?  In this situation, your rheumatologist may either recommend you to combine methotrexate with another conventional disease modifying anti-rheumatic drug (DMARD) or either to combine it with a biologic DMARD.  The decision is very complex and will vary from person-to-person and from rheumatologist-to-rheumatologist.  Were there issues with the ability to tolerate the medication, allergies, other medical conditions, insurance coverage, safety profile concerns, etc?  And then there’s just style.

DMARDs

In the best of situations, ALL people diagnosed with rheumatoid arthritis should be started on a DMARD as quickly as possible.  For those who don’t really know me, the tone of this statement is very uncharacteristic of me.  I loathe dogma and authoritarian statements in general.  But when it comes to DMARDs and rheumatoid arthritis, people that receive these medications as soon as possible do better and have less joint damage.  It’s important to achieve remission or have very minimal disease activity as soon as possible and as long as possible.

So what is a DMARD? For a medication to be considered a DMARD it has to change the course of the disease, for the better:), for at least one year.  There should be improvement in either physical function, decreased swelling, or slowing/prevention of joint damage.

To understand why your doctor may want to start a biologic medication, it’s important to understand what is meant by a conventional vs. a biologic DMARD.

I would say there are two main differences between conventional DMARDs and biologic DMARDs: mechanism of action and cost.  Conventional DMARDs do NOT directly target a specific type of inflammation.  Biologics do.  This means that biologics are a lot more molecular complex.  This also means that they are A LOT more expensive.  Even in countries like Canada, where the single payer system has the ability to negotiate prices with pharmaceutical companies, the price is still very high.  I could on and on with this subject, but I’ll leave that for another post.

Conventional DMARDs

  • Often used
    • Hydroxychloroquine
    • Methotrexate
    • Leflunomide
    • Sulfasalazine
  • Not really used
    • Azathioprine
    • Mycophenolate, sometimes used for rheumatoid arthritis affecting the lungs
    • Cyclophosphide, used for life or organ threatening disease
    • Cyclosporine
    • Gold injections

Biologic DMARDs

  • Tumor necrosis factor inhibitors
    • Etanercept
    • Adalimumab
    • Golimumab
    • Certolizumab pegol
    • Infliximab
  • Interleukin-6 inhibitors
    • Tocilizumab
  • Co-stimulation inhibitors
    • Abatacept
  • JAK inhibitors
    • Tofacitinib
  • B cell depletion
    • Rituximab

There are other medications that are coming down the pipeline, but these are the ones that are FDA approved and commercially available for the treatment of rheumatoid arthritis.  There are other biologic medications like belimumab, apremilast, ustekinumab, and secukinumab that are used for other diseases like systemic lupus erythmatosus, psoriatic arthritis, and ankylosing spondylitis.

Triple therapy vs. methotrexate + biologic

Generally triple therapy refers to the simultaneous use of methotrexate + sulfasalazine + hydroxychloroquine for the treatment of rheumatoid arthritis.  A Cochrane meta-analysis recently found that triple therapy typically is just as effective as methotrexate + a biologic or tofacitinib alone.  So why is your doctor proposing going to a biologic medication instead of going to triple therapy?  It certainly would be cheaper.

This is where I would say is one of the potential benefits of biologics: the ability to tolerate treatment long-term.  Let’s put things into perspective.  When you take an antibiotic, you may end up with some GI discomfort, diarrhea, some nausea, etc.  You receive 7 days worth of treatment, the infection is gone, it usually takes a few more days for things to settle down, but then it’s done.  When it comes to the vast majority of rheumatic conditions like rheumatoid arthritis, some form of medication is consistently needed to keep the disease in remission. If you stop, the disease flares.  Don’t get me wrong, there are exceptions.  Sometimes the disease goes into permanent remission or “burns out”.  This is rare and definitely is not the rule.

The problem with triple therapy is that it tends to be very difficult to tolerate long-term.  Most people could tolerate a few weeks, but we’re talking years, decades, lifetime.  Many people stop one or more of the medications without telling their doctor, others take them sporadically.  Basically, there’s a lot of non-compliance with treatment when people receive triple therapy.

It isn’t necessarily because those people are irresponsible.  It’s that the medicines are making them feel sicker than their actual disease!

Simply put, biologics tend to be a lot easier to tolerate long-term and to bout SOME can be used as monotherapy i.e., you don’t need to combine with methotrexate.

Onset of action

I wouldn’t say that this is necessarily the most important factor when making a decision to go with a biologic instead of sticking to conventional DMARDs but I guess it could help tip the balance in certain situations.  In general biologic DMARDs tend to work a little more quickly that conventional.  This greatly varies from biologic-to-biologic.  Generally conventional DMARDs taking between 3 – 6 months to fully work.  It tends to be closer to the 3 month mark.  For most biologics it can take up to 3 months.  Certain ones like abatacept can take up to 6 months as well.

Cost

Most biologics cost over $ 1 100 per month.  Mind you, hardly anyone actually pays $ 1,100 per month.  Before starting a biologic medication, you doctor’s office will obtain authorization from your insurance company prior to prescribing the medication.  When the medication is authorized, your doctor will send it to your prescription mail-order company, and then it will be mailed to you.  Co-pays vary from $5 a script to a few hundred dollars in extreme cases.  It really depends on your insurance coverage.  It’s very important to keep your doctor but also your doctor’s medical secretary and if your doctor is extra lucky, your doctor’s patient advocate, appraised of all changes to your insurance.  It can mean the difference between a $5 co-pay and a second mortgage.  Most pharmaceutical companies have patient assistance programs.  Some are better than others… and some are better advertised than others.

Conventional DMARDs are a lot cheaper.  For example, methotrexate comes in 2.5 mg tablets.  20 tablets cost a little over $25.  This is the price if you had no insurance and were paying completely out of pocket.  Someone taking oral methotrexate will typical take between 24 to 40 tablets per month.  For most people this is doable even without any insurance.

Conversely, if you were receiving etanercept and had no insurance, your out of pocket cost would be about $3,500 per month.  Again, your doctor’s team will work to have the medication covered, but it’s still something to think about.

Method of delivery

This may be a non-issue for many people but it may be for some.  Most biologics need to either be injected or infused.  So far, only tofacitinib (rheumatoid arthritis) and apremilast (psoriatic arthritis) are taken orally.  There are pros and cons for both injections and infusions but generally, if your needle phobic, this may be a problem.  Infusions are time consuming because you need to come to the clinic to receive the infusion.  They typically last between an hour to half a day depending on the medication.  Some are dosed every month others every 8 weeks.  Rituximab is every 6 months but this is an exception.  Most injections are either given every week or every other week.  Some are a lot less frequent like ustekinumab, but again this is an exception.

Conversely, all the conventional DMARDs are oral except for cyclosphosphamide and gold.  I’ve never prescribe cyclophosphamide for rheumatoid arthritis… ever.  First, we simply do not encounter many people with life-threatening complications caused by rheumatoid arthritis anymore because the vast majority of people with the condition are treated with DMARDs very early into their disease.  Second, there are many other medications on the market that are a whole like better.  Don’t get me wrong, there are certain very serious indicated clinical situations.  Just wrote an order for it last week… my first in a year and it wasn’t for RA!

Infection risk

One of the big differences between conventional DMARDs and biologics is the infection risk.  Biologic medications generally are a lot more immunosuppressive than conventional DMARDs.  Again there are exceptions.  For example, abatacept is generally thought to have less of an infection risk.

I have to stress that this does not mean that people taking biologics get a ton of infections.  But it becomes extra important to keep up with routine vaccinations, adhere to proper hand washing, and try to stay away from high risk situations as much as possible.  It may also not be such a great idea to be on a biologic if you are prone to getting infections.  Let’s face it, no one wants 10 sinus infections in one year.  It also may not be such a great idea to be one some of these biologics if you have very serious lung problems.  I probably will try to avoid most biologics if someone has severe COPD requiring extra oxygen.  Pneumonia could be life-threatening in this situation.

Another important noteworthy point, certain biologics can re-activate dormant infections such as tuberculosis, hepatitis B+C, and zoster.  It’s important to screen for both tuberculosis and hepatitis B+C prior to initiation of therapy.   You may need to start therapy for these latent infection prior to treatment with biologics.  For zoster also known as shingles, you may benefit from the shot one month prior to treatment with biologics.  The shingles shot is a live vaccine and should NOT be given while taking a biologic medication.  Like I said, you need to wait a month.  Please contact your rheumatologist for more information.

Miscellaneous

There are a few other items of concern but these vary from medication to medication irrespective of whether that medication is a conventional DMARD or a biologic.  The following are items to consider when choosing the most appropriate medications.

  • History of hepatitis C
  • History of HIV
  • History of a demyelinating disease like multiple sclerosis
  • History of severe congestive heart failure
  • History of lymphoma or leukemia
  • History of melanoma
  • History of a solid cancer within the last 5 years (e.g., breast cancer)
  • History serious liver disease
  • History of a serious kidney disease
  • History of serious lung disease
  • History of serious diverticulitis or bowel perforation
  • History of gastric bypass surgery
  • History of macular degeneration
  • History of organ transplant
  • Allergy history
  • Current medications.  Are there any possible drug interactions? (e.g., azathioprine and allopurinol should not be combined)

Having one of these does NOT mean you cannot take any biologic medication safely.  It simply means that certain ones may not be such a good idea.  For example, tumor necrosis inhibitors should not be taken by people suffering from multiple sclerosis.

Conclusion

I hope this helps clarify a few concerns that you may have had regarding biologic medications.  Maybe I’ve caused you to think about things you had not thought about before?  Choosing the best course of therapy can be very complex.  There are so many things to think about and the down stream effects could be very serious.

Open communication and knowledge are key!

References

Rheumatology Secrets 3rd edition

Hazlewood GS, et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A network meta-analysis. Cochrane Database Syst Rev. 2016 Aug 29;(8):CD010227. doi: 10.1002/14651858.CD010227.pub2.

https://www.drugs.com/price-guide/methotrexate

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