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Guide to living with psoriatic arthritis: Part 1

September 26, 2017
Psoriatic arthritis is an autoimmune disease that not only affects skin, but also joints

In an earlier post I presented a guide to living with rheumatoid arthritis (RA).  That’s all good if you have RA, but what if your rheumatologist diagnosed you with psoriatic arthritis?  What’s psoriatic arthritis and how is it similar or dissimilar to RA?  This week I’ll present to you Part 1 of a Guide to living with psoriatic arthritis.  I’m going to present this as a three-part series.  Part 1 will cover the basics: what is psoriatic arthritis, the cause, risks, symptoms, diagnosis, and treatment.  In Part 2 I’ll cover prognosis, what to expect, diet and exercise.  In Part 3, I’ll be covering the financial side of psoriatic arthritis: How to get access to medications and how to navigate the complicated world of health insurance.

What is psoriatic arthritis?

Psoriatic arthritis (PsA) is a type of autoimmune inflammatory arthritis that afflicts people who suffer from psoriasis (PsO).  It’s estimated that about 26% of people who suffer from psoriasis will get psoriatic arthritis at one point during their lifetime.  Typically, people develop psoriasis first and then get the arthritis.  In some cases, people develop arthritis first and then get psoriasis but this is a lot less common.   Psoriatic arthritis is one of the more common causes of autoimmune arthritis affecting about 2 to 3% of the population.[1]

What is psoriasis and what are the different types of psoriasis?

Psoriasis is an autoimmune disease that affects the skin.  It typically involves the elbows, knees, and scalp, but you can find it in many other areas.  It typically causes itchiness, burning as well as a stinging sensation.  Psoriasis affects about 2% of African-Americans and affects about 3.6% of Caucasians.  Usually people develop it between the ages of 15 and 35, but it can also happen in very young children and older adults as well.

There are many different types of psoriasis and they are all associated with psoriatic arthritis.

  • Plaque psoriasis
  • Guttate psoriasis
  • Inverse psoriasis
  • Pustular psoriasis
  • Erythrodermic psoriasis (life-threatening type of psoriasis)

Please follow this link to learn more about psoriasis.[2]

What causes psoriatic arthritis?

Like most diseases in rheumatology, we’re not sure.  We do know that there’s a strong genetic and environmental part to psoriatic arthritis.  Here are some genetic associations.

  • HLA-Cw6 is associated with severe early onset skin psoriasis
  • HLA-B38 and HLA-B39 are associated with psoriatic arthritis
  • HLA-B27 is associated with psoriatic arthritis that affects the spine.

Although genes do play a part in psoriatic arthritis, most people who have psoriatic arthritis have no genetic risk factors.

The Koebner Phenomenon

Have you ever heard of the Koebner phenomenon?  This phenomenon describes a new skin lesion in an area where healthy skin was injured.  For example, let’s imagine that you have psoriasis.  A mosquito comes along and bites you, it itches, so you scratch.  Then, about 10 days later, you notice that you’ve developed psoriasis in the area you scratched.  That’s the Koebner phenomenon.[3]

Now try to imagine the Koebner phenomenon involving joints.  It’s thought that about 25% of people who get psoriatic arthritis develop the condition after trauma to a joint.  We call this the deep Koebner phenomenon.[4]

Ultimately, we still don’t know exactly why people develop psoriatic arthritis.  Our best guess like most autoimmune diseases, is that certain people are born with a predisposition to develop both psoriasis and psoriatic arthritis.  Then, something in the environment triggers the disease to “come online”.

Does everyone with psoriasis get psoriatic arthritis?

No.  A recent Japanese study tried to find certain risk factors that predispose patients with psoriasis to develop psoriatic arthritis.  First, they found that about 17% of people with psoriasis also had psoriatic arthritis.   Second, they found that people who had psoriasis involving their nails had a higher chance of having psoriatic arthritis: 29% (PsO) versus 62% (PsA).  Interestingly, they also found that people who had high uric acid levels also had a higher risk of having psoriatic arthritis 9% (PsO) versus 22% (PsA).[5]

As a side note, when uric acid levels are high, this increases the risk of gout.

How does psoriasis affect the nails?

Nail psoriasis is very common.  It ranges from about 50% to 87% of people who have psoriasis.  Now, nail psoriasis can present in many ways depending on the anatomic site of the psoriasis inside the nail.  First, a bit of anatomy.

Nail anatomy

 

The nail consists of the nail fold, the nail matrix, and the nail bed.  The nail fold is where the blood vessels supplying the nail come from.  They can be compromised in many diseases such as scleroderma.  The nail matrix is responsible for formation of the nail plate and the nail bed is responsible for attaching the nail plate firmly in place.

Anatomy of the nail

 

When psoriasis affects the nail matrix.  It can cause pitting, crumbling, white spots and red spots in the lunula.  When psoriasis affects the nail bed, it can cause splinter hemorrhages and splitting of the nail from the nail bed (onychyolysis).[6]  Please click the following link to learn more about nail psoriasis + pics.

Please note that none of the features of nail psoriasis are exclusive to psoriasis.  Other diseases can cause these, including:

  • Reactive arthritis
  • Alopecia areata
  • Chemical dermatitis
  • Pemphigus vulgaris.
  • Incontinentia pigmenti

How is psoriatic arthritis different from rheumatoid arthritis?

Although both psoriatic arthritis and rheumatoid arthritis are both autoimmune diseases that affect joints, they are both distinct diseases.  It isn’t simply because you have psoriasis and inflammation in your joints, that you have psoriatic arthritis. Many people with psoriasis have rheumatoid arthritis.  Psoriatic arthritis and rheumatoid arthritis have their own pathophysiology, epidemiology, and symptoms.  Although they do share many treatment options, they also have some medications tailor-made for them.

Here some of the main clinical differences between psoriatic arthritis and rheumatoid arthritis.

  Psoriatic arthritis Rheumatoid arthritis
Joint distribution Asymmetrical Symmetrical
Joint involvement DIP, dactylitis MCP, PIPs, wrists, and MTPs
Involvement of the spine Common Rare, involves the cervical spine
Labs* RF and CCP antibody negative RF and/or CCP antibody positive

* RF = rheumatoid factor, CCP = Cyclic citrullinated peptide antibodies

As you’ll see later on, it’s a lot more complicated that.  Many people presenting with psoriatic arthritis present almost exactly like rheumatoid arthritis.  Here were a few other features that favor a diagnosis of psoriatic arthritis.

  • Presence of nail pits
  • When there is inflammation of the distal interphalangeal joints (Tip of your finger) without any evidence of osteoarthritis
  • “Sausage digits” = dactylitis. This happens when the tendons that supply of the fingers and toes get inflamed.
  • Any inflammation of tendons and ligaments, such as Achilles tendinitis and plantar fasciitis.
  • When there is a family history of psoriasis or psoriatic arthritis, particularly in a first-degree relative. That mom, dad, kids and siblings.
  • The spine is involved.

What are the symptoms of psoriatic arthritis?

If you’re experiencing joint pain and you have a history of psoriasis, particularly psoriasis that involves your nails, you need to think about psoriatic arthritis.  So what do I mean by joint pain?  When it comes to joint pain, what I really mean is, autoimmune or more specifically, inflammatory joint pain.

Psoriatic arthritis can affect almost any joint: knuckles, wrists, toes, knees, shoulders, elbows, hips, and the spine.  Mechanical joint pain is very different from inflammatory joint pain.  Let me explain.

Peripheral inflammatory joint pain

Peripheral joints include all joints except those involving the spine.  When there is inflammation in a peripheral joint, typically people experience pain, swelling, and stiffness, particularly in the morning that lasts at least an hour.  Sometimes they do see some redness and the joints may feel hot at times.  Often times, people also feel a lot more tired than usual, and they can even run low-grade fevers.

Axial inflammatory joint pain

Axial joints are those that involve the spine.  Inflammation involving the back causes symptoms that are very different from your usual mechanical back pain.  Here are some of the following key characteristics:

  • Back pain present for more than three months.
  • Pain improves with exercise.
  • Pain improves with anti-inflammatory medications like naproxen or ibuprofen.
  • Rest usually worsens the pain.
  • Back pain that wakes you up during the second half of the night.
  • Pain and prolonged stiffness in the morning, typically lasting more than an hour.
  • Alternating deep buttock pain.

Enthesitis

Enthesitis means inflammation of connective tissue that attaches to bones.  These include tendons, ligaments, and bursae.  Most cases of enthesitis are caused by injury or overuse.  Think of a marathon runner with Achilles tendinitis or a tennis player with tennis elbow.  In psoriatic arthritis, the immune system attacks these connection points.  So you can have someone who leads a fairly sedentary life with Achilles tendinitis on both feet, runner’s knee, and plantar fasciitis happening all at once, for no good reason.  Not a pleasant experience.

Uveitis

Uveitis is a general term that we use to describe a group of inflammatory diseases that cause inflammation in many parts of the eye: uvea, lens, retina, optic nerve, and the vitreous.  Depending on where the inflammation is happening, your ophthalmologist may describe it as anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis.

Uveitis is associated with many diseases including psoriasis and psoriatic arthritis.  Sometimes uveitis is the first manifestation of psoriatic arthritis.  This is why I’ve included this topic here, even though technically it isn’t arthritis.  It’s important to know and keep in the back of your mind.[7]

Patterns of disease

Just like rheumatoid arthritis, psoriatic arthritis, can manifest in many ways.  For those of you who want to get really technical, I’ve included a table describing the most common ways psoriatic arthritis presents.

Subtype Percentage Typical joints
Asymmetric oligoarticular* disease 15-20% DIP joints and PIP joints of the hands and feet.  MCP joints, MTP joints, knees, hips, and ankles.#
Predominant DIP involvement 2-5% DIP joints
Arthritis mutilans$ 5% DIP and PIP joints
Polyarthritis! “rheumatoid–like” 50-60% MCP joints, PIP joints, and wrists.
Axial involvement only (spine) 2-5% Sacroiliac joints, vertebral
Enthesitis predominant Tendons and ligaments[8]

* oligoarticular = 2 – 4 joints

# DIP = distal interphalangeal joints, PIP = proximal interphalangeal joints, MCP = metacarpophalangeal joints, MTP = metatarsophalangeal joints

$ Mutilans = severely deformed

! Polyarthritis = 5 or more joints involved

How is psoriatic arthritis diagnosed?

We currently use the CASPAR criteria to make the diagnosis of psoriatic arthritis.  You need three points to get the diagnosis because having 3 or more points has a 99% specificity and 92% sensitivity for the diagnosis of psoriatic arthritis.  Obviously, there are exceptions as the CASPAR criteria are predominantly used for research purposes.

As you can see, you don’t need to have psoriasis to get a diagnosis of psoriatic arthritis.  I know this sounds counterintuitive.

CASPAR classification criteria

  • Evidence of psoriasis (current, past, family)
    • 2 points if current
    • 1 point if history of psoriasis or family history
  • Psoriatic nail dystrophy = 1 point
  • Negative rheumatoid factor = 1 point
  • Dactylitis = 1 point
  • X-ray changes = 1 point

HLA-B*27 antigen

Unlike rheumatoid arthritis, we do not have blood tests to help with the diagnosis of psoriatic arthritis.  At times, your rheumatologist may order something called a HLA-B*27 test.

HLA-B*27 is a genetic test. The majority of people who have a positive HLA-B*27 are perfectly healthy. HOWEVER, having a positive HLA-B*27 can put you at increased risk of developing what we call spondyloarthritis-associated diseases. This is a family of autoimmune diseases. They include:

  • Ankylosing spondylitis, now called axial spondylitis
  • Peripheral spondyloarthritis
  • Reactive arthritis
  • Psoriasis
  • Psoriatic arthritis
  • Uveitis
  • Crohn’s disease
  • Ulcerative colitis

Not every person with psoriatic arthritis will test positive for HLA-B*27, however, those that do, have a higher risk of having axial involvement.[9]  This is important to know, because it may affect the medication your rheumatologist recommends.

Is there a cure for psoriatic arthritis?

The simple answer to this question is no.  Psoriatic arthritis is a chronic, lifelong disease.  Although there is no cure for psoriatic arthritis, there are many medications that can help halt or slow down progression: disease modifying anti-rheumatic drugs (DMARD).

Cardiovascular disease and psoriatic arthritis

In recent years, scientists have found an association between cardiovascular disease and many autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriasis, Crohn’s disease, ulcerative colitis, and psoriatic arthritis.  Basically, people who suffer from psoriatic arthritis have a higher risk of developing cardiovascular disease.[10][11]  [12] Unfortunately, they also tend to have more traditional cardiovascular risk factors like high blood pressure, high cholesterol, and diabetes.  [13]On the upside, effective treatment of psoriatic arthritis can decrease this risk.[14]

How is psoriatic arthritis treated?

Like rheumatoid arthritis, psoriatic arthritis is treated with disease modifying anti-rheumatic drugs (DMARDs). These medications are designed to stop or slow down the progression of psoriatic arthritis by targeting the faulty part of the immune system.  Without treatment, psoriatic arthritis, can cause permanent damage to joints, tendons and ligaments leading to functional impairment and a decrease in quality of life.

Which DMARDs are used to treat psoriatic arthritis?

The following are some of the medications that doctors often use to treat psoriatic arthritis.  Your doctor will recommend certain treatments based on the involved joints and organs, as well as severity, allergies, and other medical conditions you may have.

I’ve broken down the different medications into the following broad categories.

Nonsteroidal anti-inflammatory drugs

  • Ibuprofen
  • Meloxicam
  • Naproxen
  • Sulindac
  • Etodolac
  • Diclofenac
  • Indomethacin
  • Celecoxib

Conventional DMARDs

  • Hydroxychloroquine (Plaquenil) – caution as this medication may make psoriasis flare
  • Methotrexate
  • Leflunomide (Arava)
  • Sulfasalazine
  • Azathioprine – rarely used for psoriatic arthritis

Biologics

Tumor necrosis factor – alpha (TNF-alpha) inhibitors

  • Certolizumab pegol (Cimzia)
  • Etanercept (Enbrel)
  • Adalimumab (Humira)
  • Infliximab (Remicade)
  • Golimumab (Simponi)

Interleukin 12 and 23 inhibitors

  • Ustekinumab (Stelara)

Interleukin 17 inhibitors

  • Secukinumab (Cosentyx
  • Brodalumab (Siliq) – not FDA approved for PsA
  • Ixekizumab (Taltz) – not FDA approved for PsA

T cell inhibitors

  • Abatacept

Interleukin 23 inhibitors

  • Guselkumab

Phosphodiesterase 4 inhibitors

  • Apremilast (Otezla)

To read more about treatment for psoriatic arthritis.  Please follow this link.

Biosimilars

Here in the US, we are starting to see biosimilar medications. 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.

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

No.  Psoriatic 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 psoriatic arthritis will likely come back.  Psoriatic arthritis subsides spontaneously in a VERY small subset of people.

If your medication is making you feel sick, talk to your rheumatologist.  They truly have your best interest at mind and they want to find the best treatment for you.

Do not stop your medications without first consulting your rheumatologist.

Next steps

Let’s recap what we’ve learned today.

  • Psoriatic arthritis is an inflammatory arthritis that affects about 26% of people that suffer from psoriasis and affects about 2 to 3% of the population.
  • We know that there is a strong genetic link and environmental component to psoriatic arthritis, but the majority of cases happen spontaneously.
  • People with nail psoriasis have a higher risk of getting psoriatic arthritis.
  • The Koebner phenomenon describes the appearance of a new skin lesion in an area where healthy skin was injured. The same thing can happen in joints.  This is  the deep Koebner phenomenon.
  • Psoriatic arthritis can present in many ways. It can cause peripheral inflammatory arthritis, axial inflammatory arthritis, enthesitis, and uveitis.
  • Doctors use the CASPAR criteria to help make a diagnosis of psoriatic arthritis. You need three points to get the diagnosis because having 3 or more points has a 99% specificity and 92% sensitivity for the diagnosis of psoriatic arthritis.
  • There are no specific tests help make the diagnosis of psoriatic arthritis, however, people that test positive for HLA-B*27 have a higher chance of having psoriatic arthritis in their spine.
  • People with psoriatic arthritis have a higher risk of having cardiovascular disease but treatment can possibly decrease that risk.
  • Psoriatic arthritis is treated with disease modifying anti-rheumatic drugs.

In part 2 of the Guide to living with psoriatic arthritis, I’ll be covering topics such as natural treatments for nail psoriasis and psoriatic arthritis, the FODMAP diet, how to exercise, and strategies on how to reduce stress.   In part 3 of the Guide to living with psoriatic arthritis, I’ll be covering the financial aspect of psoriatic arthritis most notably, health insurance coverage and the prior authorization process for expensive medications.

Stay tuned and please leave your comments below!

Please follow this link to request a rheumatology consultation.

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.

References

Sick woman main areas of the human body affected by psoriasis: By ann131313 via Shutterstock

Nail anatomy by  Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

[1] Rheumatology secrets, 3rd edition

[2] https://www.psoriasis.org/about-psoriasis

[3] https://www.dermnetnz.org/topics/the-koebner-phenomenon/

[4] Rheumatology secrets, 3rd edition

[5] Tsuruta N, Imaguku S, Narisawa Y.  Hyperuricemia is an independent risk factor for psoriatic arthritis in psoriatic patients. J Dermatol. 2017 Jul 10. doi: 10.1111/1346-8138.13968. [Epub ahead of print]

[6] Manhart R, Rich P. Nail psoriasis. Clin Exp Rheumatol. 2015 Sep-Oct;33(5 Suppl 93):S7-13.

[7] https://nei.nih.gov/health/uveitis/uveitis

[8] Rheumatology Secrets, third edition

[9] Jadon DR, et al. Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis. Ann Rheum Dis. 2017 Apr;76(4):701-707. doi: 10.1136/annrheumdis-2016-209853. Epub 2016 Dec 2.

[10] Ozkan SG, Yzisiz H. Gokbelen YA, Borlu F, Yazisiz V.  Prevalence of metabolic syndrome and degree of cardiovascular disease risk in patients with psoriatic arthritis. Eur J Rheumatol. 2017 Mar;4(1):40-45. doi: 10.5152/eurjrheum.2017.16052. Epub 2017 Mar 1.

[11] Fernandez-Gutierrez B, et al. Cardiovascular disease in immune-mediated inflammatory diseases: A cross-sectional analysis of 6 cohorts. Medicine (Baltimore). 2017 Jun;96(26):e7308. doi: 10.1097/MD.0000000000007308.

[12] Castaneda S, et al. Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attending rheumatology clinics: Baseline data of the CARMA project. Semin Arthritis Rheum. 2015 Jun;44(6):618-26. doi: 10.1016/j.semarthrit.2014.12.002. Epub 2014 Dec 25.

[13] Jafri K, Bartels CM, Shin D, Gelfand JM, Ogdie A.  Incidence and management of cardiovascular risk factors in psoriatic arthritis and rheumatoid arthritis: a population-based study. Arthritis Care Res (Hoboken). 2017 Jan;69(1):51-57. doi: 10.1002/acr.23094. Epub 2016 Nov 28.

[14] Agca R, Heslinga M, Kneepkens EL, van Dongen C, Nurmohamed MT. The effects of five-year etanercept therapy on cardiovascular risk factors in patients with psoriatic arthritis. J Rheumatol. 2017 Jun 1. pii: jrheum.161418. doi: 10.3899/jrheum.161418. [Epub ahead of print]

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
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

Diseases and Conditions

10 frequently asked questions when starting methotrexate

February 22, 2017
Methotrexate is one of the mostly frequently prescribed medications in rheumatology. It has great joint-saving potential but also has a considerable list of potential side effects. In this week's edition of RheumDoctor, we address frequently asked questions when starting methotrexate.

Hands down, methotrexate is one of the most frequently prescribed medications in the field of rheumatology as it is the cornerstone medication for rheumatoid arthritis.  As a rheumatologist, I tend to classify time as, “the time before methotrexate” and “the time after methotrexate”.

Methotrexate was first reported by Sidney Farber in 1948 for the use of childhood leukemia.  By 1951, Gubner observed that people with rheumatoid arthritis and psoriasis improved while taking the medication and soon worsened after stopping it.  Unfortunately and fortunately, during this time Dr. Phillip Hench received a Nobel prize for the discovery of corticosteroids.  At that point, interest for methotrexate waned.  It’s only in the mid-1980’s that a renewed interest for this paradigm-shifting medication occurred.  The rest is history.

I don’t believe anyone can argue the significant benefits methotrexate can give.  The scientific evidence is overwhelming.  But it also boasts a considerable list of potential side effects.  In this week’s edition of RheumDoctor, I address frequently asked questions when starting methotrexate.

Before starting, the information below does not constitute medical advice.  Every person and every situation is unique.  Please address questions about your care with your rheumatologist.

1. Why do I have to take methotrexate?  I went online and it sounds dangerous.

Do an image Google search with the term “rheumatoid arthritis”.  Yep, not so pretty.  Remember when I said that I tend to classify time as, “the time before methotrexate” and “the time after methotrexate”.  There’s a pretty good chance that the people with the gnarly hands are the people who received methotrexate very late into their diagnosis.  Methotrexate is a disease modifying anti-rheumatic drug (DMARD).  What this means, is that it potentially halts the natural progression of rheumatoid arthritis.  If left untreated, rheumatoid arthritis causes joint deformities and permanent joint destruction.  Deformities can occur within 3 months of disease onset.  That’s fast!  Uncontrolled rheumatoid arthritis increases the risk of cardiovascular disease and can also directly affect major organs such as the lungs, eyes, and bone marrow.  Methotrexate has a good chance of preventing all the above.

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

2. Why do I have to take folic acid with methotrexate?

Methotrexate competitively inhibits dihydrofolate reductase (DHFR).  This is in turn decreases the amount of bioavailable folic acid in your body.  You need folic acid to make new cells.  What does this mean?  Side effects: mouth ulcers, hair loss, nausea, heartburn, abdominal pain, fatigue, anemia, liver problems.  By taking supplemental folic acid, you are trying to overwhelm the system with folic acid so that you don’t develop side effects.  It’s important to note, that if you take too much folic acid, it will negate the therapeutic benefits of your medication.

3. Why must I have bloods drawn on regular intervals while I’m taking methotrexate?

Simply put, safety. Before starting methotrexate you need to screen for hepatitis B and hepatitis C.  This isn’t personal, it’s just safe.  You will also need a chest x-ray done before starting the medication.  Methotrexate can cause you to develop lung nodules and rarely can cause inflammation of the lungs.  Basically, you want to make sure that everything is okay before starting the medication.  For example, if I find many lung nodules before doing anything, I’ll probably want to start treatment with a different DMARD.  It’s also important to check a complete blood panel and check your liver and kidney levels before starting methotrexate.  This is for the same reasons as the chest x-ray, safety.

Now once you are on methotrexate, it’s important to watch for side effects.  Typically, you need bloods every 3-4 weeks in the beginning and then every 3 months once you are on a stable dose.  This is important because you may not necessarily physically feel you are becoming more anemic or that your liver is inflamed.

On a side note, if you check the bill you received from your insurance company, you might see the code “high risk medication monitoring – Z79.899”.  This does NOT mean you are participating in questionable or “high risk activities”, if you know what I mean.  It simply means that your doctor needs to check your labs on a frequent basis because of the medications you are taking.

4. What about combining other medications with methotrexate?  Is it safe?

Methotrexate is commonly combined with other medications.  About 1/3 of people treated with methotrexate for rheumatoid arthritis will either have very little symptoms or will go into remission.  The other 2/3 will need to use combination therapy.  Methotrexate is commonly called the “anchor” in rheumatoid arthritis treatment regimens.  Some medications are safe to combine and some are not.  This will depend on many factors like lifestyle choices, your other different medications, liver status, and your other medical conditions.

5. How much alcohol is safe for me to drink with methotrexate?

Methotrexate can potentially cause inflammation of the liver.  So technically, it’s probably not a good idea to drink any alcohol while taking methotrexate.  That being said, drinking one standard glass of alcohol once a week probably is safe.  This is a bit of a touchy subject, and you should discuss this more with your doctor.  If you click the following link, I have a full article dedicated to this topic.

These are the NIH's standard alcohol units

By National Institutes of Health [Public domain], via Wikimedia Commons

6. Do I have to worry about infections with methotrexate?

Whether methotrexate significantly increases your risk of infections is poorly understood and there is a lot of conflicting data out there.  Most serious infections tend to occur in people receiving both methotrexate and prednisone or with another biologic agent at the same time.  To be extra cautious I would say, low dose methotrexate (i.e., max 25 mg once weekly) could predispose you to have more infections but the risk is probably very small.  In fact, recent data even suggests that continuing methotrexate during the time around orthopedic surgeries is probably fine.  More data is needed though.  That being said, it’s important to be up-to-date with vaccines and to regularly wash your hands especially during flu season.

7. What do I do if I’m planning to become pregnant?

Methotrexate can cause miscarriages and can cause fetal abnormalities.

You absolutely, cannot be on this medication during pregnancy.

It sticks around your body for a long time.  If you plan to become pregnant, you need to come off the medication 3 months before trying to conceive.  Before making any changes, please discuss with your rheumatologist.  Open communication is key!

8. What does my husband do if we want to have children and he is on methotrexate?

Same as the above.  The rules for men are the same for women.

9. Is breast-feeding safe while taking methotrexate?

No.

10. Does methotrexate cause cancer?

To answer this question, I need to discuss methotrexate dosage.  In rheumatology, we use low doses of methotrexate (i.e., max 25 mg once a week).  When using methotrexate for cancer, we’re talking a dose of at least 500 mg/m².  The doses vary from cancer to cancer but we’re talking massively larger doses than for rheumatoid arthritis.  Increased risk of malignancy caused by methotrexate has been described in people with concurrent Epstein Barr infection and lymphoma as well as MALT (mucosa-associated lymphoid tissue) lymphomas.  Moreover, MALT lymphomas tend to regress when you stop methotrexate.  There actually isn’t any good quality data supporting the theory that low dose methotrexate directly causes solid cancer, skin cancers, or leukemias.

This isn’t to say that you will not develop cancer while taking low dose methotrexate.  It’s just that it probably wasn’t the methotrexate that caused the cancer.

It all boils down to benefit versus risk.  What is the risk of not treating rheumatoid arthritis?  What is the risk of developing a serious side effect from methotrexate?  Does methotrexate have a good chance of halting the progression of rheumatoid arthritis?  The answer to these questions is different for everyone.

What I would say is that the potential benefits of methotrexate more often than not, vastly outweigh the risks.  Again, this is an important discussion you should have with your doctor.

References

Weinblatt ME. Methotrexate in rheumatoid arthritis: a quarter century of development. Trans Am Clin Climatol Assoc. 2013;124:16-25.

Rheumatology Secrets, 3rd edition

Saitoh M, Matsushita K. Prevention of surgical site infection for orthopedic surgery in rheumatoid arthritis. Nihon Rinsho. 2016 Jun;74(6):993-9.

Malaviya AN. Low-dose methotrexate (LD-MTX) in Rheumatology Practice – A widely misunderstood drug. Curr Rheumatol Rev. 2016;12(3):168-176.

Hellgren K, et al. Rheumatoid arthritis and risk of malignant lymphoma- Is the risk still increased? Arthritis Rheumatol. 2016 Dec 19. doi: 10.1002/art.40017.

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