Recent Research on Insulin Resistance and Rheumatoid Arthritis

About two years ago I wrote a three part series on the increased risk of cardiovascular disease (CVD), diabetes, and metabolic issues for people with rheumatoid arthritis. The articles are listed below.

• Metabolic Syndrome Part 1
• Metabolic Syndrome Part 2
• Metabolic Syndrome Part 3

Metabolic syndrome involves a set of interconnected risk factors that are related to cardiovascular disease and diabetes (see this excellent overview from the U.S. National Institutes of Health). All of these complex biochemical processes are connected and involve metabolism of food for energy, sugar processing, insulin, insulin resistance, fat/lipids including cholesterols and triglycerides, liver health, food types, excess weight, exercise, and systemic inflammatory responses. Whenever one of the interconnected systems gets out of normal parameters, a cascade of problems may occur which may impact cardiovascular health. In a study published in 2013, it was found that 18-49% of RA patients also had metabolic syndrome that was significantly higher than general populations. These researchers also found that RA patients with higher inflammatory blood markers and those who used corticosteroids were more likely to show signs of metabolic syndrome. Anti-inflammatory treatments for RA including DMARDS and many of the biologicals like anti-TNFs may impact the biochemical pathways involved in metabolism (see this recent study). Cardiovascular risk is one extra-articular manifestation of RA that can have serious and fatal consequences.

According to the U.S. National Institutes of Health,

“Insulin resistance is a condition in which the body produces insulin but does not use it effectively. When people have insulin resistance, glucose builds up in the blood instead of being absorbed by the cells, leading to type 2 diabetes or prediabetes.”

A review of research conducted by European rheumatologic researchers (Amaro, et al., 2011) connected insulin resistance to RA. They revealed that insulin resistance was more common in RA patients with higher inflammatory blood markers (c-reactive protein, ESR) and disease activity measured by the DAS28.

A recent study published in the journal Arthritis and Rheumatology focused on insulin resistance and RA. Giles, et al., 2015 stated that the connection between insulin resistance and RA is poorly understood. They examined almost 400 people, 200 RA patients and 200 non-RA patients. They measured variables associated with CVD and insulin resistance. They found that insulin resistance levels were much higher in the RA group and demographic factors did not play a role. Insulin resistance was higher in patients with positive rheumatoid factor (RF) tests for both genders and higher for women who use steroids. They concluded by arguing that while insulin resistance levels were higher in RA patients, it remains unclear how this impacts cardiovascular risks.

More research is needed into this critical area of extra-articular (outside the joint) affect of rheumatoid arthritis.

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Kinase Inhibitors in the Development Pipeline for RA

In an earlier post, I documented some of the new biologic medicines for RA in the development pipeline. There continues to be a constant stream of biologic drugs in research and development. But in the past few years, a new line of research led to the investigation of a set of molecules called kinases that are involved in the complex biological processes of RA. The development of kinase inhibitors is based on the theory that inhibition can slow down the production of inflammatory cytokines thereby controlling the disease processes. These processes are linked to the so-called JAK-STAT pathway that is being studied in numerous diseases.

Currently, there is only one kinase inhibitor approved for RA in the United States. Xeljanz, or tofacitinib, was developed and is marketed by Pfizer. The European Medicines Agency did not approve Xeljanz because of lack of efficacy and safety. Some European and Arab countries including Russia approved it.

Below is a list of some of the Kinase inhibitors currently in the development and trial pipeline. There are many others that died in the development pipeline.

Baricitinib by Eli Lilly and Incyte Corporation. Currently in Phase III clinical trials.

Fostamatinib by Rigel. In Phase II clinical trials. Efficacy is questioned.

CC-292 by Cellgene. In Phase II clinical trials.

PLX5622 by Plexxikon. In Phase I clinical trials.

AB494 by Abbvie. In Phase II clinical trials.

HM71224 by Hanmi. In Phase I clinical trials.

It remains to be seen whether or not JAK-STAT inhibitors will become a fruitful treatment option for those with rheumatoid arthritis.

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Using Evidence-Based Medicine to Make Decisions About Treating Our RA

Given the overwhelming glut of information, patients need to be armed with knowledge in order to be good patients and consumers. This is where evidence-based medicine comes into play. Evidence-based medicine is used as the foundation for the current training and practice of medical doctors, physical therapists, pharmacists, and nurses. It is the norm in the Western world. According to Sackett, et al (1996),

“Evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external clinical evidence from systemic research.”

There are multiple sources of evidence ranging from opinions of authorities to the ultimate source of evidence – the randomized control trial (RCT). The RCT is the “gold standard” of medical research. In a RCT, patients are randomly assigned to either receive a treatment or placebo. Government regulations require the extensive use of these designs for the approval of medical treatments. For drug approval, years of development and testing are required from testing on animals through three phases of clinical trials on humans…

read the entire article at http://rheumatoidarthritis.net/living/using-evidence-based-medicine-make-decisions-treating-ra/

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Platelet-Rich Plasma Injections: A Viable Treatment for RA Joint Damage?

My right elbow has been giving me troubles for over a year now and my rheumatologist referred me to an orthopedic surgeon who specializes in hands and elbows. An MRI revealed a 50% tear in a tendon. Other parts of the elbow exhibit pain. In fact, the left elbow also displays the same symptoms but to a lesser extent probably due to the fact that I am right handed. The orthopedic doctor knows about my struggles with RA and my history with soft tissue damage. In fact, he works in the same clinic with the surgeon who conducted three surgeries on my ankles.

A bevy of conservative treatments were prescribed starting with rest and immobilization with splints designed to prevent movement of the tendon. After that failed to help, a cortisone injection was done. The doctor also used the needle to aggravate the tissue in the joint in order to stimulate a healing process by increasing blood flow to the region. Needless to say, excruciating pain was experienced for the next 24 hours but after that, the steroid provided some relief…for about 1 month after which time the pain returned. Occupational therapy was then prescribed. Occupational therapists (OT) tend to focus on the arm from the elbow down to the hand and they engage in treatments similar to physical therapists. Treatments included heat and transcutaneous electrical nerve stimulation (TENS), gentle stretching exercises, and continued use of immobilization with splints. The goal was to move into more rigorous strength building exercises. But this goal was never met as the pain only became worse. After several months of OT, the therapist made the decision that things were getting worse and indicated that I need to return to the surgeon to determine next steps. At about this time, severe neck problems were popping up and the orthopedic surgeon and I both agreed that priority needed to be given to the neck. The past six months were devoted to recovering from neck surgery.

The elbow continued to cause problems and it came to the point where use was difficult and pain was constant so I returned to the orthopedic surgeon. He said that surgery to repair the torn tendon and its attachment point to the bone would be the next option. But before doing that, he wanted to try one more, last ditch strategy – a platelet-rich plasma injection or PRP. He admitted that the research was sketchy and that it was not an FDA or insurance approved treatment. I would be required to pay for it out of pocket and the cost will be about $300. His argument is that in spite of the lack of experimental research on its effectiveness, there is clinic evidence, it is relatively inexpensive, and it is not as invasive as surgery. He did give me a choice between PRP and surgery but his comments were, “If it were me, I would do this first before having surgery.”

In PRP, a patient’s blood is drawn, platelets are separated from other blood components, and the concentrated solution is injected into a joint that has tissue damage in an effort to jump-start a healing process.[1] The theory is that growth factors contained in the platelets are able to help damaged tissue heal. It has been applied to tendon areas like the Achilles and elbow where there is a lack of blood low and healing is difficult. This approach is quite popular with professional athletes but clinical trails show mixed results (Harmon & Rao, 2013).[2]

In medical practice, there is a range of possible qualities of treatments. Balshem et al (2010) categorizes the ranges from very low quality to high quality evidence.[3] The approval of drugs would rate as high quality evidence. At the lowest end of the evidence quality continuum would be treatments that have little or conflicting evidence. Platelet-rich plasma would rank at the lowest end. This is why the FDA and insurance companies won’t approve it. There is even less research about PRP and rheumatoid arthritis. A search of research studies specific to RA revealed one study conducted on pigs[4] and another conducted in 1989 on knees of RA patients.[5] Never provided sufficient evidence documenting the effectiveness of PRP for rheumatoid arthritis.

Given the lack of evidence, I remain quite skeptical about PRP but am willing to give it a shot (pun intended) in order to avoid surgery.

[1] http://orthoinfo.aaos.org/topic.cfm?topic=A00648

[2] http://www.ncbi.nlm.nih.gov/pubmed/24319241

[3] http://www.jclinepi.com/article/S0895-4356(10)00332-X/abstract

[4] http://onlinelibrary.wiley.com/doi/10.1002/art.30547/full

[5] http://link.springer.com/article/10.1007/BF00270285#page-1

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The American Autoimmune and Related Diseases Association (AARDA)

Rheumatoid arthritis is one of many autoimmune diseases (AD). In a normal immune response, white blood cells identify foreign invaders like bacteria and viruses. They produce antibodies against these invaders so other cells can destroy them. In an autoimmune response, your white blood cells have difficulty distinguishing between foreign invaders and your own healthy cells – in essence, your body attacks itself.¹

It is estimated that upwards of 22 million Americans suffer with an autoimmune disease and more than 80 ADs have been identified.² Some of the most common autoimmune diseases include rheumatoid arthritis, type I diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel diseases, and psoriasis.³ The financial impact of these diseases is in the billions. Autoimmunity tends to more common in women and the ratio of women to men with RA is about 2.5 to 1.⁴ It is common for people to suffer with multiple autoimmune diseases.

Given the dramatic impact of autoimmune diseases on society and the interrelatedness of autoimmune diseases,⁵ it is important that awareness efforts be pursued. The American Autoimmune and Related Diseases Association, or AARDA, is the only non-profit organization devoted solely to raising awareness of autoimmune diseases.

Read the rest at http://rheumatoidarthritis.net/living/american-autoimmune-related-diseases-association-aarda/

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Why Can’t RA and Autoimmune Diseases Get the Same Attention as the ALS Ice Bucket Challenge?

The Ice Bucket Challenge for ALS is all the rage right now. Hardly a day goes by that I don’t see a post on my personal Facebook page with someone pouring ice over his or her head and daring someone else to do it. It seems that every celebrity is getting on board ranging from Bill Gates to Lady Gaga. To date, over $22 million has been raised by this strategy.[1] This got me thinking about why RA and related autoimmune diseases can’t get this sort of public attention.

Amyotrophic lateral sclerosis (ALS) is also known as Lou Gehrig’s Disease after the famous baseball player. According to the ALS Association, 5,600 people are diagnosed with ALS each year in the United States and it is estimated that 30,000 some people currently live with the disease.[2] It is true that half of all people diagnosed with ALS will die within a few years and it is a most devastating disease.

However, the impact of RA on Americans is vast compared to many other diseases. Over 1.5 million Americans suffer from rheumatoid arthritis and upwards of 23 million suffer from an autoimmune disease.[3] Arthritis is the leading cause of disability and work limitations in the United States. The financial impact on the workplace and personal lives of those affected is close to 100 billion dollars annually. There are over 10,000 arthritis related deaths every year. [4] The direct healthcare costs of autoimmune diseases are estimated at $100 billion annually compared to $57 billion annual for cancer.[5] Autoimmune diseases receive much less research funding annually than cancer – about $800 million dollars in research funding every year compared to all cancers funding at $7 billion.[6]

There are many diseases worthy of public attention and research funding. And ALS is certainly one of those. But I am frustrated by the lack of public attention and funding for autoimmune diseases in general and RA specifically. Can’t someone come up with a promotion for RA that will grab the public’s attention?

[1] http://www.alsa.org/news/media/press-releases/ice-bucket-challenge-081914.html

[2] http://www.alsa.org/about-als/who-gets-als.html

[3] http://www.aarda.org/autoimmune-information/autoimmune-statistics/

[4] http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm

[5] http://www.aarda.org/autoimmune-information/autoimmune-statistics/

[6] https://livingwithra.wordpress.com/2013/01/31/research-funding-priorities-for-rheumatoid-arthritis/

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RA Fatigue is Complex, Poorly Understood, and not Treated

Hardly a day goes by on the rheumatoid arthritis Facebook site that a person doesn’t mention their persistent battle with fatigue. It’s one of the most frustrating symptoms of RA and there’s no treatment that directly affects it.

Fatigue is a common problem seen is almost all autoimmune diseases.[1] Your body feels completely wiped out, energy levels are low, it’s hard to move, and your cognitive function is poor.

Read the rest of the article at http://rheumatoidarthritis.net/living/ra-fatigue-complex-poorly-understood/

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