Author: Danielle Bakertcy

27 Mar 2018

Manly MS Resistance?

Multiple sclerosis is often thought of as more of a female disease. This is because women are twice or even three times as likely to develop multiple sclerosis compared to men. This gender difference has led researchers to explore the influence of sex hormones in this disease.

Testosterone – which men typically have in higher amounts than found in women – is thought to play a role in this autoimmune disease of the brain and spinal cord. New research in animal models suggests that the presence of testosterone can lead to a “guardian molecule” patrolling the body. This guardian molecule is an immune compound called cytokine IL-33 that can prevent damage to the myelin sheath. In the animal research, myelin damage was even reversed by the presence of this guardian molecule. This is exciting, since myelin sheath damage leads to the movement problems and cognitive symptoms of multiple sclerosis in humans.

While it is not viable to increase testosterone levels in all women, it is possible to work on ways to activate the guardian molecule. This is an interesting new area of multiple sclerosis research that could bring real benefits in the near future to multiple sclerosis patients.

While a potential new treatment for MS related to understanding testosterone continues to be developed, there are numerous medications for this disease that are already available, including Ocrevus which was discussed this this recent blog: A Look Back at 2017’s FDA Approvals.

Source

Russi AE, el al, Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility. PNAS 2018 http://www.pnas.org/cgi/doi/10.1073/pnas.1710401115

20 Mar 2018

Hepatitis C and Diabetes: A Complicated Relationship

Guest blog by: Erica Yelton, Pharm.D., CSP, Pharmacy Center Manager, BioPlus Specialty Pharmacy

Hepatitis C and diabetes are both prevalent, global diseases with long-term implications in terms of morbidity and mortality. The World Health Organization reports that 170 million people are infected with hepatitis C and 347 million people suffer with diabetes. Most studies show that patients with hepatitis C are more susceptible to developing type 2 diabetes. It is estimated that up to 33% of chronic hepatitis C patients have type 2 diabetes. The connection between these diseases is seen in both developed and developing countries. The central component of developing insulin resistance is the intense inflammatory response to the hepatitis C virus (HCV) which disrupts the insulin signaling pathway. Also, inflammation causes pro-inflammatory cytokines to be released causing damage to beta cells. Beta cells are the producers of insulin in response to glucose. Studies have shown that HCV can directly and indirectly induce beta cell dysfunction.

On the reverse side, patients with type 2 diabetes are at a higher risk for complications from HCV. Patients with HCV and insulin resistance have been shown to have significantly worse outcomes. Some of these include decreased SVR rate, increased progression of fibrosis and cirrhosis, and increased risk of hepatocellular carcinoma. When insulin is increased, which happens in those with insulin resistance, it stimulates hepatic stellate cells which produce nonfunctional matrix and scarring, AKA fibrosis. This occurs in a dose dependent fashion. Insulin resistance also causes increased release of fatty acids from adipose and increased lipid deposition both of which are associated with fibrosis. Patients with diabetes are also at an increased risk for various malignancies including hepatocellular carcinoma. Insulin, insulin-like growth factor, and chronic inflammation have all been implicated in carcinogenesis.

To further complicate the scenario, interferon, which was once the mainstay treatment for HCV, is now known to cause type 1 diabetes! Interferon is a known potent immunomodulator and can contribute to autoimmunity. In most cases studied of patients who developed type 1 diabetes, the onset occurred during or shortly after treatment with interferon. To date, there are greater than 45 known cases. It is important to suspect type 1 diabetes in patients who present with polydipsia and polyuria after treatment with interferon. Since treatment regimens now steer away from interferon, it may be that the rate of type 1 diabetes as a complication of treatment decreases.

On one hand, HCV triggers diabetes and on the other hand, diabetes worsens hepatitis C outcomes. It is recommended to screen for diabetes in all HCV-infected patient regardless of age or medical history and especially important in patients with known autoimmune conditions. The complicated relationship between these two disease states will have to be addressed until hepatitis C is eradicated and even then, the lasting effects of complications will still have to be dealt with.

Source: Hammerstad SS, Grock SF, Lee HJ, et al. Diabetes and hepatitis C: a two-way association. Frontiers Endocrin 2015;14(6):134.

13 Mar 2018

The Prostate Cancer Toolkit

For men, prostate cancer remains the second most common type of cancer. Only skin cancer is more prevalent. Over the course of his lifetime, one in every seven men will develop prostate cancer and one in 39 men will die of prostate cancer. The difference in those numbers means that lots of men are surviving this disease.

There are more medications than ever before available for the treatment of prostate cancer, with a new medication joining the ranks recently. On February 14, 2018 the FDA approved Janssen’s Erleada™ (apalutamide) for the treatment of patients with prostate cancer that has not spread (non-metastatic), but continues to grow despite treatment with hormone therapy (castration-resistant).

This oral medication earned FDA approval months ahead of the scheduled decision date and is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer. The FDA’s fast approval turnaround of Erleada was based on clinical trials of this medication showing a 72% reduction in risk of metastasis or death. There are currently 2.9 million American men who were previously diagnosed with prostate cancer who are still alive; this medication will only be increasing this impressive number.

Prostate Cancer Risk Factors

Age: As your age goes up, so does the risk of prostate cancer.

Race: Prostate cancer is more common in African-American men.

Family history: If you have a close relative with prostate cancer (father, brother, or son), then you are at higher risk.

Obesity: A higher BMI (a measure of body fat) increases the risk of this disease.

Source

Press release. FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint. U.S. Food and Drug Administration February 14, 2018.

PATIENT EDUCATION TOOLKIT:

PSA Test: Reconsidering the Recommendation 
Recommendations for the PSA prostate screening test are being revisited.

3 FREE Posters + 25 BioHeadlines : PSA The Prostrate Cancer Screening Test – Patient Education Handout

06 Mar 2018

Personalizing Crohn’s Disease Treatment

Guest blog by: Marianne Shenouda, Pharm.D., Clinical Pharmacy Specialist, BioPlus Specialty Pharmacy

Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, are chronic inflammatory diseases of the bowel. These diseases can develop as a result of genetic or environmental factors, such as smoking, diet, or any alteration of the normal human gut flora. These factors spur a progressive immune response, which in turn creates mucosal damage to the GI tract.

Symptoms of inflammatory bowel disease run the gamut from diarrhea, abdominal pain, and perianal fistulas to fatigue, weight loss, and/or bowel obstruction. While ulcerative colitis is more closely associated with changes to the inner lining of the colon, Crohn’s disease can affect any segment of the gastrointestinal tract: all the way from mouth to anus.

Treatment for Crohn’s disease focuses on two main types of medications: anti-inflammatory agents and biological treatments. The biological treatments include many medication options: Humira, Remicade, Cimzia, Stelara, Entyvio, and Tysabri. These medications work to alter the immune response of the immune system, by targeting specific proteins that cause inflammation. Humira, for example, targets a protein called TNF-alpha.

Crohn’s disease biological medications can bring great benefits to patients; but unfortunately it is not uncommon for a particular medication to become less effective over time. However, monitoring certain elements of the immune system can guide future treatment. Specifically, monitoring levels of adalimumab antibodies (ATAs) can allow determination if a patient needs a dose increase or if it is appropriate for the patient to switch to another medication within the same drug class. It appears that low trough concentrations may be reflective of a loss of response to Humira (trough levels less than or equal to 5 mcg/ml). In this case, testing for antibodies is suggested. For trough concentrations above 5 mcg/ml, the presence of antibodies are not likely, so the patient may benefit from an increased dose. It was also suggested that adalimumab concentration results above 35 mcg/mL should be drawn at a different time-point other than trough.

Overall ATA testing could lead to a more appropriate and cost-effective management strategy for patients with Crohn’s disease, which is part of an overall move to more personalized treatment of disease.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991576/

https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/64863

27 Feb 2018

Rheumatoid Arthritis: What Should I Eat?

When it comes to rheumatoid arthritis, the foods one eats or avoids can actually affect the symptoms of this autoimmune disease. Dietary interventions can be a useful compliment to pharmacological treatment of rheumatoid arthritis. What it mostly comes down to are certain foods that either promote or discourage inflammation.

Overall, a type of diet known as the “Mediterranean diet” focuses on many of the protective foods while eschewing the problematic foods. Several human studies have documented rheumatoid arthritis symptom improvement, in terms of pain, disease activity, and daily function, when patients transition to a Mediterranean diet.

In addition to the Mediterranean diet, other dietary factors have been either lauded or implicated in rheumatoid arthritis progression and symptoms. Here is a summary of those dietary factors:

Choose These Foods   

Whole grain cereals

Fruits

Oily fish

Plant-based oils (olive oil)

Walnuts

Leafy greens

Legumes

Spices (turmeric, ginger)

Probiotic yogurt

Green tea

 

Avoid These Foods

Meat

Butter

All animal products

Processed foods

Salty foods

Sugar

Saturated fats

 

Sources

Forsyth C, Kouvari M, D’Cunha NM, et al. The effects of the Mediterranean diet on rheumatoid arthritis prevention and treatment: a systematic review of human prospective studies. Rheumatol Int December 18, 2017 doi: 10.1007/s00296-017-3912-1.

Khanna S, Jaiswal KS, Gupta B. Managing rheumatoid arthritis with dietary interventions. Front Nutr 2017;4:52.

20 Feb 2018

Understanding NAFLD and NASH

Guest blog by: Monica Morgan, Pharm.D., CSP

As a specialty pharmacy that works with many patients during treatment for liver diseases, it’s not surprising that questions about nonalcoholic fatty liver disease (NAFLD) come up in our line of work. Although hepatitis C is our primary liver focus, both hepatitis C and NAFLD rank as the two most common causes of chronic liver disease. I’ll be sharing here about why NAFLD deserves some attention and understanding.

What are NAFLD and NASH?

NAFLD is a serious condition in which abnormal amounts of fat build up inside the liver. It’s likely that lifestyle and diet contribute to this process. Nonalcoholic steatohepatitis (NASH) is a type of NAFLD that causes inflammation and liver cell damage, along with fatty build-up in the liver. NASH can progress to scarring of the liver and ultimately to cirrhosis, with all the complications of cirrhosis (e.g., gastrointestinal bleeding, mental changes, liver failure, and liver cancer).

Can we treat NAFLD and NASH?

One of the first things that doctors currently recommend for improving the symptoms and outcomes in NAFLD is to lose weight, as this can reduce fat in the liver, inflammation, and fibrosis. Doctors recommend gradually losing 7 percent (or more) of your body weight over the course of a year or more. This gradual loss is important since rapid weight loss through very low calorie diets or fasting (eating and drinking nothing but water) can actually make NAFLD worse.

No medications have yet been approved to treat NAFLD and NASH; however, there are many therapies in the pipelines that could soon improve the outlook for these patients. Currently, there are varying degrees of success with off-label medications, endoscopic interventions, and bariatric surgery. But researchers are working hard to find other, more reliable treatment options.

There are an estimated 800 clinical trials of potential disease therapies in the works, including trials of the medications cenicriviroc from Allergan, selonsertib from Gilead Sciences, obeticholic acid from Intercept, elafibranor from Genfit, and Emricasan from Conatus Pharmaceuticals. There is hope that within the next couple of years we will have one (or more) FDA-approved treatment options for NAFLD and NASH.

Sources:

https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash

https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/treatment

https://www.medscape.com/viewarticle/872690

https://www.medicinenet.com/fatty_liver/article.htm

13 Feb 2018

Energy Drink Ingredient’s Surprising Role in Multiple Sclerosis

The amino acid taurine has caught the attention of multiple sclerosis researchers. Amino acids are the building blocks of protein. Taurine can be found in many places throughout the body, such as the cardiovascular system where it plays an essential role in heart function, but it also shows up in the central nervous system.

Taurine can be found in many animal-based foods, such as beef, eggs, and dairy products. Interestingly, another place that taurine shows up in significant amounts is in energy drinks, because it is thought to improve athletic performance.

But what about the connection between this amino acid and multiple sclerosis? Researchers at Scripps Research Institute have found evidence that taurine – when combined with multiple sclerosis medications – might make MS drugs work a bit better. The researchers suggest that adding taurine to MS therapy could bring benefits by encouraging remyelination.

In the autoimmune disease of multiple sclerosis, the protective myelin sheath that surrounds nerve cells is attacked by the body’s own immune system. When nerve cells are stripped of myelin, they no longer function properly and symptoms such as numbness, difficulty walking, slurred speech, and vision loss develop. Anything that supports remyelination is beneficial, which is why researchers are so interested in the potential of taurine to make current MS treatments more effective in this regard.

It is particularly promising that taurine is already safely consumed in a variety of ways by humans, so adding it to MS therapy is a low-risk way of hopefully improving outcomes.

Sources

Beyer BA, Fang M, Sadrian B, et al. Metabolomics-based discovery of a metabolite that enhances oligodentrocyte maturation. Nature Chem Bio 2018;14:22-8.

Press release. Taurine lends hand to repair cells damaged in multiple sclerosis. December 7, 2017.

06 Feb 2018

HCV and Children

Hepatitis C screening programs and treatment outreach tend to focus on three key populations: Baby Boomers, IV drug users, and prison populations. This is understandable, since rates of infection are notable in these high-risk groups. However, children infected with the hepatitis C virus (HCV) deserve attention, too. Of the more than 4 million people with HCV in the United States, approximately 250,000 of them are children.

For children, the likely route of infection traces back to mother-to-child transmission from HCV-infected pregnant women. The higher the mother’s viral load, the higher the risk of infection for her child. The infection can be spread whether birth is vaginal or C-section, since the virus from the mother’s body can cross the placenta to the fetus. In fact, up to 10% of children born to mothers with HCV will be infected with this chronic and life-threatening virus. A common scenario is for the mother to be an IV drug user, which can complicate the diagnosis of the child, if the parent does not pursue testing for the child. The screening test for HCV is not accurate until the infant is 18 months old, since HCV-related antibodies from the mother can stay in the blood of an infant for that long, even if the child does not have an infection.

There are fewer HCV medications approved for use in children, compared to the number of medications approved by the FDA for adults. But the positive news here is that there are approved medications for this young population. Hepatitis C does not need to be a death sentence, and certainly not so in children.

Source

Kukielka E. Researchers consider hepatitis C vertical transmission rates. MD MagazineJanuary 14, 2018.

30 Jan 2018

Breast Cancer Treatment Options Expanding

Targeted cancer therapies aim to best match the treatment to specific characteristics of cancer cells. Increasingly, breast cancer treatment is based on targeted therapy medications. With targeted therapy, the harm to healthy cells can be lessened and thus side effects can be less severe than from traditional chemotherapy.

Earlier this month, the FDA approved a new targeted therapy for BRCA-positive, HER2-negative metastatic breast cancer: Lynparza (olaparib). Previously, Lynparza was approved for treating some types of ovarian cancer. Lynparza is a PARP inhibitor. The PARP enzyme’s role is to fix DNA damage, but it does this fixing to both healthy and cancerous cells. By blocking this enzyme, Lynparza helps keep breast cancer cells from growing.

Just about a quarter of patients with hereditary breast cancers and up to one in every ten patients with any type of breast cancer have a BRCA mutation. Women with breast cancer can take a genetic blood test, called the BRACAnalysis CDx, which indicates whether Lynparza would be appropriate targeted cancer therapy for their breast cancer. The results with Lynparza are promising, with a reduction in disease progression or death by 42%, when compared to traditional chemotherapy.

This was not the only good news about breast cancer this month. Kisqali (ribociclib) from Novartis received FDA Breakthrough Therapy designation for initial endocrine-based treatment in premenopausal women with HR+/HER2- advanced breast cancer. Kisqali is a cyclin-dependent kinase 4/6 inhibitor (like the medication Ibrance), which means it works by blocking a certain protein needed in cell division.

The pipeline of new targeted therapies for breast cancer is important news, especially in light of the fact that premenopausal breast cancer remains the leading cause of cancer death in women 20-59 years old.

By The Numbers

12.4%  Women in the U.S. who will be diagnosed with breast cancer at some point in life

266,120  Number of new breast cancer patients estimated in 2018

3.1 million  U.S. women with a history of breast cancer

85%  Women who develop breast cancer despite no family history

Sources

FDA approves first treatment for breast cancer with a certain inherited genetic mutation. FDA News Release January 12, 2018.

Novartis Kisqali® received FDA Breakthrough Therapy designation for initial endocrine-based treatment in premenopausal women with HR+/HER2- advanced breast cancer. Press release January 3, 2018.

23 Jan 2018

The Rheumatoid Arthritis Gender Gap

Rheumatoid arthritis skews very female in the 1.5 million Americans with this disease. There are three women with rheumatoid arthritis to every one man with this autoimmune condition. Furthermore, the disease tends to develop at younger ages in women than in men and also can cause more severe symptoms in women.

While the exact reasons for this gender gap remain unclear, hormones are strongly suspected to play a role. Young women diagnosed with rheumatoid arthritis often wonder if there will be negative effects on their reproductive ability. Interestingly, this condition does go into remission for many (but not all) women during pregnancy, although it almost always returns after having a baby.

The remissions that occur are fortunate, since some rheumatoid arthritis medications cannot be used during pregnancy and breastfeeding, such as methotrexate. However, other rheumatoid arthritis medications do have a record of safe use during at least some of the trimesters of pregnancy, including TNF inhibitors (e.g., Remicade, Enbrel, and Humira), oral steroids, and NSAIDs.

Unfortunately, the latest research about women and rheumatoid arthritis indicates that children born to mothers who have this disease are themselves at a higher risk of developing rheumatoid arthritis. Children with mothers who have rheumatoid arthritis have an increased chance of later developing several conditions:

  • 3 times greater chance of rheumatoid arthritis
  • 2 times higher risk of thyroid disease
  • 6 times increased chance of epilepsy

This latest research highlights the fact that women with rheumatoid arthritis continue to have specific concerns during their reproductive years; some of these concerns can be managed while others need to be monitored.

Sources

Landau MD. Do women with rheumatoid arthritis need to stop medicine while pregnant. Everyday Health December 18, 2017.

Preidt R. If mom has rheumatoid arthritis, baby may develop it, too. HealthDay NewsDecember 11, 2017.