Ocrelizumab (Ocrevus)

Ocrelizumab is a medicine designed to treat multiple sclerosis.  It is indicated for relapsing remitting MS (RRMS) and primary progressive MS (PPMS).  It is made by Genentech.

Ocrelizumab is given by the IV route, 600 mg every 6 months.  The retail cost of the medication is $65000 per year.

Ocrelizumab is an anti CD20 antibody.  It reduces the number of B lymphocytes in the immune system.  It is similar to an older medicine named rituximab.

Clinical trial results

In 480 patients with PPMS treated with ocrelizumab, progression of PPMS was slowed by 24%.   This was assessed over 96 weeks.

For 800 patients with RRMS treated with ocrelizumab, there was a significant reduction in relapses in  over 96 weeks.  Patients treated with ocrelizumab had a 46% reduction in relapses compared to those treated with beta interferon 1a.   About half of the patients had no relapses or new MRI lesions while using ocrelizumab.

Adverse events

Side effects of ocrelizumab are generally reported as mild.  They include infusion site reactions, headache, back pain, fatigue, influenza, upper respiratory tract infection, or depression.

Ocrelizumab should not be used in patients with hepatitis B or other infections.  Ocrelizumab may be associated with a higher rate of new malignancies (cancers) compared to interferon.

 

References:

Hauser SL, et al.  New Eng J Med.  2017  Jan 19   276(3): 221-234

Montalban X, et al.  New Eng J Med.  2017  Jan 19  376(3): 209-220

Infertility management

Women may have problems having a pregnancy for a variety of reasons.  These include:

Body weight far above or below the ideal level

Women who are very thin or very overweight may observe irregularity of their menstrual cycle.  This has an effect on the success of pregnancy, since differences in weight may affect hormone production.  Women who exercise a lot may have similar symptoms.  Some women who are overweight have polycystic ovarian syndrome, a condition that affects egg production and influences body weight.

Changes in hormones that are needed to regulate the monthly cycle

Some women with infertility may have problems making hormones necessary for pregnancy, such as prolactin, FSH or LH.  These hormones can be measured by blood tests, and treatments to replace or influence these hormones levels may be helpful.

Changes in the structures of the fallopian tubes or uterus

A variety of factors can affect the structure of the uterus or the fallopian tubes.  The fallopian tubes are necessary to deliver eggs from the ovary to the uterus, where fertilization and implantation occur.  Fallopian tubes can be affected by conditions like endometriosis or pelvic inflammatory disease.  The uterus can be affected by these causes as well as fibroids, the uterus structure, or other factors.

Treatments for infertility depend on the cause.  Sometimes specialized treatments are helpful for infertility.  These may be stimulation of egg production with a medicine like clomid, in vitro fertilization, or selection of eggs and sperm with normal genetic material to facilitate a healthy pregnancy.

HCG

HCG is a hormone.  It stands for human chorionic gonadotropin.  It’s biological role is to promote the corpus luteum during early phases of pregnancy and to promote the production of progesterone to prepare the uterus for a fetus.

Pregnancy tests detect levels of this hormone.  The level of this hormone is lower at early stages of pregnancy, 5-50 mIU/mL.  These increase with each week of pregnancy, from levels of 1000 to up to 200000.

HCG is similar to LH, a hormone that affects ovulation.  HCG is often used to help women with infertility.  The injection of HCG is used to promote maturation of eggs and ovulation.  Ovulation normally occurs about 36-40 hours after injection.  During IVF procedures, egg retrieval is normally done about 36 hours after HCG, before natural ovulation.

HCG is sometimes used in men to stimulate testosterone production.  It has also been linked to performance enhancement scandals in professional sports.

Gonal F

Gonal F is a hormone medicine.  It is injected under the skin to stimulate egg production.  It is similar to the hormone FSH (follicle stimulating hormone).

Gonal F is often used to treat infertility, in particular for IVF procedures.

Common side effects of Gonal F include abdominal pain, bloating, pain where the injection is given, or a headache.  Serious side effects are rare but they may be trouble breathing, dizziness, bleeding or swelling.

What is Clomid?

Clomid, clomiphene, or serophene, is a medication that interferes with estrogen receptors in the hypothalamus, a hormone regulator in the brain.  The result of clomid treatment is the release of GnRH, or gonadotropin releasing hormone, and resulting increases in FSH and LH release from the pituitary gland.  The causes growth of ovarian follicles, and often clomid is used to stimulate ovulation.

What is infertility?

Infertility is the inability to have a pregnancy within 12 months of trying.  Some of the causes of this condition are related to males, some are related to females.

Common causes of infertility are:

Problems with ovulation / eggs

Problems with the uterus / endometriosis

Blockage of the fallopian tubes

Changes in hormones / prolactin

Male factors / sperm quality

Evaluation of the causes of infertility require a careful evaluation of medicines and medical history, genetic family history, and testing for sperm count, appearance, uterus and fallopian tube anatomy, hormone testing, and sometimes genetic testing of the blood, sperm or the eggs.

How long does the flu shot last?

Answer: forever, but….you should repeat the shot once per year

The flu shot is a mixture of particles from recent common flu viruses from around the world.  This helps the body form an immune response to flu infections- the flu vaccine is known to prevent flu.

There are different formulas for the flu shot.  The formula changes every year, in order to act against the most common viruses.  The flu shot does not protect against all flu viruses- normally just two or three.  Sometimes the vaccine does not cover an unexpected outbreak of a new type of flu virus.  This is why clinical outbreaks occur despite widespread use of the flu shot.

Each year the flu viruses that affect people change, so it is important to have a new flu shot once per year.  The effects of the immune response after one vaccine also decline during the year after treatment.

Is the flu shot ok for MS?

The inactivated flu shot is appropriate and helpful for people who have a history of Multiple Sclerosis. 

There is a potential interaction between interferons (Avonex, Beta Seron, Rebif) and the flu shot.  Both of these can cause flu like symptoms.

The FluMist nasal spray, which contains a live virus, is not recommended.

How long does the flu last?

The seasonal flu is caused by an outbreak of the influenza virus.  This tends to occur during the winter.  The flu normally causes symptoms of fever, muscle pain, fatigue, weakness, and sometimes, coughing, sneezing, or sore throat.  The flu is normally transmitted from person to person via sneezing or coughing.

The time between onset of the illness and exposure is normally 2-4 days.  People with simple flu infections recover in 2-5 days, although durations as long as one week are not uncommon.  In some people, the symptoms may last longer.  These are people who are children or older adults, people with chronic illnesses or immune suppression.

A complicated course of the flu may include associated viral pneumonia, bacterial pneumonia, changes in heart rhythm, confusion and meningitis, or other serious infections.  These conditions are more serious, and they tend to have a longer duration.

Does Prevagen Work?

Prevagen has been touted as a dietary supplement that helps to improve memory.  Does Prevagen work?

Prevagen is a dietary supplement made by Quincy Bioscience, a company based in Wisconsin.  It contains apoaequorin, a protein derived from a jellyfish.  Evidence cited by Quincy Bioscience that Prevagen is effective is reported in a study in 2016.  This study was not published in any journal.

The goal of the study was to determine whether the active ingredient of Prevagen, apoaequorin, improves cognitive function in older adults who have normal or near normal memory function.  In this study, healthy adults ages 40-91 with memory concerns were examined by cognitive tests over a period of 90 days.  People with neurological diseases and other conditions were excluded from the study population.

The authors reported that there were significant improvements in cognitive function in people treated with the study chemical compared to those who were not.

Limitations of this study include:

The study duration was 90 days.

Only participants with minimal or no cognitive impairment were studied.   Results for people with mild or greater memory impairment were not reported.

This study examined a small number of study participants.  Of the 211 people enrolled in the trial, only 100 were included in the final analysis.  Only 37-60 received the test chemical.

With respect to the majority of cognitive tests, the study reports there is a trend to significance.  This is the same as saying there was no change.

They authors state there are significant improvements in the control group compared to the placebo group in three tests.  These are the Groton Maze recall, the Detection test, and the One Card Learning test.  The statistical analysis shows a lack of significant results.  Examining the numbers reported in Tables 3 and 4, there was no significant improvement in either the control group or the placebo group over the time of the study.

The background evidence for the in vitro efficacy of the active ingredient of Prevagen was published.  These include two meeting abstracts and one article in PLoS One.

It would be wonderful if Prevagen improved memory in normal people or people with memory problems.  Although the evidence presented in this study was limited, we are hopeful that better evidence will be reported soon.

Note that The Federal Trade Commission and the State of New York have accused the manufacturer of Prevagen of false advertising.