Anti-Inflammatory Drugs for Multiple Sclerosis

Multiple sclerosis is a disease that affects the brain and spinal cord. It involves an immune-mediated process, which results in an abnormal response. Such abnormal response leads to the damage of the central nervous system tissue and the immune system, which attacks the myelin causing demyelination.

Risk Factors

Genetic factors do not seem to play a role, but if there has been a family history of multiple sclerosis, then the chances are slightly higher.

People in northern latitudes were believed to have greater chances of developing this disease. However, this scene has changed in the past 30 years and more cases are now being diagnosed in temperate regions such as Latin America.

Symptoms

The following are the symptoms of multiple sclerosis:

• Dizziness
• Double vision
• Numbness and tingling sensations
• Visual changes
• Weakness
• Vertigo
• Balance problems when walking
• Lack of coordination of the arms or legs
• Slurred speech
• Incontinence or inability to empty the bladder

Some may develop muscle spasticity or involuntary painful muscle contraction as the condition progresses.

Types

• Relapsing-remitting multiple sclerosis - It is the most common type of multiple sclerosis. Symptoms developed by some people may resolve with the help of treatment. Remission episodes can last for weeks or sometimes for years.

• Secondary progressive multiple sclerosis - This type of MS occurs when the exacerbation does not completely resolve during a remission.

• Primary progressive multiple sclerosis - In this type of multiple sclerosis, the disease progresses without relapses or remission. There is also no improvement in the symptoms.

• Progressive-relapsing multiple sclerosis - This type of MS is identified when over a period of time, the person experiences escalating symptoms as well as intermittent episodes of the symptoms.

Multiple sclerosis is a disease that causes inflammation and damage to the brain and spinal cord. This further gives rise to symptoms such as trouble walking, muscle spasticity, impaired vision, and numbness. The inflammation occurs at the myelin sheath, which is around the nerve coating. The nerve fibers are unable to function properly. Dissipation of the inflammation will enable the myelin sheath to heal and repair itself, so the nerves will properly work again. However, if the inflammation is constant or repetitive, then it can leave a scar, which can further lead to permanent nerve damage. Most people with multiple sclerosis have multiple areas of scarring, hence, the name of the disease.

Interferon Beta-1a

Interferon beta is an immunomodulator medication. It is used for the treatment of relapsing multiple sclerosis. This medication is recommended for an active multiple sclerosis treatment. Interferon beta can be taken with the following conditions:

• If the person has a relapsing multiple sclerosis and has a recent relapse
• If the MRI scan indicates that the MS is active
• If the person has secondary progressive multiple sclerosis and has relapses
• If the person has CIS or clinically isolated syndrome and the chances of getting MS is indicated in the brain scan

Function

Our body makes its own protein called interferon. Beta interferons are man-made versions, which help reduce the inflammation and nerve damage in patients with MS. Beta interferons are given in the form of injections with a "pen", which means that the needle penetrating into your skin is not visible.

These drugs can be grouped based on how well they control inflammation as well as how well they reduce relapses and slow down the disability from getting worse. Beta interferons are classed as "moderate" drugs. In trials, on an average, it was found that there was a 33 percent drop in relapses. This trial was compared to those people who took a placebo. By making use of a modest amount, it was found that a worsening disability could be slowed down.

Side Effects

There are certain side effects associated with beta interferons. Some people may experience flu, headaches, muscle ache, chills, or fever, which usually last for two days after the injection. Often, these symptoms get better. Ibuprofen or paracetomol can be taken for relief of these symptoms.

There can be redness, bruising, or itchiness at the injection site. In some patients, the drug may cause depression. Thus, this drug is not recommended for people who have had depression in the past.

Usage

Interferon beta-1a comes as a powder in vials. It needs to be mixed first with a solution before injection. It also comes as prefilled injection syringes and in a prefilled automatic injection pen. It is injected once a week. Follow the prescription label carefully and use the medicine as directed. The first dose is given by the doctor. After that, you can inject it or ask your family members to do it for you.

Common Brands

• Avonex - In Europe, this drug was approved in the year 1997 and 1996 in the US. Since then, it is registered in many other countries. This medicine is available as a prefilled syringe or automatic injecting pen, which is injected into the muscle. If it comes in the form a powder, then it should be mixed first before injecting. The dose is once a week. The premixed version should be kept in the fridge. A week before its use, this medicine should be stored at room temperature. It was produced by Biogen, a biotechnology company.

• Plegridy - It is another trade name of interferon beta-1a. It is injected under the skin. It also comes as a prefilled syringe or automatic injecting pen. Its advantage is that it can be taken once in every two weeks. It should be kept out of sunlight. You can store it in a refrigerator, but do not freeze it. Before injecting, it should be brought to room temperature.

• CinnoVex - This is manufactured as a biosimilar or biogeneric drug in Iran. It is produced in a lyophilized form. It is sold along with distilled water for injection. This drug was developed by Fraunhofer Institute in collaboration with CinnaGen.

• Rebif - This drug is used for the treatment of multiple sclerosis in isolated syndromes as well as relapsing forms. It works quite similar to that of interferon beta protein, which is produced by humans. In the US, this medicine is marketed as Merck Serono. It was approved in the year 1998 in Europe and 2002 in the US. Since then, it was approved in many countries. It is injected under the skin. It is available in the form of a prefilled syringe or an automatic injecting pen. It is also available as an electronic injection device called RebiSmart. Rebif has to be given three times a week. For two weeks, it can be stored at room temperature or it can be stored in the refrigerator.

Reviews

The reason behind the use of interferon beta for the treatment of multiple sclerosis is linked to its antiviral and complex immunoregulatory activities. Avonex (interferon beta 1-a) is derived from human fibroblasts and is indistinguishable from the natural interferon. Its effects have been implicated in the pathogenesis of multiple sclerosis and have been documented, although its mechanism in treating MS is unknown.

T cell activation and migration into the CNS is the primary process in the pathogenesis of multiple sclerosis. A significant reduction in the expression of T cell surface activation markers was noted when in vitro and in vivo studies were done with interferon beta-1a compared to placebo or no treatment. It also significantly increased the levels of interleukin-10 in CNS, which is a potential inhibitor of cell-mediated immune responses. 

The optimal route of administration of interferon beta-1a is through an intramuscular injection. A significant extension in the onset of sustained neurological disability was noted when trials were conducted in patients with relapsing-remitting multiple sclerosis taking interferon beta-1a once a week for two years by intramuscular injection compared to placebo. This study was supported by MRI data where the lesions also reduced in number and volume.

A retrospective statistical analysis of the disability outcome data that was obtained in the trial showed beneficial effects of the drug. It has been observed that interferon beta-1a slows the disease progression in patients with relapsing multiple sclerosis without any adverse toxicity. Also, the rate or relapse that was measured clinically and through MRI showed a reduction. The use of this drug in the treatment of multiple sclerosis shows a promising advance in drug therapy.

How does it help?

Eukaryotic cells produce interferons and they belong to a family of naturally occurring proteins. Interferons are produced in response to viral infections and other biological inducers. They posses antiproliferative, antiviral, and immunomodulatory biological activities.

Interferons exert a biological effect by binding to specific receptors on the cell surface. Due to binding, a complex cascade of intracellular events is initiated, which causes expression of several interferon-induced gene products and markers. They may mediate some biological activities.

The mechanism of interferon beta-1a in treating multiple sclerosis is not yet completely defined. Interferon beta balances the expression of pro- and anti-inflammatory agents in the brain. Thus, the number of cells that cause inflammation and cross the blood-brain barrier is reduced. However, overall therapy reduces the inflammation of neurons. Interferon beta is known to improve neuronal survival by increasing the production of the nerve growth factor. In vitro studies have found that interferon beta reduces the reproduction of Th 17 cells. These cells are known to play a role in the pathophysiology of MS. These cells are a subset of T lymphocytes.

Why anti-inflammatory?

The main objective of the treatment is to provide relief from the disease and treat acute exacerbations. It shortens the duration and prevents the disease progression by reducing the frequency of relapses. Approved drugs should reduce the frequency of exacerbation and slow the disability from becoming worse.

Such drugs are known as disease-modifying drugs, which can be classified as immunomodulators. In multiple sclerosis, proinflammatory cytokines and interferon gamma are expressed, which are major factors for triggering the autoimmune reaction that leads to MS. Interferon beta-1a inhibits the expression of proinflammatory cytokines and interferon gamma.

Interferon beta-1b inhibits the expression of proinflammatory cytokines including the interleukin-1beta, TGF-beta, IL-6, tumor necrosis factor-alpha, and interferon gamma. They are known to play a major role in triggering an autoimmune reaction.

Side Effects

Common side effects include:

• Chest pain
• Chills
• Cough
• Fever
• Diarrhea
• Headache
• Flu-like symptoms
• Black, tarry stools
• Joint pain
• Muscle aches
• Nausea
• Painful or difficulty urinating
• Shortness of breath
• Swollen glands

Some may experience unusual bleeding or bruising, unusual tiredness or weakness, sores, ulcers or white spots on the lips or mouth.

The less common side effects include:

• Abdominal or stomach pain
• Convulsions
• Difficulty swallowing
• Decreased hearing
• Dizziness
• Fainting
• Warm feeling
• Mood changes
• Muscle spasms
• Hives or itching
• Pain or discharge from the vagina
• Redness of the face, neck, or arms
• Runny nose or stuffy nose
• Skin lesions
• Sore throat
• Swelling of the face, lips, or eyelids
• Troubled breathing
• Pelvic discomfort
• Aching or heaviness
• Redness, swelling, or tenderness at the injection site

Rare symptoms include:

• Earache
• Loss of appetite
• Painful blisters in the trunk of the body
• Painful cold sores
• Blisters on the lips, nose, eyes, or genitals
• A feeling of discomfort or illness

Many people experience initial symptoms that are similar to flu, such as headache, fever, chills, tiredness, and muscle aches. However, these symptoms only last for several days and improve or go away after a couple of months. The symptoms can be reduced at bedtime by taking fever reducers or pain relievers such as acetaminophen or ibuprofen before taking the dose. 

Inform your doctor immediately if you experience any of the following conditions:

• Worsening depression
• Suicidal thoughts or psychosis
• Feeling too hot or cold
• Blue fingers or toes
• Gradual weight change without a change in diet or exercise
• Infection or change in skin color at the site of injection
• Signs of kidney problems
• Signs of liver problems

Get medical help if there are any serious side effects such as seizure.

Interferon beta-1a lowers the ability of the body to fight infections. The person is likely to get some serious case of infection or any existing infection may worsen. Thus, you should inform the doctor if you have any signs and symptoms of infection such as sore throat, fever, chills, or cough. Allergic reactions are rare. Get medical help right away if you experience itching, swelling, rash, severe dizziness, trouble breathing, or any other allergic reactions.