FREQUENTLY ASKED QUESTIONS

MS is believed to be an autoimmune disease. This means that something triggers the immune system to attack the body. But more specifically, to attack myelin, the protective sheath that covers nerve fibers which interrupts communication between your brain and the rest of the body. The cause of this is unknown. Some doctors think MS may be triggered by an infection, but MS is not contagious. It may also be caused by problems with the immune system.

Relapsing MS includes the following types of MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

CIS is a first episode of neurologic symptoms caused by inflammation and demyelination in the central nervous system.

RRMS—the most common disease course—is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks—also called relapses or exacerbations—are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission. At different points in time, RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity) or not active, as well as worsening (a confirmed increase in disability over a specified period of time following a relapse) or not worsening. Approximately 85% of people with MS are initially diagnosed with RRMS.

A relapse is an event lasting more than 24 hours when old symptoms worsen or new ones appear. Relapses may occur at any time, usually without warning. They can be mild or severe. In relapsing MS, relapses are followed by a long or short period of time when symptoms completely or partially go away.

Over time, MS can lead to permanent brain and spinal cord damage. This damage builds up, eventually leading to increasing levels of disability.

The American Association of Neurology (AAN) says that using a disease-modifying therapy (DMT) can be better than letting MS run its course without treatment. So, you should speak with your healthcare provider to determine if starting treatment is right for you.

Many people on disease-modifying therapies for MS wonder if they’re working, because the results can be hard to see. Whatever you do, don’t stop taking your medicine because you don’t think it’s working or because you don’t think you need it anymore. Talk to your doctor to find out whether the treatment is still right for you.

Choosing the right treatment and staying on therapy can help. Rebif is clinically proven to reduce the frequency of MS relapses. Ask your healthcare provider if Rebif is right for you.

Rebif is a brand name for a product called interferon beta-1a. Interferons belong to a family of proteins that occur naturally in the body. Rebif will not cure MS, but it has been shown to decrease the number of flare-ups and slow the occurrence of some of the physical disability that is common in people with MS. Rebif can cause serious side effects, so before you start taking it, you should talk with your healthcare provider about the possible benefits of Rebif and its possible side effects to decide if it is right for you.

Rebif was approved in 2002 to treat relapsing forms of MS following the completion of 2 studies. One, called the PRISMS^* study, was a placebo-controlled, 2-year clinical evaluation of interferon beta-1a in relapsing MS (RMS). The PRISMS study included 560 people to see how they responded to Rebif 22 mcg or Rebif 44 mcg versus placebo, all given under the skin 3 times a week,^† and was proven effective in treating RMS in 3 ways:

1. Fewer flare-ups
   One of the goals of treatment is to reduce flare-ups. In the 2-year PRISMS study, the 184 people who took Rebif 44 mcg had 32% fewer flare‐ups or relapses than the 187 people on placebo. In other words, on average, people taking Rebif had 1.73 flare‐ups, and people on placebo had 2.56 flare‐ups.
   Rebif, n=184; Placebo, n=187
   P<0.0001
2. Slowed the time to disability progression^‡
   Slowing the amount of time it takes for disability to progress is important. People on Rebif took nearly twice as long to show sustained disability progression. In other words, on average, people taking Rebif took 21.3 months to show sustained disability progression, whereas people taking placebo took 11.9 months.
   Rebif, n=184; Placebo, n=187
   P<0.05
3. Fewer new or enlarging magnetic resonance imaging (MRI) brain lesions^§II
   Lesions are scars that occur in the brain and spinal cord. People taking Rebif 44 mcg in the PRISMS study had fewer new or enlarging brain lesions on an MRI scan. At 9 months, people taking Rebif had 84% fewer Gd-enhancing T1-Gd+ brain lesions compared with placebo. People taking Rebif had a median^¶ of 1.3 Gd-enhancing T1 brain lesions per patient per scan and people taking a placebo had a median^¶ of 8 Gd-enhancing T1 brain lesions^# per patient per scan (Rebif, n=68; Placebo, n= 66; P<0.0001). At 2 years, people taking Rebif had a median^¶ of 0.5 T2 new or enlarging brain lesions per patient per scan and people taking a placebo had a median^¶ of 2.25 T2 new or enlarging brain lesions per patient per scan (Rebif, n=182; Placebo, n=184; P<0.0001).
   

^*Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis.
^†One hundred eighty-nine people took Rebif 22 mcg, 184 people took Rebif 44 mcg, and 187 took a placebo.
^‡Progression of disability was defined as an increase of at least 1 point in the EDSS that was sustained for at least 3 months.
^§Refers to new lesions and total lesion burden or area as defined in the AAN and MS Council guidelines.
^||Lesions detected with both T1-weighted gadolinium-enhanced (T1-Gd+) and PD/T2-weighted MRI.¶A value in an ordered set that has an equal number of values higher and lower.
^#From a subgroup of 134 patients in the PRISMS study who received 11 consecutive monthly PD/T2 and T1-Gd+ MRI scans beginning 1 month before treatment initiation.

Rebif is a self-injected relapsing MS (RMS) therapy proven effective in treating RMS in 3 ways:

• Slowed disability progression
• Reduced relapse rate
• Reduced the number of new or enlarging brain lesions on the studied MRI
  measures^*†

^*Refers to new lesions and total lesion burden or area as defined in the AAN and MS Council guidelines.
^†Lesions detected with both T1-weighted gadolinium-enhanced and PD/T2-weighted MRI.

Important Safety Information

Rebif can cause serious side effects. Tell your healthcare provider right away if you have any of the following while taking Rebif: Behavioral health problems including depression and suicidal thoughts, liver problems or worsening of liver problems including liver failure, serious allergic and skin reactions, injection site problems, blood problems, or seizures.

Rebif is a self-injected relapsing MS treatment proven to work better than another interferon.

The EVIDENCE^* study was a head-to-head trial that compared Rebif with Avonex^® (interferon beta-1a). Rebif 44 mcg was given to 339 people 3 times a week under the skin. Avonex 30 mcg was given to 338 people once a week into the muscle. Results were measured at 24, 48, and over an average of 64 weeks.

Over an average of 64 weeks in a study with more than 600 people, high-dose, high-frequency Rebif 44 mcg was proven superior to low-dose, low-frequency Avonex 30 mcg. When measured at 24 and 64 weeks, more people taking Rebif 44 mcg versus Avonex 30 mcg:

• Were relapse free (percentage of people remained free from flare-ups at 24 weeks of treatment: Rebif, 75%; Avonex, 63%; Rebif, n=339; Avonex, n=338; P<0.001
• Showed fewer new or enlarging brain lesions^† on MRI:
  • More people on Rebif were free of T1‐weighted gadolinium^‡‐enhanced lesions than people on Avonex (at 24 weeks of treatment: Rebif, 58%; Avonex, 38%; Rebif, n=325; Avonex, n=325; P<0.001)

^‡ Gadolinium is a contrast medium injected prior to MRI scans. It passes through breaches in the blood-brain barrier and is therefore used to highlight new and active lesions. The usage of gadolinium greatly enhances the sensitivity of a T1-weighted MRI.

• More people on Rebif showed no new or enlarging T2 brain lesions than people on Avonex (at 24 weeks of treatment: Rebif, 60%; Avonex, 43%; (Rebif, n=325; Avonex, n=325)

Compared with Avonex, side effects were generally similar, with the following exceptions: People taking Avonex had more flu-like symptoms than those taking Rebif. People taking Rebif had a greater number of injection-site reactions, elevated liver enzymes, and decreased white blood cell counts.

At the end of the head-to-head (comparative) phase of the EVIDENCE study, the 605 remaining people were asked if they wanted to leave the study or keep going in the “extension phase.” In this phase, everyone would receive Rebif 44 mcg 3 times a week. Four hundred ninety-five people chose to participate in this phase of the study, which lasted an average of 8 months—73% of those taking Avonex 30 mcg chose to take Rebif 44 mcg—whereas 91% of those taking Rebif 44 mcg decided to stay with it.

Those who chose to stay in the Extension phase and changed from Avonex to Rebif experienced 50% reduction in relapses^†II compared with their last 6 months on Avonex.

^§P<0.001
Rebif, n=223

People who stayed on Rebif had a 26% further reduction in relapses after an average of 8 months. By the end of the head-to-head phase, these people had 0.46 relapses/flare-ups, and in the Extension phase, they had 0.34 relapses/flare-ups (annualized mean flare-up rate)<sup>.‡

§</sup>P=0.028
Rebif, n=272

Rebif can cause serious side effects. Tell your healthcare provider right away if you have any of the symptoms listed below while taking Rebif.

• Behavioral health problems, including depression and suicidal thoughts. You may have mood problems including depression (feeling hopeless or feeling bad about yourself), and thoughts of hurting yourself or suicide.
• Liver problems or worsening of liver problems, including liver failure. Symptoms may include nausea, loss of appetite, tiredness, dark colored urine and pale stools, yellowing of your skin or the white part of your eye, bleeding more easily than normal, confusion, and sleepiness. During your treatment with Rebif you will need to see your healthcare provider regularly and have regular blood tests to check for side effects
• Serious allergic and skin reactions. Symptoms may include itching, swelling of your face, eyes, lips, tongue or throat, trouble breathing, anxiousness, feeling faint, skin rash, hives, sores in your mouth, or skin blisters and peels
• Injection site problems. Symptoms at the injection site may include redness, pain, swelling, color changes (blue or black), and drainage of fluid
• Blood problems. Rebif can affect your bone marrow and cause low red and white blood cell and platelet counts. In some people, these blood cell counts may fall to dangerously low levels. If your blood cell counts become very low, you can get infections and problems with bleeding and bruising. Your healthcare provider may ask you to have regular blood tests to check for blood problems
• Seizures. Some people have had seizures while taking Rebif

The most common side effects of Rebif include:

• flu-like symptoms. You may have flu-like symptoms when you first start taking Rebif. You may be able to manage these flu-like symptoms by taking over-the-counter pain and fever reducers. For many people, these symptoms lessen or go away over time. Symptoms may include muscle aches, fever, tiredness, and chills
• stomach pain
• change in liver blood tests

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Rebif. For more information, ask your healthcare provider or pharmacist.

Do not take REBIF if you:

• are allergic to interferon beta, human albumin, or any of the ingredients in Rebif. See the end of the Medication Guide for a complete list of ingredients in Rebif.

Before you take REBIF, tell your healthcare provider if have or have had any of the following conditions:

• mental illness, including depression and suicidal behavior
• liver problems
• bleeding problems or blood clots
• low blood cell counts
• seizures (epilepsy)
• thyroid problems
• you drink alcohol
• you are pregnant or plan to become pregnant. (It is not known if Rebif will harm your unborn baby. Tell your healthcare provider if you become pregnant during your treatment with Rebif.)
• you are breastfeeding or plan to breastfeed. (It is not known if Rebif passes into your breast milk. You and your healthcare provider should decide if you will use Rebif or breastfeed. You should not do both.)

Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Rebif and other medicines may affect each other causing side effects.

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Rebif is injected under the skin (subcutaneous injection) 3 times weekly, 48 hours apart. There are 3 choices for how to inject Rebif.

Rebif^® Rebidose^® (interferon beta-1a) gives you the option of a preassembled, prefilled, single-use autoinjector.

The Rebiject II^® autoinjector works with the Rebif prefilled syringe and gives you the ability to adjust how deeply the needle will go under your skin.

Rebif is available in preassembled, prefilled syringes. They already contain medicine and do not require needle assembly, so you don't have to worry about mixing any solutions before injection.

You should self-inject Rebif only after you have received proper training from a medical professional. An MS LifeLines^® field nurse may be able to provide injection training for you in the comfort of your home. Call 1-877-447-3243 to learn more.

Rebif can cause serious side effects. Tell your healthcare provider right away if you have injection site problems. Symptoms at the injection site may include redness, pain, swelling, color changes (blue or black), and drainage of fluid. Some patients have developed skin infections or areas of severe skin damage (necrosis) requiring treatment. For more information, please see Medication Guide.

Rebif injections should be taken 3 times a week. Injections should be taken at the same time of day, at least 48 hours apart. Many people choose to take their injections on Monday, Wednesday, and Friday so that they have injection-free weekends. After you decide which 3 days work best for you, stay with those to help make your injections part of your weekly routine.

There are three different injection options: The Rebif^® Rebidose^® (interferon beta-1a) autoinjector, the prefilled syringe alone, or the prefilled syringe with Rebiject II^®. You can decide with your healthcare provider which injection option is right for you. The Rebif Rebidose autoinjector is supplied in packs of 12. Prefilled syringes are also provided in packs of 12. Every effort has been made to ensure that the Rebiject II autoinjectors for use with prefilled syringes will function correctly for at least 2 years. After 2 years of operation, your Rebiject II should be replaced. A new Rebiject II can be obtained by calling MS LifeLines^®, toll-free, at 1-877-447-3243. Your healthcare provider will explain what your starting dose should be and how to increase to your recommended dose.

Rebif Rebidose is a preassembled, single-use autoinjector for taking Rebif.

• No assembly required
• Portable, goes where you go
• Covered needle before and after the injection
• Flexible dosing options (44 mcg and 22 mcg)

Learn more about Rebif Rebidose

Rebif should be stored refrigerated between 36°F and 46°F (2°C and 8°C). Do not freeze. If a refrigerator is not available, Rebif may be stored between 36°F and 77°F (2°C and 25°C) for up to 30 days and away from heat and light. At the beginning of Rebif treatment, your healthcare provider may prescribe a titration phase to gradually increase to the intended dosage.

You should only use Rebif Rebidose after you have received proper training from a medical professional. An MS LifeLines Nurse may be able to provide injection training for you in the comfort of your home. Call 1-877-447-3243 to learn more.

Rebif can cause serious side effects. Tell your healthcare provider right away if you have injection site problems. Symptoms at the injection site may include redness, pain, swelling, color changes (blue or black), and drainage of fluid. Some patients have developed skin infections or areas of severe skin damage (necrosis) requiring treatment. For more information, please see Medication Guide.

Learn more or watch an injection training video

Your healthcare provider may teach you and/or your care partner the proper way to inject Rebif. In many areas, you can also arrange to have an MS LifeLines Nurse visit your home, at no charge, to provide injection training for Rebif. Just call MS LifeLines^®, toll-free, at 1-877-447-3243 Monday through Friday, 8 AM to 8 PM ET, and Saturday, from 9 AM to 5 PM ET.

Do not give yourself an injection until you are comfortable with the dosing and injection process.

Do not heat or microwave the medication. You can allow Rebif to gradually reach room temperature before use (typically 1 to 4 hours before the injection). Doing this may help minimize injection-site discomfort.

Remember to temporarily store your Rebif somewhere safe and out of the way, like a kitchen cabinet. Keep away from heat and light. Room temperature should be under 77°F (25°C) and above 36°F (2°C).

If you miss an injection, you should take your next injection as soon as you remember or are able to take it, then skip the following day. Do not take Rebif on 2 consecutive days. If you accidentally take more than your prescribed dose, or take it on 2 consecutive days, call your healthcare provider right away.

If you accidentally take the wrong dose, call your healthcare provider right away.

Store Rebif in the refrigerator between 36°F and 46°F (2°C and 8°C). If a refrigerator is not available, it may be stored between 36°F and 77°F (2°C and 25°C) for up to 30 days, away from heat and light. Do not freeze Rebif or inject Rebif that you suspect has been frozen.

There are special state or local laws for properly disposing of used needles, syringes, and Rebif Rebidose autoinjectors. Your doctor or healthcare provider will instruct you on the discarding procedure and may provide you with an FDA-cleared disposal container called a sharps container. Put your used needles, syringes, or Rebif Rebidose autoinjectors in a sharps container immediately after use. Do not throw away (dispose of) any sharps in your household trash. If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:

• made of a heavy-duty plastic,
• can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
• upright and stable during use,
• leak-resistant, and
• properly labeled to warn of hazardous waste inside the container.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of it. Find out your state or local laws about how you should throw away used needles and syringes. Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. Always keep your disposal container out of the reach of children.

For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: www.fda.gov/safesharpsdisposal

If you will be spending time away from home, you can take your Rebif with you. First, pack the supplies that you'll need for your trip. A handy travel kit that can carry all of your injection supplies is available for free through the MS LifeLines® support program by calling 1-877-447-3243. If a refrigerator is not available while you are traveling, Rebif may be stored at or below room temperature (77°F/25°C) for up to 30 days and away from heat and light. For this reason, the travel kit provides a reusable ice pack to help maintain Rebif syringes at the correct temperature while you travel.

Rebif should be stored refrigerated between 36°F and 46°F (2°C and 8°C). Do not freeze. You should check the temperature of the refrigerator that you are using while traveling to avoid unintentionally freezing Rebif. For small hotel refrigerators, store Rebif away from the unit's cooling element and small freezer compartment.

If you are traveling by car, don't leave Rebif on the dashboard, in the glove compartment, or in the trunk. This is important even if you have it in the insulated pack provided in the travel kit. Keep your syringes with you in the climate-controlled area of the car.

If you are flying, plan to carry your Rebif syringes with you onboard in your carry-on luggage. Be sure to check the latest FAA regulations regarding traveling with injectable medicines. These are subject to change and may require certain documentation.

If you become pregnant while taking Rebif, you should call your doctor right away. You and your doctor will need to decide whether the potential benefit of taking Rebif is greater than the risks to your unborn child.

Yes. When it comes to helping you start and stay on Rebif therapy, MS LifeLines^® is committed to finding affordable access. There are a number of programs available, including as little as $0 co-pay for those eligible. To see if you're eligible for these programs, call 1-877-447-3243, to speak with an MS LifeLines Financial Support Specialist, Monday through Friday, 8 am to 8 pm ET, and Saturday, 9 am to 5 pm ET.

Attention Patients: Federal and state healthcare program beneficiaries are not eligible for the MS LifeLines^® $0 co-pay program. If you participate in a federal or state healthcare program, including Medicare, Medicaid, TRICARE, the Department of Veterans Affairs, the Department of Defense, or any other similar federal or state healthcare program, including any state medical pharmaceutical assistance program, you are not eligible to utilize the MS LifeLines^® $0 co-pay program.