The National Multiple Sclerosis Society
Recently, the U.S. Food and Drug Administration (FDA) made changes to the prescribing information for several of the immunomodulating medications approved for the treatment of MS. People with MS have asked questions about these changes and expressed some concerns about the implications for their physical and emotional health. We are providing this update to describe and explain the changes that have been made.
Indications (purposes, according to the FDA, for which a product is to be used)
The indications for two of the drugs—Avonex and Betaseron—have been modified. The recent modifications are shown in italics.
Interferon beta-1a (Avonex®)Product Efficacy and Stability
Avonex is indicated for the treatment of patients with
relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. Safety and efficacy in patients with chronic progressive multiple sclerosis have not been established.
The FDA made this labeling change based on the findings of the CHAMPS study, published in 2000, which demonstrated that Avonex, when used in individuals who have had a single attack of demyelinating disease consistent with a possible MS diagnosis, can delay the onset of a second attack and thus of clinically definite MS. For more information about the CHAMPS study and its implications, see the Research Bulletin dated February 7, 2003.
Interferon beta-1b (Betaseron®)
Betaseron is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations.
The FDA made this labeling change (from "relapsing-remitting MS" to "relapsing forms" of MS) to extend the use of Betaseron to include individuals with secondary-progressive MS who continue to experience relapses or acute attacks. The label extension came as a result of information from two clinical trials of Betaseron in persons with secondary-progressive MS. For more information about these studies, see the Research Bulletin dated March 19, 2003.
The product efficacy and stability information for one of the drugs has been changed in the following way:
Interferon beta-1a (Rebif®)How Supplied
The FDA added the following paragraph to the section on clinical studies in the Rebif label:
Patients treated with Rebif® 44 mcg sc tiw [44 micrograms subcutaneously three times per week] were more likely to remain relapse-free at 24 and 48 weeks than were patients treated with Avonex® 30 mcg im qw [30 micrograms by intramuscular injection once a week]. This study does not support any conclusion regarding effects on the accumulation of physical disability.
The FDA made this labeling change based on extended results of the EVIDENCE study, a head-to-head study of the two drugs. For more details about this study, see the Research Bulletin dated March 19, 2002.
The FDA also approved label changes concerning the storage of Rebif:
Rebif® may be stored at or below 25° C/77° for up to 30 days and away from heat or light. [Note: Betaseron's labeling was expanded to include room temperature storage in early 2002.]
The information about how the medication is supplied has been changed for one of the medications:
Interferon beta-1a (Avonex®)Warnings and Precautions
The FDA approved a pre-filled syringe for Avonex in May of 2003.
None of the available disease-modifying medications is approved by the FDA for use during pregnancy or nursing. However, the FDA recently changed the pregnancy labeling on glatiramer acetate (Copaxone®) from a Category C to a Category B.
The pregnancy statement for Copaxone now indicates that animal studies have shown no adverse effects on embryofetal development or on delivery or offspring growth and development. It concludes by saying, "There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, glatiramer acetate should be used during pregnancy only if clearly needed."
The interferon beta medications-Avonex, Rebif, and Betaseron, all have Category C ratings, indicating that animal studies have shown some adverse effects on the fetus.
Women who plan to become pregnant should discuss all medications they
are taking with their physician. Any woman who becomes pregnant while taking
one of the disease-modifying medications should contact her physician immediately.
The labeling for each of the interferon beta medications contains a warning statement about depression and suicide or suicide attempts. Patients taking any of these medications are told to report any symptoms of depression and/or suicidal ideation to their prescribing physician.
Interferon beta-1a (Avonex®)Other Medical Problems
The FDA recently added the following statement to the Avonex label:
Additionally, there have been post-marketing reports of depression, suicidal ideation and/or development of new or worsening of pre-existing other psychiatric disorders, including psychosis. Some of these patients improve upon cessation of Avonex dosing.
Post-marketing data include reports from patients and/or their doctors of clinical events that have occurred while the patient was taking the medication. Since these reports occur outside the context of a controlled clinical trial, there is no way to determine the relationship between the event and the medication. This is particularly true for the reported onset of depressive symptoms or other emotional changes, since these types of emotional symptoms are common in people with MS whether or not they are taking an interferon. Independent studies of the incidence of depression in people with MS taking interferon beta medications have not confirmed any relationship between depressive symptoms and the medications.
Regardless of the cause of depressive symptoms or suicidal ideation, however, the correct strategy for people with MS is to report the change immediately to their physician so that the problem can be properly evaluated and treated. The patient and physician can make the decision whether stopping the interferon medication is warranted.
Based on original clinical trial data, labeling for each of the interferon medications recommended liver function tests to determine if the medications were having any negative effects. The FDA has recently added information from post-marketing data to the labels of two of the medications.
Interferon beta-1a (Avonex®)
Important Reminder Concerning Interferon Medications
Dr. Aaron Miller, the Society's Chief Medical Officer, emphasizes the need for periodic liver function testing for all patients taking an interferon medication. He recommends obtaining a baseline evaluation, doing a repeat test after one month on medication, and re-testing every three months thereafter.Additional information about injection site reactions has been added to the labeling of one of the medications.
Interferon beta-1b (Betaseron®)
People who are taking a disease-modifying medication for the first time need to pay careful attention to the printed materials that accompany their medications, and talk over potential benefits, side effects, and complications with their physician. Part of the challenge is that more detailed information about possible complications is included in the physician's prescribing information than in the patient brochures. As a result people sometimes hear about problems that they haven't seen described in the patient materials.
People who have been taking medication for some time also need to
pay careful attention to the package inserts. As post-marketing data
are reported, the FDA will periodically make changes to these printed materials,
with the result that people can learn about issues or problems they had
not heard about when starting the medication. Even those who have been
on a medication for a while should discuss any questions or concerns with
Copyright © 2003, The National Multiple Sclerosis Society