Medicine & Research

What About the Side Effects?

By Helen Tremlett, Ph.D. and Joel Oger, M.D., FRCPC

Drug safety in MS

No drug is absolutely safe. Moreover, there is no known way of completely establishing the safety of a drug before it is prescribed to the general population. Any drug for multiple sclerosis - or any disease for that matter - has to go through fairly rigorous testing, the final stage of which is a large clinical trial. However, those clinical trials are really only able to detect common adverse reactions, also known as side effects. They usually cannot detect the rarer, but sometimes more serious, adverse events. The very controlled conditions under which these clinical trials are conducted are not the same as what occurs in the "real world." Because of that, it is necessary to keep monitoring drugs once they are being prescribed outside a clincial trial. Unfortunately, this is not done in a systematic manner.

Reporting adverse reactions

Most countries have developed what are known as “voluntary adverse drug reporting schemes.” This basically means that the government relies on the goodwill of physicians, pharmacists, nurses or other healthcare providers to report any serious or unexpected adverse drug reactions. In some countries, such as the United States, Canada and the United Kingdom, patients themselves can report adverse drug reactions online. Not everyone finds the time to fill out a report, however. In fact, we know that such methods, while very useful, have a number of limitations. Not all adverse reactions get reported. In addition, not all adverse drug reactions that are reported are really related to the drug in question.

For example, let us say someone with MS develops a certain side effect taking a beta-interferon or glatiramer acetate to treat MS. Who is to say whether the drug caused the side effect or if the person might have developed it anyway? But if a physician, pharmacist or other healthcare provider decides that the drug could have been responsible, and they report it as a reaction, then that reaction will be monitored in other people taking that medication. If more reactions like that one are reported in connection with that particular drug, the medical profession is alerted. They tell their patients about the possible risk and further rigorous studies are conducted.

These adverse drug reports have been the basis for identifying serious reactions and interactions between drugs and have in the past led to drug withdrawals.

Our research in Canada

For our study, we accessed the records of all adverse drug reactions to MS disease-modifying drugs that had been reported within the past 10 years to Health Canada, the federal department responsible for helping Canadians maintain and improve their health. We specifically looked at beta-interferon and glatiramer acetate. We found many of the reported side effects were already known, including liver-related adverse events for beta-interferon, and adverse skin reactions for glatiramer acetate. However, there were some side effects reported in specific groups of patients which stood out.

We found some adverse events reported during pregnancy: two suspected congenital abnormalities, as well as six cases of pregnancy loss in which it is suspected glatiramer acetate played a role. This reaffirms what we already knew. Both beta-interferon and glatiramer acetate remain essentially contraindicated, or advised against, during pregnancy, as there have been no well-controlled studies in humans to adequately assess their safety. We also found adverse events in children younger than 16, including two cases of liver problems and hepatitis.

We looked at who reported the adverse events and found, surprisingly, that a higher-than-expected number were from the patients themselves; most adverse drug reactions unrelated to MS medications had been reported to Health Canada through a pharmacist. This highlights how important it is for patients to recognize and report adverse events.

Things to consider

There are two main limitations of this study. First, adverse drug reactions are likely under-reported. It is estimated that only 10 percent of all serious adverse events actually get reported once a drug has been put on the market. Second, we can never be sure if an adverse event really was related to the drug in question or if it would have happened anyway.

If you think you have developed an adverse reaction to a drug you are taking, make sure you let your doctor or pharmacist know. Encourage them to complete an adverse drug reaction report, if appropriate. Alternatively, you could report the reaction yourself. Whether you or your healthcare provider reports the adverse drug reaction, it could be one step toward preventing others from suffering from the same problem.

Helen Tremlett, Ph.D. and Joel Oger, M.D. conduct their research at the Division of Neurology and the MS Clinic in the department of Medicine at UBC Hospital at the University of British Columbia.

Want to report an adverse drug reaction?

In the US, adverse reactions can be reported to the FDA through its website, www.fda.gov. or call 1-888-463-6332.

In Canada, visit Health Canada at www.hc-sc.gc.ca.

(Last reviewed 7/2009)