A new comprehensive report on the safety of MS drugs may have doctors rethinking their recommendations.
The results are in, and according to a recent report comparing the safety records of all multiple sclerosis (MS) drugs on the market, Tecfidera took the top safety prize. The report reveals that newer MS drugs received high marks for safety, while older interferon drugs had more reported side effects.
California-based health informatics company AdverseEvents analyzed side effects data from the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) database. The FDA asks that doctors, consumers, and drugmakers report any serious negative health events they or their patients experience while taking an FDA-approved drug.
Using a formula called the “reporting odds ratio” (ROR), analysts compare how often an adverse event (AE) has been reported, regardless of drug, to how often the event has been reported for a specific drug in the FAERS database. This helps safety professionals identify AE and drug pairs with a higher than usual occurrence of a particular side effect, sending up a red flag.
Because the ROR is a ratio that is not affected by length of time a drug has been on the market, the analysts at AdverseEvents were able to compare the oldest MS drugs with the newest and compile accurate results, giving each drug an “RxScore.”
So, comparing the AEs reported for all MS drugs only during the time period since Tecfidera won approval did not affect the outcome, said Keith Hoffman, Vice President of Scientific Affairs at AdverseEvents, in an interview with Healthline. “We have completed that time comparison with other drug classes many times and the overall results stayed the same.”
The RxScore scale ranges from 0 to 100, with higher numbers indicating a greater risk of adverse events. Avonex, Rebif and Betaseron, all interferons, had the worst safety records, with scores between 53 and 55. Copaxone had the fourth highest score at 47.4.
Betaseron had the highest ratio for reports of disability or death, while Avonex users were hospitalized due to AEs the most often.
People taking Avonex reported more malignant tumors, breast cancer diagnoses, and flu-like symptoms than those taking other drugs, while Betaseron users reported more heart attacks, bacterial infections, and liver problems.
Rebif received the worst RxScore, with a higher proportion of negative events including suicidal behavior, optic nerve inflammation, and cancers of the female reproductive system.
Copaxone fared worst for life-threatening allergic reactions and psychiatric symptoms. But Copaxone, FDA-approved in 1996, scored best on measures of several side effects, including cognitive disorders and flu-like symptoms, making it the safest of the older first-line MS drugs.
Tecfidera attained the lowest RxScore of 33 and the lowest ROR of life-threatening events, hospitalizations, disability, or death. It also scored lowest for everything from bacterial infections to optic nerve disorders and liver problems. Overall, Tecfidera had the lowest ROR for 24 out of the 58 side effects the researchers studied.
Gilenya scored second best at 39.4, but users had more cardiac-related AEs, including lowered heart rate, and the drug also scored the worst for vision disorders and skin cancers. Gilenya, FDA-approved in 2010, did not hold the lowest score for any reported AEs.
Aubagio, with the same RxScore as Gilenya, had the highest number of reports of diarrhea, but that’s the only side effect for which it scored the highest, making it among the safest of the MS therapies.
Tysabri scored relatively well but had the highest ROR for cognitive disorders, JC virus positive tests, and secondary progressive MS. The report also concluded that the relationship between Tysabri and primary multifocaleukoencephalothopy, or PML, a rare and deadly brain infection, was confirmed.
Extavia had the worst safety score of any of the new MS drugs at 44.9, and users suffered the most depression, falls, headaches, and injection site reactions.
The FAERS database only examines side effects, not effectiveness. And it cannot predict side effects that may emerge over time.
“We are limited by what is recorded into FAERS,” Hoffman points out. “If a safety concern takes years to manifest after a drug’s approval we will not see those reports until they are filed.”
Although this report is an effective tool for neurologists recommending drugs to their patients, doctors must also consider each drug’s effectiveness. Does it have a track record for reducing relapses, preventing disability, or protecting neurons?
Weighing the risks and benefits is a crucial process when selecting a drug for an MS patient. And everyone’s MS experience is different. Nobody will have all of the reported side effects—or all of the benefits.