Study examines real-world side effects linked to dalfampridine

The most common real-world side effects linked to dalfampridine — sold as Ampyra and with generics available — are similar to those listed on its prescribing label for multiple sclerosis (MS), according to data from a safety surveillance database.

Common side effects included urinary tract infection (UTI), dizziness and MS worsening, consistent with the therapy’s known profile. However, previously unreported adverse events, such as spinal cord injury, also were identified.

Still, information in the database identifies only the occurrence of an adverse event in a patient using dalfampridine; it does not determine conclusively the medication was the cause. In many cases, MS progression itself could be responsible for the adverse event.

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Nevertheless, “this study is of positive significance for the early warning of AEs [adverse events] in dalfampridine,” the researchers wrote, adding that “Clinicians should take full consideration of health status of patients and possible AE, and take necessary measures to reduce or avoid the occurrence of AEs.”

The study, “Post-marketing safety surveillance of dalfampridine for multiple sclerosis using FDA adverse event reporting system,” was published in Frontiers in Pharmacology.

Acorda Therapeutics’ dalfampridine has been approved in the U.S. since 2010 to improve walking in adults with all types of MS. It is thought to work by blocking certain potassium channel proteins to restore normal electrical signaling in nerve cells that have been damaged by the neurodegenerative disease.

Common side effects, listed on the prescribing label from clinical trial experience, include UTIs, insomnia, dizziness, headache, nausea, physical weakness, MS worsening, common cold, and back or throat pain, among others.

But due to the limited number of patients in trials and their specific eligibility criteria, the therapy’s safety profile reported in these studies may not include all possible side effects that may occur in the whole MS patient population.

Why real-world data are important

“Real-world data contribute to a more comprehensive understanding of the safety of dalfampridine,” the researchers wrote.

With this in mind, a team of researchers in China examined the real-world safety profile of dalfampridine by analyzing data from the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS). FAERS contains information submitted by the therapy’s developer about the use and adverse events of an approved medication.

FAERs was designed to support the FDA’s post-marketing surveillance program, wherein therapies that have earned regulatory clearance continue to be monitored for safety after commercialization. It cannot be definitively determined that an adverse event in a particular case was caused by dalfampridine use; it simply associates them in the FAERs database.

From February 2010 to September 2022, more than 4 million adverse events were reported to the system, 44,092 of which (0.97%) were suspected to be caused by dalfampridine products. Most reports came from patients in the U.S. (84%).

Most events were reported in women (74.7%) and between ages 46-65 (63.9%), consistent with the demographics of MS, the researchers noted.

Overall, 335 distinct adverse events possibly linked to dalfampridine were identified, spanning 21 different system organ classes.

The most common side effects of dalfampridine

The most commonly reported side effects — UTIs (8.9%), dizziness (6.4%), and MS worsening (5.1%) — were among those reported in the therapy’s label as the most frequent. Subgroup analyses indicated these three adverse events were more common in women and in the 46-65 age group.

Nervous system disorders was the AE class most commonly reported (28.7%). While those effects could be related to changes in nerve signaling with dalfampridine, they also could arise from MS itself, the authors noted.

However, statistical analyses showed that the class of side effects most strongly associated with dalfampridine was investigations, or laboratory tests and other medical investigations that gave an unusual reading. This was followed by infections/infestations and eye disorders.

Six classes of identified AEs are not included on dalfampridine’s prescribing label. These include injury, poisoning, and procedural complications (9.3%), ear disorders (0.78%), abnormal growths (benign, cancerous, or unspecified, 0.49%), metabolism/nutrition disorders (0.4%), endocrine disorders (0.09%), and reproductive/breast disorders (0.08%).

“It is suggested that dalfampridine may have potential adverse effects on these systems and should be paid attention to in clinical use,” the researchers wrote.

The most significant adverse event linked to dalfampridine

Spinal cord injury in a lower spine area called the cauda equina was found to be the most significant AE linked to dalfampridine, along with low percentage of specific immune cells, called CD8-positive T-cells.

Notably, the first was not reported in the prescribing label. Cauda equina spinal injury “may be related to disease progression, as spinal cord injury is common in MS patient,” the researchers wrote. However, it also is possible that dalfampridine-related nerve signaling changes contribute to this type of injury.

Other adverse events strongly associated with the therapy, particularly certain abnormal results in the urine, also were not part of the safety profile described in the label.

Severe outcomes from AEs were relatively common, accounting for 42% of all reports, and hospitalization was the most frequent severe outcome (31.9%). Less than 0.1% of reports were associated with death.

Most commonly reported side effects linked to death were: aspiration pneumonia, a respiratory infection caused by unintentional inhalation of food into the lungs (12 patients); UTIs (11 patients); a serious brain infection called progressive multifocal leukoencephalopathy (nine patients); and seizures (nine patients).

“In summary, this study … found that the AEs of dalfampridine involved multiple system organ such as nervous system, blood system, urinary system, and some of AEs had gender and age differences,” the team wrote. “We also pointed out some new potential AEs not reported in the instruction and literature.”

Still, “this study is a descriptive study, only a description and analysis of existing data, which cannot reveal the causal relationship between AE and drug-used,” they concluded.