Compared with twice daily (BID) immediate-release topiramate (TPM-IR), the newer once daily (QD) extended-release formulation (TPM-XR) may be better tolerated by patients with migraine and lead to better compliance and more effective migraine prophylaxis, according to results published in the Journal of Comparative Effectiveness Research.
“Based on the evidence, albeit preliminary, that QD TPM-XR is better tolerated than BID TPM-IR and may be more effective in promoting adherence/persistence with treatment, migraine patients who are candidates for TPM-XR treatment include those who have previously failed TPM-IR or another migraine preventive,” wrote study authors, led by Welton O’Neal, PharmD, executive director, head of medical affairs, Supernus Pharmaceuticals, Rockville, MD. “However, TPM-XR candidates should also include those in whom migraine prophylaxis is being initiated since TPM-XR may produce a more favorable trajectory for migraine preventive therapy.”
Topiramate is approved by the FDA for the treatment of pediatric and adult epilepsy, prophylaxis of migraine in adolescents and adults, and for weight management in obese patients in combination with phentermine. TPM-IR has been widely used for over 20 years, and has a well-established safety and tolerability profile.
Dr. O’Neal and colleagues conducted this retrospective pilot study to assess treatment-emergent adverse events (TEAEs) associated with TPM-XR compared with TPM-IR. They identified 485 patients from 23 centers, among whom the majority (58.8%) were prescribed TPM-XR to prevent migraines. In 15 patients, TPM-XR had been prescribed to treat both migraines and obesity, and in 83, for treatment of epilepsy.
In the migraine cohort, most patients were young or middle-aged adults, whereas in the epilepsy cohort, 35.5% were children or adolescents, of whom 11 were being treated concomitantly for seizures and migraine. Both cohorts were comprised primarily of females (migraine 90.1%; epilepsy 61.4%).
Depression, sleep disturbances, and anxiety were the most common comorbidities in the migraine cohort, and, in epilepsy patients, migraine and depression.
In the epilepsy cohort, TPM-XR brought about a 36% relative reduction in the number of seizures (P=0.002). In the migraine cohort, treatment effected clinically significant improvement (greater than or equal to 50% reduction in mean monthly migraine frequency) in 55.3% of patients, a response rate of 40.9%, and a migraine frequency reduction of 100% in 23.9% of patients.
Overall, the most common TEAEs included cognitive symptoms (difficulty finding words, slowed thinking or speech, memory problems, and difficulty concentrating), paresthesia, gastrointestinal problems, and decreased appetite/weight loss. Patients in the migraine cohort had the highest incidence of any TEAE (27%), which were most commonly cognitive symptoms and paresthesia.
In all, 42.1% of the epilepsy cohort and 49.4% of the migraine cohort continued to take TPM-XR for 6 months or more. In addition, 5.1% of the epilepsy cohort and 4.3% of the migraine cohort discontinued treatment due to an inadequate treatment effect.
Migraine patients discontinued treatment most often due to TEAEs (14.5%), followed by obesity patients (13.0%) and the epilepsy cohort (3.8%).
Researchers then conducted a post hoc analysis in 192 patients who had taken TPM-IR prior to TPM-XR. In all, 35 of 39 patients who reported a reason for discontinuation of TPM-IR cited TEAEs, 5 of whom cited an/or inadequate treatment effect.
Compared with previous TPM-IR treatment, the incidence of overall TEAEs with TPM-XR was significantly lower in all patients (40.1% vs 22.4%, respectively; P < 0.001). This was also true in the migraine cohort, with an incidence of 23.4% vs 47.6%, respectively. Further, the incidence of cognitive symptoms was more than 4-fold lower with TPM-XR vs TPM-IR (4.7 vs 20.3%, respectively), and the incidence of paresthesias significantly lower (2.1% vs 7.8%).
“This pilot study was the first evaluation of TPM-XR use in real-world clinical practice. In this patient sample, TPM-XR was used most commonly for migraine prevention and exhibited the treatment effects and types of TEAEs expected of topiramate. TPM-XR was associated with a significantly lower incidence of TEAEs versus previous TPM-IR, largely due to the markedly lower incidence of cognitive symptoms and paresthesia with TPM-XR,” concluded these researchers.
The study was conducted by Indegene Total Therapeutic Management under a research contract with Supernus Pharmaceuticals, Inc., Rockville, MD.