Contributions
Abstract: P1251
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a favourable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). The rate of herpes zoster (HZ) seen in patients with MS is approximately 6/1,000 patient-years(Arvin, 2015). Given the immunomodulatory effects of DMF, it has been questioned whether DMF-treated patients may have an increased incidence of HZ infection.
Objectives: To determine whether DMF treatment in patients with RRMS is associated with an increased incidence of HZ infection using cumulative case counts and the cumulative postmarketing reporting rate.
Methods: A cumulative search of the Biogen global safety database (GSD) through 31 December 2016 was performed to determine reporting frequency of HZ and HZ-related infections. The GSD includes serious adverse events (SAEs) from the clinical trial setting and both non-serious and SAEs from the post-marketing setting. A disproportionality comparison of herpes events with DMF from April 2013 through December 2016 employing the Empirical Bayes Method in the Food and Drug Administration Adverse Event Report System (FAERS) database was also performed.
Results: As of 31 December 2016, an estimated 241,031 patients (355,562 patient-years) had received DMF in the post marketing setting; of these 102,101 patients (126,784 patient-years) were in the European Economic Area. A total of 914 HZ events were reported in 897 cases; 268 events were confirmed by healthcare providers (HCPs) (54 serious and 214 non-serious). The cumulative reporting rate for HZ-related infections was estimated as 2.51/1,000 patient-years (95% CI: 2.35-2.68) using all reports and 0.72/1,000 patient-years (95% CI: 0.64-0.82) for HCP-confirmed reports in post-marketing reporting of DMF-treated patients. The cumulative reporting rate for HZ disseminated was estimated as 0.008/1,000 patient-years (95% CI: 0.002-0.025) using all reports and also HCP-confirmed reports. Additionally, the disproportionality analysis utilizing the FAERS database did not identify any increased risk in DMF-treated patients compared with other drugs.
Conclusions: The cumulative postmarketing reporting rates of HZ was lower than the reporting rate in patients with MS. Overall, this analysis yielded no evidence of an increased risk of HZ in DMF-treated patients to date.
Supported by: Biogen.
Disclosure: Jerome Hanna: employee of and holds stock/stock options in Biogen
Claudia Prada: employee of and holds stock/stock options in Biogen
Nicholas Everage: employee of and holds stock/stock options in Biogen
Sirisha Kalari: employee of and holds stock/stock options in Biogen
Pam Jayia: employee of and holds stock/stock options in Biogen
Priya Singhal: employee of and holds stock/stock options in Biogen
Karen Smirnakis: employee of and holds stock/stock options in Biogen
Veronica Englishby: employee of and holds stock/stock options in Biogen
Abstract: P1251
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Delayed-release dimethyl fumarate (DMF) has demonstrated a favourable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). The rate of herpes zoster (HZ) seen in patients with MS is approximately 6/1,000 patient-years(Arvin, 2015). Given the immunomodulatory effects of DMF, it has been questioned whether DMF-treated patients may have an increased incidence of HZ infection.
Objectives: To determine whether DMF treatment in patients with RRMS is associated with an increased incidence of HZ infection using cumulative case counts and the cumulative postmarketing reporting rate.
Methods: A cumulative search of the Biogen global safety database (GSD) through 31 December 2016 was performed to determine reporting frequency of HZ and HZ-related infections. The GSD includes serious adverse events (SAEs) from the clinical trial setting and both non-serious and SAEs from the post-marketing setting. A disproportionality comparison of herpes events with DMF from April 2013 through December 2016 employing the Empirical Bayes Method in the Food and Drug Administration Adverse Event Report System (FAERS) database was also performed.
Results: As of 31 December 2016, an estimated 241,031 patients (355,562 patient-years) had received DMF in the post marketing setting; of these 102,101 patients (126,784 patient-years) were in the European Economic Area. A total of 914 HZ events were reported in 897 cases; 268 events were confirmed by healthcare providers (HCPs) (54 serious and 214 non-serious). The cumulative reporting rate for HZ-related infections was estimated as 2.51/1,000 patient-years (95% CI: 2.35-2.68) using all reports and 0.72/1,000 patient-years (95% CI: 0.64-0.82) for HCP-confirmed reports in post-marketing reporting of DMF-treated patients. The cumulative reporting rate for HZ disseminated was estimated as 0.008/1,000 patient-years (95% CI: 0.002-0.025) using all reports and also HCP-confirmed reports. Additionally, the disproportionality analysis utilizing the FAERS database did not identify any increased risk in DMF-treated patients compared with other drugs.
Conclusions: The cumulative postmarketing reporting rates of HZ was lower than the reporting rate in patients with MS. Overall, this analysis yielded no evidence of an increased risk of HZ in DMF-treated patients to date.
Supported by: Biogen.
Disclosure: Jerome Hanna: employee of and holds stock/stock options in Biogen
Claudia Prada: employee of and holds stock/stock options in Biogen
Nicholas Everage: employee of and holds stock/stock options in Biogen
Sirisha Kalari: employee of and holds stock/stock options in Biogen
Pam Jayia: employee of and holds stock/stock options in Biogen
Priya Singhal: employee of and holds stock/stock options in Biogen
Karen Smirnakis: employee of and holds stock/stock options in Biogen
Veronica Englishby: employee of and holds stock/stock options in Biogen