Contributions
Abstract: P573
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Largely asymptomatic, decreased transient heart rate (HR) is an expected pharmacodynamic effect of fingolimod (Gilenya®) initiation; heart block may also rarely occur. US prescribing information requires first-dose observation (FDO) of HR and blood pressure for ≥6 hours in patients initiating fingolimod. FDO can be conducted in clinics; with the Gilenya@Home program, most US patients initiate fingolimod at home.
Objectives: Assess if low baseline HR before initiating fingolimod was an indicator of adverse events (AEs), such as second-degree atrioventricular (2°AV) block, emergency room (ER) monitoring or documented bradycardia.
Methods: Retrospective, anonymized patient FDO data were collated from Gilenya@Home (Oct 2014-Jul 2017) and Gilenya assessment network clinics (Jul 2010-Dec 2016). Extended monitoring was conducted per product label or if HR was ≤45 beats per minute (bpm) at 6 hours. Patients attended the ER for overnight monitoring, if required. Pre-dose baseline HR was assessed retrospectively for patients initiating fingolimod in-home or in-clinic who had new-onset 2°AV block, ER monitoring or documented bradycardia.
Results: Data were collated for 5572 in-home visits and 15,025 in-clinic FDO procedures. Baseline HR (mean±standard deviation) was similar for the overall groups of patients initiating fingolimod in-home and in-clinic (74.8±12.2 bpm vs 74.2±11.4 bpm). Baseline HRs for in-home patients with 2°AV block (74.3±13.7 bpm; n=4 [0.1%]) or who attended the ER (70.4±13.4 bpm; n=15 [0.3%]) were similar to the HR for the overall in-home group. Baseline HRs for in-clinic patients with 2°AV block (76.8±8.4 bpm; n=9 [0.1%]) or who attended the ER (73.4±12.8 bpm; n=129 [0.9%]) were similar to the HR for the overall in-clinic group. Baseline HRs for in-home and in-clinic patients with documented bradycardia (64.4±8.1 bpm; n=20 [0.4%] and 65.3±12.4 bpm; n=10 [0.1%], respectively) were lower than the HRs for the respective overall groups.
Conclusions: Pre-first dose baseline HR for patients who had 2°AV block or attended the ER fell within the overall population range, but were lower for those with bradycardia, whether in-home or in-clinic. These data provide further evidence that first-dose AEs with fingolimod occur in a low percentage of patients, regardless of clinical setting. Analysis of individual-level data may determine whether there is a pre-dose HR threshold below which first-dose adverse cardiac effects are more likely.
Disclosure: John Osborne, medical director of the Gilenya@Home program, has received honoraria for educational programs that he has provided on behalf of Novartis as well as consultation fees for Gilenya@Home. Brandon Brown, Xiangyi Meng, Nina Jaitly, Wendy Su and Jamie Weiss are employees of Novartis Pharmaceuticals Corporation.
Abstract: P573
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Introduction: Largely asymptomatic, decreased transient heart rate (HR) is an expected pharmacodynamic effect of fingolimod (Gilenya®) initiation; heart block may also rarely occur. US prescribing information requires first-dose observation (FDO) of HR and blood pressure for ≥6 hours in patients initiating fingolimod. FDO can be conducted in clinics; with the Gilenya@Home program, most US patients initiate fingolimod at home.
Objectives: Assess if low baseline HR before initiating fingolimod was an indicator of adverse events (AEs), such as second-degree atrioventricular (2°AV) block, emergency room (ER) monitoring or documented bradycardia.
Methods: Retrospective, anonymized patient FDO data were collated from Gilenya@Home (Oct 2014-Jul 2017) and Gilenya assessment network clinics (Jul 2010-Dec 2016). Extended monitoring was conducted per product label or if HR was ≤45 beats per minute (bpm) at 6 hours. Patients attended the ER for overnight monitoring, if required. Pre-dose baseline HR was assessed retrospectively for patients initiating fingolimod in-home or in-clinic who had new-onset 2°AV block, ER monitoring or documented bradycardia.
Results: Data were collated for 5572 in-home visits and 15,025 in-clinic FDO procedures. Baseline HR (mean±standard deviation) was similar for the overall groups of patients initiating fingolimod in-home and in-clinic (74.8±12.2 bpm vs 74.2±11.4 bpm). Baseline HRs for in-home patients with 2°AV block (74.3±13.7 bpm; n=4 [0.1%]) or who attended the ER (70.4±13.4 bpm; n=15 [0.3%]) were similar to the HR for the overall in-home group. Baseline HRs for in-clinic patients with 2°AV block (76.8±8.4 bpm; n=9 [0.1%]) or who attended the ER (73.4±12.8 bpm; n=129 [0.9%]) were similar to the HR for the overall in-clinic group. Baseline HRs for in-home and in-clinic patients with documented bradycardia (64.4±8.1 bpm; n=20 [0.4%] and 65.3±12.4 bpm; n=10 [0.1%], respectively) were lower than the HRs for the respective overall groups.
Conclusions: Pre-first dose baseline HR for patients who had 2°AV block or attended the ER fell within the overall population range, but were lower for those with bradycardia, whether in-home or in-clinic. These data provide further evidence that first-dose AEs with fingolimod occur in a low percentage of patients, regardless of clinical setting. Analysis of individual-level data may determine whether there is a pre-dose HR threshold below which first-dose adverse cardiac effects are more likely.
Disclosure: John Osborne, medical director of the Gilenya@Home program, has received honoraria for educational programs that he has provided on behalf of Novartis as well as consultation fees for Gilenya@Home. Brandon Brown, Xiangyi Meng, Nina Jaitly, Wendy Su and Jamie Weiss are employees of Novartis Pharmaceuticals Corporation.