Pharmacokinetics/pharmacodynamics by race: Analysis of a peginterferon β-1a phase 1 study

•Patients who identify as Black are underrepresented in clinical trials•A study of s.c. versus i.m. peginterferon β-1a enrolled 51.5% Black participants•Black and White participants displayed similar pharmacokinetics and pharmacodynamics•Fewer adverse events were reported among Black versus White participants People who identify as Black in the United States are disproportionately affected by multiple sclerosis compared with those who identify as White, yet few Black patients are enrolled in clinical trials for multiple sclerosis, limiting the relevance of current data. In a study that compared pharmacokinetics (what the body does to the drug) and pharmacodynamics (what the drug does to the body) between skin and muscle injections of peginterferon β-1a, >50% of participants identified as Black, enabling a subgroup comparison of Black and White participants. The outcomes were similar between racial groups, with somewhat fewer reports of negative side effects among Black versus White participants. These results support the approved dosage of peginterferon β-1a in Black and White patients and demonstrate the importance of well-balanced, inclusive clinical studies. BackgroundBlack/African American participants are underrepresented in clinical trials for multiple sclerosis but can experience a greater burden of disease than other racial groups in the United States. A phase 1, open-label, crossover study that demonstrated bioequivalence of subcutaneous and intramuscular injection of peginterferon β-1a in healthy volunteers enrolled similar proportions of Black and White participants, enabling a post hoc subgroup analysis comparing these groups.MethodsPeginterferon β-1a (125 μg) was administered by subcutaneous or intramuscular injection, followed by a washout period before a second injection using the alternative method. The primary pharmacokinetic and pharmacodynamic endpoints were maximum observed concentration (Cmax) and area under the concentration-time curve from hour 0 to infinity (AUCinf) of study drug and serum concentration of neop-terin, respectively. Safety and tolerability were included as secondary endpoints.FindingsThis analysis included 70 (51.5%) Black and 59 (43.3%) White participants. Peginterferon β-1a Cmax was 29.8% higher in Black than in White participants following subcutaneous administration but was similar following intramuscular administration. Mean AUCinf was 31.0% and 11.8% greater in Black than in White participants with subcutaneous and intramuscular administration, respectively. Pharmacodynamics and safety signals were similar between groups, although Black participants reported numerically fewer adverse events.ConclusionsNo clinically meaningful differences were identified between Black and White participants related to peginterferon β-1a administration, supporting the approved dose of 125 μg/mL peginterferon β-1a. Future clinical studies should include sufficiently diverse populations to ensure accurate assessments of treatment response.FundingFunding for medical writing support was provided by Biogen (Cambridge, MA, USA). Black/African American participants are underrepresented in clinical trials for multiple sclerosis but can experience a greater burden of disease than other racial groups in the United States. A phase 1, open-label, crossover study that demonstrated bioequivalence of subcutaneous and intramuscular injection of peginterferon β-1a in healthy volunteers enrolled similar proportions of Black and White participants, enabling a post hoc subgroup analysis comparing these groups. Peginterferon β-1a (125 μg) was administered by subcutaneous or intramuscular injection, followed by a washout period before a second injection using the alternative method. The primary pharmacokinetic and pharmacodynamic endpoints were maximum observed concentration (Cmax) and area under the concentration-time curve from hour 0 to infinity (AUCinf) of study drug and serum concentration of neop-terin, respectively. Safety and tolerability were included as secondary endpoints. This analysis included 70 (51.5%) Black and 59 (43.3%) White participants. Peginterferon β-1a Cmax was 29.8% higher in Black than in White participants following subcutaneous administration but was similar following intramuscular administration. Mean AUCinf was 31.0% and 11.8% greater in Black than in White participants with subcutaneous and intramuscular administration, respectively. Pharmacodynamics and safety signals were similar between groups, although Black participants reported numerically fewer adverse events. No clinically meaningful differences were identified between Black and White participants related to peginterferon β-1a administration, supporting the approved dose of 125 μg/mL peginterferon β-1a. Future clinical studies should include sufficiently diverse populations to ensure accurate assessments of treatment response.