Temporal trends in pegloticase infusion reactions across the pre, intra, and post-COVID-19 vaccine eras in U.S. commercial insurance claims (20250232)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cross-sectional

Study drug and medical condition

• Medicinal product name:
  KRYSTEXXA
• Study drug International non-proprietary name (INN) or common name:
  PEGLOTICASE
• Anatomical Therapeutic Chemical (ATC) code:
  (M04AX02) pegloticase

  pegloticase
• Medical condition to be studied:
  Gout

Population studied

• Short description of the study population:
  The study population will include individuals captured in the Optum Market Clarity closed claims database between January 1, 2017, and September 30, 2025. Eligible participants will contribute observable person-time during the study era(s), with follow-up defined based on data availability within the database. Participants may contribute to one or more study era(s) depending on the duration of their observation time.; ; Inclusion Criteria (Summary):; Adults (≥18 years) with continuous 12 month enrolment and no prior use of the index drug were included. Patients initiated pegloticase, rituximab, pegaspargase, or PLD based on diagnosis-specific criteria. Pegloticase and rituximab groups required relevant co-therapy (immunomodulator or methotrexate).
• Age groups:
  • Adults (18 to < 65 years)

    • Adults (18 to < 46 years)
    • Adults (46 to < 65 years)
  • Elderly (≥ 65 years)

    • Adults (65 to < 75 years)
    • Adults (75 to < 85 years)
    • Adults (85 years and over)
• Estimated number of subjects:
  817

Study design details

• Study design:
  Retrospective cohort study using U.S. commercial claims (Jan 2017–Sep 2025) to assess trends in severe infusion reactions among new pegloticase users with immunomodulators. Rates evaluated annually and across COVID-19 periods, with comparator analyses for context.
• Main study objective:
  Primary Objective: ; To estimate annual and era-specific incidence rates of severe pegloticase infusion reactions during the pre-, intra-, and post-COVID-19 mass vaccination periods among patients receiving pegloticase with immunomodulator co-therapy (primary analysis) and pegloticase monotherapy (sensitivity analysis).; secondary objectives:; (1) Negative control (contextualization): Using the same outcome definition and time-period framework, estimate annual/era-specific incidence rates of severe infusion reactions among rituximab initiators to evaluate whether there are broad secular changes in coding, detection, or infusion-care patterns unrelated to PEG exposure.; (2) PEG-containing infused comparators (contextualization): Using analogous design and outcome definitions, estimate annual/era-specific incidence rates of severe infusion reactions among initiators of pegaspargase and pegylated liposomal doxorubicin (PLD) to provide context on whether temporal patterns observed for pegloticase are consistent with other PEG-containing infused products.;
• Comparators:
  The study includes the following comparator groups:; • Rituximab as a negative control (non PEG therapy).; • Pegaspargase and PLD (pegylated liposomal doxorubicin) as PEG-containing comparator therapies.
• Outcomes:
  Primary Outcomes; Among patients receiving pegloticase with immunomodulator co-therapy (primary analysis) and pegloticase monotherapy (sensitivity analysis), the following outcomes will be assessed: Anaphylaxis or anaphylactoid reactions, Acute cardiovascular events (CVEs),including acute myocardial infarction (AMI) and stroke Hospitalization for heart failure (HF),All-cause mortality.; Secondary Outcomes; The same outcomes will be evaluated among patients receiving rituximab (negative control cohort) and pegaspargase or pegylated liposomal doxorubicin (PLD) (PEG-containing comparator cohorts).;
• Data analysis plan:
  Data Analysis Plan; Descriptive statistics will summarize baseline characteristics during the 365-day pre-index period and pegloticase infusion frequency during follow-up. Patient characteristics, healthcare utilization, infusion frequency, and immunomodulator type will be assessed across pre-, intra-, and post-COVID-19 vaccination periods. Variables demonstrating temporal variation will be included as covariates in adjusted analyses. ; Calendar Year-/Era-Based Outcome Estimation:; For each outcome, calendar year-/era-specific event counts and incidence rates will be estimated based on events and person-time accrued within each period. Participants may contribute person-time to multiple years or eras. ; Regression Models for Incidence Rates and IRRs:; Poisson regression models, using log person-time as an offset, will estimate incidence rates, 95% confidence intervals (CIs), and incidence rate ratios (IRRs) across calendar years/eras, adjusting for age, sex, and relevant baseline characteristics. Robust standard errors or negative binomial models will be used if overdispersion is detected.; Comparator Cohorts:; Parallel incidence estimation and regression analyses will be conducted for the rituximab, pegaspargase, and PLD cohorts to evaluate within-drug temporal trends. Comparator analyses are not intended for direct comparisons between drugs.