Indirect treatment comparison of pegloticase in combination with methotrexate versus nanoencapsulated sirolimus plus pegadricase for the treatment of uncontrolled gout (20260129)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Indirect treatment comparison / evidence synthesis using randomized controlled trial (RCT) data (anchored MAIC)

Study drug and medical condition

• Medicinal product name:
  KRYSTEXXA
• Medicinal product name, other:
  Coadministered with Methotrexate
• Study drug International non-proprietary name (INN) or common name:
  PEGLOTICASE

  METHOTREXATE
• Anatomical Therapeutic Chemical (ATC) code:
  (M04AX02) pegloticase

  pegloticase

  (L04AX03) methotrexate

  methotrexate
• Medical condition to be studied:
  Gout

Population studied

• Short description of the study population:
  Short description of the study population: Adults with uncontrolled gout despite prior xanthine oxidase inhibitor (XOI) therapy, represented by the populations enrolled in four eligible RCTs: C405/C406, MIRROR RCT, COMPARE, and DISSOLVE I/II. The evidence base includes 715 participants across the four trial intention-to-treat (ITT) populations as described in the protocol; no new participants are enrolled in the indirect treatment comparison (ITC).
• Age groups:
  • Adult and elderly population (≥18 years)

    • 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)

Study design details

• Study design:
  Secondary evidence synthesis; anchored matching-adjusted indirect comparison (MAIC) for the primary treatment-response comparison using MIRROR RCT IPD and COMPARE aggregate data.
• Main study objective:
  The primary objective is to estimate the relative treatment effect of pegloticase + methotrexate (MTX) versus NASP on treatment response during month 6 among adults with uncontrolled gout. Treatment response is maintaining sUA <6 mg/dL for ≥80% of the assessment period. Additional supportive analyses evaluate month 3 and months 3 & 6 combined.
• Setting:
  Secondary analysis of existing RCT evidence in adults with uncontrolled gout. No prospective enrollment, direct patient contact, or new individual-level data collection will be undertaken.; Interventions: Pegloticase + methotrexate (8 mg IV Q2W + oral MTX 15 mg/week); NASP (ImmTOR 0.15 mg/kg + pegadricase 0.2 mg/kg IV Q4W)
• Comparators:
  NASP (nanoencapsulated sirolimus plus pegadricase; investigational comparator)
• Outcomes:
  Primary: treatment response at month 6, defined as maintaining serum uric acid (sUA) <6 mg/dL for ≥80% of the assessment period. Supportive: treatment response at month 3 and months 3 and 6 combined.
• Data analysis plan:
  Primary anchored MAIC using MIRROR RCT IPD and COMPARE aggregate data. MIRROR will be reweighted to match COMPARE on age, BMI, baseline sUA, and baseline tophi; weighted logistic regression with robust variance will estimate the adjusted log-OR, reported as ORs with 95% confidence intervals (CIs). Sensitivity analyses assess broader covariate adjustment (sex and race), exclusion of participants with missing baseline covariates, and removal of population adjustment. Binary outcomes use odds ratios (ORs); sUA change from baseline (CFB) uses mean differences (MDs). Results are reported with 95% CIs for MAIC.
• Summary results:
  Protocol-stage feasibility assessment indicates that treatment response has the strongest cross-trial comparability and supports an anchored MAIC using MIRROR RCT and COMPARE. Final comparative ITC results are not yet available.