Pregabalin Formulation Effectiveness in Real-World Early Response Extended-release versus immediate-release pregabalin in new patients in routine care for neuropathic pain (PREFER)

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  PREGABALIN
• Study drug International non-proprietary name (INN) or common name:
  PREGABALIN
• Medical condition to be studied:
  Pain
• Additional medical condition(s):
  Peripheral neuropathic pain

Population studied

• Short description of the study population:
  The study population comprises adult patients with neuropathic or neuropathic-dominated pain receiving routine outpatient pain care in Germany who newly initiated treatment with either extended-release (ER) or immediate-release (IR) pregabalin. Eligible patients had prospectively documented baseline information prior to or at treatment initiation and at least one follow-up assessment during the predefined 12-week observation period. Patients with concomitant use of both pregabalin formulations at treatment initiation or with insufficient information to reliably determine treatment exposure were excluded.
• 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)
• Estimated number of subjects:
  1776

Study design details

• Study design:
  Non-interventional target trial emulation using prospectively documented German Pain e-Registry data. Patients initiating ER or IR pregabalin were followed for 12 weeks and balanced by propensity score matching to compare effectiveness, tolerability and treatment-related outcomes.
• Main study objective:
  To compare the effectiveness, tolerability and treatment persistence of extended-release versus immediate-release pregabalin in adults with neuropathic or neuropathic-dominated pain and to characterize treatment benefit under routine clinical care conditions.
• Setting:
  Routine outpatient pain care across participating centres in Germany, based on prospectively documented real-world data from the German Pain e-Registry.
• Comparators:
  Patients initiating extended-release (ER) pregabalin compared with patients initiating immediate-release (IR) pregabalin under routine clinical care conditions.
• Outcomes:
  Effectiveness outcomes included pain intensity, pain-related impairment of daily activities and functioning, health-related quality of life, psychological burden, and neuropathic pain characteristics. Treatment-related outcomes included dose development and optimisation, treatment persistence, and treatment-limiting adverse drug reactions. Prospectively specified secondary analyses assessed Realized Treatment Benefit (RTB) across 12 patient-reported outcomes over the 12-week observation period.
• Data analysis plan:
  Descriptive analyses were performed for baseline characteristics and study outcomes. To reduce confounding and improve comparability between treatment groups, propensity scores were estimated from predefined baseline characteristics and patients initiating ER or IR pregabalin were matched 1:1 using nearest-neighbour propensity score matching. Balance was assessed before and after matching. Comparative analyses evaluated between-group differences in effectiveness, tolerability, dose development and treatment persistence over the predefined 12-week observation period. Longitudinal patient-reported outcomes were analysed at predefined assessment times. Prospectively specified secondary analyses evaluated Realized Treatment Benefit (RTB) by normalizing individual longitudinal treatment trajectories to the improvement achievable from baseline and integrating the normalized trajectories over time. Complementary analyses included the predefined ≥30% RTB responder threshold and standardized between-group effect sizes. All analyses were conducted according to the prospectively specified statistical analysis plan.
• Summary results:
  Following propensity score matching, 888 matched datasets were analysed in each treatment cohort. Compared with IR pregabalin, patients receiving ER pregabalin achieved higher maintenance doses and a greater realized cumulative pregabalin dose over the 12-week observation period. For the predefined primary endpoint, pain-related impairment of daily activities decreased by 2.1±1.7 days/week with ER compared with 1.4±1.6 days/week with IR pregabalin (between-group difference 0.7 days/week; p<0.001; SMD 0.43, 95% CI 0.33–0.52), while improvements across all major patient-reported outcome measures consistently favoured ER pregabalin. Treatment-emergent ADRs occurred less frequently (24.4% vs. 40.5%), ADR-related treatment discontinuations were reduced, and treatment persistence at Week 12 was substantially higher with ER vs. IR pregabalin (80.9% vs. 58.3%; all p<0.001).