Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (Varenicline solution) nasal spray and Lifitegrast 5% ophthalmic solution for the treatment of dry eye disease

MAIC Analysis: Trial Overview

MAIC, matching-adjusted indirect comparison.
1. White D. et al. J Manag Care Spec Pharm. 2023;29:69–79; 2. Signorovitch JE. et al. Value Health. 2012;15:940–947; 3. Choy E. et al. Arthritis Res Ther. 2019;21:32; 4. Visco DM. et al. J Manag Care Spec Pharm. 2022;28:892–902.

Study Design

BID, twice daily; STS, Schirmer’s test score.
1. Wirta D. et al. Ophthalmology. 2022;129:379–387; 2. White D. et al. J Manag Care Spec Pharm. 2023;29:69–79; 3. Sheppard J. et al. Ophthalmology. 2013;121:475–483; 4. Tauber J. et al. Ophthalmology. 2015;122:2423–2431.

Endpoints Common to Both Trials

  • Mean change from baseline in STS
  • Mean change from baseline in EDS

Outcomes at 2 weeks were compared among studies and ONSET-2 outcomes at 4 weeks were compared with OPUS-1 and OPUS-2 outcomes at 6 weeks.

EDS, eye dryness score; STS, Schirmer’s test score.
White D. et al. J Manag Care Spec Pharm. 2023;29:69–79.

Limitations

  • MAIC analyses are post-hoc indirect comparisons and comparative efficacy is ideally evaluated in head-to-head randomized trials.
  • The validity of MAIC analyses is dependent upon the quality of source studies, and MAICs can only compare outcomes which are assessed using similar methodologies.
  • While MAIC can remove or reduce observed cross-trial differences, unobserved factors may result in residual confounding.
  • Attempts to minimize very large differences can produce weighted datasets with small effective sample sizes which preclude meaningful comparisons.
  • Additionally, current MAIC methodologies do not provide a mechanism for adjustment in differences in time points assessed across studies.

ONSET-2 vs Lifitegrast Trials Results

Baseline Characteristics With Weighting

  • Matching-adjusted indirect comparison (MAIC) is a validated and widely accepted statistical methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent of head-to-head trial outcomes.1,2
  • Baseline characteristic imbalances are adjusted by weighting individual patient data on all available clinically relevant baseline characteristics to create an adjusted dataset that matches the aggregate data of the comparator on the characteristics.1
  • This minimizes imbalances among patient characteristics between study samples that could bias unadjusted cross-study comparisons of treatment outcomes.1
1. Visco DM. et al. J Manag Care Spec Pharm. 2022;28:892–902; 2. White D. et al. J Manag Care Spec Pharm. 2023;29:69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5%

Overview of Weighted Factors Used to Match Baseline Data

MAIC, matching-adjusted indirect comparison; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5% Results

Efficacy Outcome Measures

Trial outcomes: Mean change in STS from baseline

Weighted results of ANCOVA models assessing the LS mean change from baseline in STS for ONSET-2 and OPUS-1. p-values are for treatment vs control at each time point.
ANCOVA, analysis of covariance; CI, confidence interval; LS, least squares; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5% Results

Efficacy Outcome Measures

MAIC outcomes: Mean change in STS from baseline

Weighted results of ANCOVA models assessing the LS mean change from baseline in STS for ONSET-2 and OPUS-1.
ANCOVA, analysis of covariance; CI, confidence interval; LS, least squares; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5% Results

Efficacy Outcome Measures

Trial outcomes: Mean change in EDS from baseline

Weighted results of ANCOVA models assessing the LS mean change from baseline in EDS for ONSET-2 and OPUS-1. EDS was not included as a matching variable. Unweighted baseline EDS values for ONSET-2: 58.52 mm and 58.11 mm for VNS and control, respectively. Baseline EDS values for OPUS-1: 40.20 mm and 41.60 mm for Lifitegrast and control, respectively. p-values are for treatment vs control at each time point.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; LS, least squares; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5% Results

Efficacy Outcome Measures

MAIC outcomes: Mean change in EDS from baseline

Weighted results of ANCOVA models assessing the LS mean change from baseline in EDS for ONSET-2 and OPUS-1. EDS was not included as a matching variable. Unweighted baseline EDS values for ONSET-2: 58.52 mm and 58.11 mm for VNS and control, respectively. Baseline EDS values for OPUS-1: 40.20 mm and 41.60 mm for Lifitegrast and control, respectively.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; LS, least squares; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-1 Phase 3 of Lifitegrast 5% Results

Summary of MAIC Analysis

  • Statistically significant difference in mean change from baseline STS for all comparisons
    • VNS at 2 and 4 weeks compared to Lifitegrast at 2 and 6 weeks, respectively
  • Statistically significant difference in mean change from baseline EDS
    • VNS at 2 and 4 weeks compared to Lifitegrast at 2 and 6 weeks, respectively
EDS, eye dryness score; MAIC, matching-adjusted indirect comparison; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White D. et al. J Manag Care Spec Pharm. 2023;29:69–79.

Study Results

ONSET-2 vs OPUS 2

ONSET-2 of VNS 0.03 mg vs. OPUS-2 Phase 3 of Lifitegrast 5%

Overview of Weighted Factors Used to Match Baseline Data

*The ONSET-2 dataset was subset to include only patients with baseline EDS ≥40 for the OPUS-2 MAIC.
EDS, eye dryness score; MAIC, matching-adjusted indirect comparison; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg and OPUS-2 Phase 3 of Lifitegrast 5%

Efficacy Outcome Measures

Trial Outcomes: Mean Change from Baseline STS

Weighted results of ANCOVA models assessing the LS mean change from baseline in STS for ONSET-2 and OPUS-2. p-values are for treatment vs control at each time point.
ANCOVA, analysis of covariance; CI, confidence interval; LS, least squares; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-2 Phase 3 of Lifitegrast 5%

Efficacy Outcome Measures

MAIC Outcomes: Statistically Significant Difference in Mean Change from Baseline STS

Weighted results of ANCOVA models assessing the LS mean change from baseline in STS for ONSET-2 and OPUS-2.
ANCOVA, analysis of covariance; CI, confidence interval; LS, least squares; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg and OPUS-2 Phase 3 of Lifitegrast 5%

Efficacy Outcome Measures

Trial Outcomes: Mean Change from Baseline EDS

Weighted results of ANCOVA models assessing the LS mean change from baseline in EDS for ONSET-2 and OPUS-2. p-values are for treatment vs control at each time point.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; LS, least squares; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-2 Phase 3 of Lifitegrast 5%

Efficacy Outcome Measures

MAIC Outcomes: Mean Change from Baseline EDS

Weighted results of ANCOVA models assessing the LS mean change from baseline in EDS for ONSET-2 and OPUS-2.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; LS, least squares; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29(1):69–79.

ONSET-2 of VNS 0.03 mg vs. OPUS-2 Phase 3 of Lifitegrast 5%

Summary of MAIC Analysis

    • Statistically significant difference in mean change from baseline STS
      • VNS at 2 and 4 weeks compared to Lifitegrast at 2 and 6 weeks, respectively
    • Not statistically significant difference in mean change from baseline EDS
      • VNS at 2 weeks compared to Lifitegrast at 2 weeks
    • Statistically significant difference in mean change from baseline EDS
      • VNS at 4 weeks compared to Lifitegrast at 6 weeks
EDS, eye dryness score; MAIC, matching-adjusted indirect comparison; STS, Schirmer’s test score; VNS, Varenicline solution nasal spray.
White DE. et al. J Manag Care Spec Pharm. 2023;29:69–79.