TECFIDERA Efficacy Compared to Other DMTs Across Clinical Measures of Relapse1

Braune, et al 2018 Study Design and Methodology:

  • A retrospective, observational, propensity score matching (PSM),* comparative effectiveness analysis of data from the German NeuroTransData (NTD) MS registry, a network of 78 neurologists in 153 offices throughout Germany
  • Patients treated with TECFIDERA were matched in a pairwise fashion with patients in groups treated with interferons (n=439), Copaxone (n=535), Aubagio (n=388), the overall (ie, all-comer) Gilenya population (n=457), and the Gilenya EU label population (n=99)
  • 1:1 propensity score matching was used to match measured baseline characteristics of TECFIDERA populations to each comparator population
  • Propensity scores were calculated using multiple logistic regression with the treatment cohort as the dependent variable and the following confounders at index therapy initiation as independent variables: age, sex, disease duration (from first clinical symptom to start of index therapy), treatment history (number of previous therapies), baseline EDSS score and total number of relapses in the past 12 and 24 months (based on actual follow-up period before index therapy initiation) 
  • Non-pairwise censoring was the primary analysis method for all major outcome measurements. However, pairwise censoring was performed as a predefined sensitivity analysis

Study Population:

  • Patients with RRMS aged ≥18 years with a valid EDSS assessment and/or relapse after index therapy initiation
    • For comparisons with interferons, Copaxone, and Aubagio, patients were treatment naive or could have received prior treatment with any of these 3 therapies, other than the therapy being compared
    • For comparisons with the overall (all-comer) Gilenya population, patients were either treatment naive or had switched from pretreatemend with interferons, Copaxone, or Aubagio with a treatment gap of up to 6 months
    • For comparisons with the Gilenya EU-label subgroup, patients were previously treated with interferons, Copaxone, or Aubagio and had an on-therapy relapse within the last 12 months, indicating treatment failure on prior therapy, with a treatment gap of up to 6 months

Outcome Measurements:

  • Primary: Time to first relapse (TTFR)
  • Secondary: ARR, proportion of relapse-free patients at 12 months and 24 months, time to index therapy discontinuation and reasons for discontinuation

Limitations:

  • Results should be interpreted with caution because of the observational and retrospective nature of this study and because no formal sample size was precalculated
  • Results may not be entirely representative of the general RRMS population, because the investigation included only patients from the German NTD registry, a national database
  • PSM is based only on measured confounders and cannot account for unmeasured confounders; hence, there may be hidden biases

Time to First Relapse (TTFR) for TECFIDERA vs Comparator DMTs

TTFR vs Comparator DMTs
TTFR vs Comparator DMTs

Relapse rate based on TTFR was
lower in the TECFIDERA population vs
the interferons, Copaxone, and
Aubagio populations, and similar to
Gilenya populations

ARR for TECFIDERA vs Comparator DMTs

ARR vs Comparator DMTs
ARR vs Comparator DMTs

TECFIDERA had a lower ARR
vs the interferons, Copaxone,
and Aubagio populations, and a
similar ARR to Gilenya

*PSM is a method that helps reduce the impact of confounding and selection/indication biases to better balance the distributions of covariates across treatment groups, approximating a randomized study design.

Covariates in this study included age, gender, disease duration, treatment history, baseline EDSS score, and total number of relapses in the past 12 and 24 months.

Pairwise data are not shown, but can be found in the Braune study manuscript.

§All relapse results from the non-pairwise censored analysis were confirmed by the pairwise censoring relapse results.

TECFIDERA vs Gilenya: Similar Results in Time to First Relapse

Results of the analysis comparing TECFIDERA to Gilenya showed no evidence of a difference in time to first relapse (TTFR) in the all-comer population. TTFR was also similar in patients meeting the EU label criteria for Gilenya and who had failed prior therapy with interferons, Copaxone, or Aubagio with an on-therapy relapse in the last 12 months and a treatment gap of up to 6 months.

TTFR: TECFIDERA vs Gilenya,
All-Comer Population

TTFR: TECFIDERA vs Gilenya, All-Comer
TTFR: TECFIDERA vs Gilenya, All-Comer

Adapted with permission of the authors.

  • 84% of patients receiving TECFIDERA were relapse-free at 12 months vs 81% receiving Gilenya
  • 74% of patients receiving TECFIDERA were relapse-free at 24 months vs 73% receiving Gilenya

TECFIDERA vs Gilenya,
EU Label Population

TECFIDERA vs Gilenya, EU Label Population
TECFIDERA vs Gilenya, EU Label Population

Adapted with permission of the authors.

  • 74% of patients receiving TECFIDERA were relapse-free at 12 months vs 73% receiving Gilenya
  • 57% of patients receiving TECFIDERA were relapse-free at 24 months vs 63% receiving Gilenya

Reasons for discontinuation of therapy

  • Adverse events and patient decision for nonmedical reasons were the main reasons for discontinuation in the TECFIDERA, interferons, Copaxone, Aubagio, and Gilenya populations

Time to discontinuation

  • Time to discontinuation (TTD) was found to be similar between TECFIDERA and interferons, Copaxone, and Aubagio
  • Patients treated with Gilenya had a longer TTD compared to patients treated with TECFIDERA