Contributions
Abstract: P731
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: TOWER (NCT00751881), a phase 3, randomized, placebo-controlled study of teriflunomide in patients with relapsing forms of MS (RMS), demonstrated that, compared with placebo, teriflunomide 14 mg significantly reduced annualized relapse rate (ARR) and risk of 12-week confirmed disability worsening (12w-CDW), consistent with another pivotal teriflunomide trial (TEMSO, NCT00134563). Patients in TOWER had variable treatment duration (48-156 weeks), with the study ending 48 weeks after last patient randomization. This has seemingly led to challenges in conducting comparative analyses of other phase 3 trials of disease-modifying therapies (DMTs), which generally use a fixed 2-year treatment duration, thus leading to possible exclusion of TOWER results in meta-analyses, including health technology assessments.
Objective: To evaluate relapse and disability worsening outcomes from patients in TOWER, over a fixed 2‑year study period.
Methods: In TOWER, patients with RMS were randomized 1:1:1 to receive placebo or teriflunomide 7 mg or 14 mg, and were treated for ≥48 weeks. In this post hoc analysis, ARR and 12w-CDW outcomes were compared between the overall intent-to-treat (ITT) population and a “fixed 2-year study” population (96-week treatment data, based on each patient"s respective randomization date, extracted from TOWER ITT population).
Results: Of the overall ITT population (N=1165), 681 patients (58.5%) met the criteria for the fixed 2‑year study population; patient demographics and baseline disease characteristics were similar for both groups. In the overall ITT population, ARR was reduced in the teriflunomide 14-mg group (n=370) vs placebo (n=388), corresponding to 36.3% rate reduction (95% CI 20.748.8; P=0.0001) whilst, in the 2‑year study population, reduction of ARR in the teriflunomide 14-mg group (n=223) vs placebo (n=228) was 40.2% (95% CI 20.654.9; P=0.0004). The probability of 12w-CDW was significantly reduced in the teriflunomide 14-mg group vs placebo in both the overall ITT and 2‑year study populations, corresponding to a risk reduction of 31.5% (95% CI -0.453.3; P=0.0442) and 38.7% (95% CI ‑0.162.4; P=0.0479), respectively.
Conclusions: Reductions in both ARR and 12w-CDW following treatment with teriflunomide 14 mg (vs placebo) were comparable between the overall ITT population and the fixed 2-year study population in TOWER. Consistency in outcomes supports inclusion of TOWER study results when conducting comparative analyses vs other DMTs.
Disclosure: Study supported by Sanofi Genzyme.
KT: Employee of Sanofi Genzyme.
JM: Employee of Sanofi Genzyme.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).
Abstract: P731
Type: Poster
Abstract Category: Therapy - disease modifying - Tools for detecting therapeutic response
Background: TOWER (NCT00751881), a phase 3, randomized, placebo-controlled study of teriflunomide in patients with relapsing forms of MS (RMS), demonstrated that, compared with placebo, teriflunomide 14 mg significantly reduced annualized relapse rate (ARR) and risk of 12-week confirmed disability worsening (12w-CDW), consistent with another pivotal teriflunomide trial (TEMSO, NCT00134563). Patients in TOWER had variable treatment duration (48-156 weeks), with the study ending 48 weeks after last patient randomization. This has seemingly led to challenges in conducting comparative analyses of other phase 3 trials of disease-modifying therapies (DMTs), which generally use a fixed 2-year treatment duration, thus leading to possible exclusion of TOWER results in meta-analyses, including health technology assessments.
Objective: To evaluate relapse and disability worsening outcomes from patients in TOWER, over a fixed 2‑year study period.
Methods: In TOWER, patients with RMS were randomized 1:1:1 to receive placebo or teriflunomide 7 mg or 14 mg, and were treated for ≥48 weeks. In this post hoc analysis, ARR and 12w-CDW outcomes were compared between the overall intent-to-treat (ITT) population and a “fixed 2-year study” population (96-week treatment data, based on each patient"s respective randomization date, extracted from TOWER ITT population).
Results: Of the overall ITT population (N=1165), 681 patients (58.5%) met the criteria for the fixed 2‑year study population; patient demographics and baseline disease characteristics were similar for both groups. In the overall ITT population, ARR was reduced in the teriflunomide 14-mg group (n=370) vs placebo (n=388), corresponding to 36.3% rate reduction (95% CI 20.748.8; P=0.0001) whilst, in the 2‑year study population, reduction of ARR in the teriflunomide 14-mg group (n=223) vs placebo (n=228) was 40.2% (95% CI 20.654.9; P=0.0004). The probability of 12w-CDW was significantly reduced in the teriflunomide 14-mg group vs placebo in both the overall ITT and 2‑year study populations, corresponding to a risk reduction of 31.5% (95% CI -0.453.3; P=0.0442) and 38.7% (95% CI ‑0.162.4; P=0.0479), respectively.
Conclusions: Reductions in both ARR and 12w-CDW following treatment with teriflunomide 14 mg (vs placebo) were comparable between the overall ITT population and the fixed 2-year study population in TOWER. Consistency in outcomes supports inclusion of TOWER study results when conducting comparative analyses vs other DMTs.
Disclosure: Study supported by Sanofi Genzyme.
KT: Employee of Sanofi Genzyme.
JM: Employee of Sanofi Genzyme.
MSF: Research/educational grant support (Bayer HealthCare, Genzyme); honoraria/consulting fees (Bayer HealthCare, Biogen Idec, EMD Canada, Novartis, Sanofi, Teva Canada Innovation); member of company advisory boards/board of directors/other similar group (Bayer HealthCare, Biogen Idec, Chugai, Merck Serono, Novartis, Opexa Therapeutics, Sanofi, Teva Canada Innovation).