Final Outcomes from the Teriflunomide TOWER Extension Study: Up to 6 Years of Follow-up (Core Plus Extension) in Patients with Relapsing Forms of MS
Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of MS (RMS). In the randomized placebo-controlled phase 3 TOWER study (NCT00751881), patients with RMS (n=1165) received placebo or teriflunomide 7 mg or 14 mg once daily for ≥48 weeks. TOWER confirmed consistent efficacy on annualized relapse rate (ARR) and disability, and safety profile, observed in other teriflunomide trials. Patients completing the core study could enroll in an open-label extension and continue treatment until teriflunomide was commercially available in their country.
To report final long-term efficacy and safety outcomes from patients treated with teriflunomide in the TOWER core study and its extension.
All patients entering the extension received teriflunomide 14 mg regardless of core study treatment. Efficacy data are reported for the intent-to-treat (ITT) population. The safety population included all randomized patients exposed to medication, analyzed according to treatment received.
In total, 751 patients entered the extension (safety population: placebo/14 mg, n=251; 7 mg/14 mg, n=267; 14 mg/14 mg, n=233). Of these, 549 patients (73%) completed the study treatment period; cumulative durations of teriflunomide exposure for patients across the core study and extension were 529 (placebo/14 mg), 1088 (7 mg/14 mg), and 951 (14 mg/14 mg) patient-years.
In the ITT population (placebo/14 mg, n=253; 7 mg/14 mg, n=265; 14 mg/14 mg, n=233), the adjusted ARR in the extension was 0.193. At Month 60 after core study baseline, mean changes in Expanded Disability Status Scale (EDSS) scores from baseline were <0.03 in all treatment groups.
In the extension, percentages of patients reporting adverse events (AEs, 79%) or AEs leading to treatment discontinuation (7.2%) were similar across treatment groups; the nature of AEs was consistent with those seen in the core study. Serious AEs were reported by <13% of patients in each treatment group. Six deaths were reported: pulmonary tuberculosis (Belarus), pulmonary embolism (China), hematemesis (Tunisia), sepsis (Philippines), and suicide (Romania and USA).
Most patients (73%) entering the TOWER extension completed the study (follow-up period of up to 6 years). EDSS remained stable in the core and extension, and ARR remained <0.2 in the extension; AEs reported were consistent with those in the core study. These data further support the positive benefit-risk profile of long-term teriflunomide treatment for RMS.