Table 3. Clinical trials to study the efficacy of teriflunomide in relapsing forms of MS.

RCT: Randomized control trial, ARR: Absolute risk reduction, IFN-beta-1a: Interferon beta-1 alpha, HR: Hazard ratio, ALT: Alanine amino-transferase, OD: once daily, Gde: Gadolinium-enhanced [109-112]

Miller at al. 2012 [109]; O' Connor et al. 2016 [110]; Miller et al. 2012 [111]; Varmersch et al. 2014  [112]

Clinical Trial	Study Design	Study Participants	Clinical Outcomes	MRI Outcomes	Adverse Effects
TEMSO Miller at al. 2012	Multicenter placebo-controlled double-blind phase III RCT	1088 subjects with MS assigned to 7 mg, 14 mg or placebo for 108 weeks	Lower ARR with teriflunomide    ( 0.37) vs placebo(0.54)	Both teriflunomide doses were superior to placebo in reducing MRI lesions.	More common with teriflunomide- diarrhoea, nausea, hair thinning, elevated liver enzymes
TEMSO extension O' Connor et al. 2016	Multicenter  double-blind phase III RCT	742 patients with RRMS assigned to OD 7mg or 14mg teriflunomide, 9-year long study	ARR improved as compared to core study. ARR=0.198 &0.215 (7&14 mg)	Gde lesions reduced in patients who switched from placebo to teriflunomide	Same as the original study
TOPIC Miller et al. 2014	Randomised double-blind, placebo-controlled phase III trial	618 patients with CIS assigned to OD 14mg or placebo for 108 weeks	Teriflunomide significantly reduced the risk of relapse vs the placebo (14mg (HR 0.574,95% CI, p=0.0087) and 7mg (HR 0.628, p=0.0271))	Teriflunomide reduced the risk of a new MRI lesion vs placebo	Adverse events occurred in atleast 10% of teriflunomide groups and with an incidence 2% higher than placebo were increased ALT, diarrhoea, paraesthesia
TENERE Varmersch et al. 2014	Phase 3 rater-blinded RCT	324 patient with relapsing MS assigned to OD teriflunomide 7 or 14mg or SC IFN-beta-1a 44 microgram	ARR significantly higher with the 7 mg teriflunomide group. No difference was noted in ARR between 14mg or IFN-beta-1a.		Safety profile consistent with previous studies