DX53 Switch Analysis of Teriflunomide from Other Multiple Sclerosis Disease Modifying Therapies Ronald O. Bailey, M.D., Nader M. Gemayel, Ph.D., Vu A. Nguyen, M.A., and Carina G. Sprague, LVN Riverside Medical Clinic, Riverside, CA

Table 1: Baseline Demographics and Switch Reasons Figure 1: Patient Outcomes •The percent of patients who relapsed on OBJECTIVES 1.1% teriflunomide was low, all were on prior DISCUSSION Variable N = 95 5.3% 3.2% 1.1% NTZ therapy and occurred at month 6. All had complete recovery after steroid •The ARR for teriflunomide 14mg in this switch study was 0.04 To evaluate the effectiveness and safety of teriflunomide in Age (yr) – mean ± SD 55.4 ± 10.6 treatment and switching back to NTZ. the first switch analysis study. Range 24 to 81 compared to 0.37 in the TEMSO study, 0.32 in the TOWER (Tables 2 and 3) study, and 0.26 in the TENERE study.2-4 This difference may be Female Gender – N (%) 83 (87%) •Patients on prior sub-optimal DMTs due to differences in study design, baseline characteristics, and BACKGROUND were relapse-free on terifluonimide. study duration. Caucasian – N (%) 78 (82%) •One-third of patients on prior NTZ experienced relapse 89.5% •Ten patients (10.5%) reported side requiring steroids. Recurrence of disease activity after NTZ EDSS – mean ± SD 3.5 ± 1.7 effects early in the treatment course •Teriflunomide is an oral once-daily immunomodulatory discontinuation is common and effective therapy after NTZ Range 1 to 8 (within 2 months). Of these, 5 (5.3%) agent with anti-inflammatory properties, that blocks the discontinuation has not been identified. Recent studies reported proliferation of activated B and T lymphocytes.1 discontinued teriflunomide and resumed Disease Duration (yr) – mean ± SD 15.0 ± 10.2 prior DMT. Side effects in the other 5 31% to 60% of patients on prior NTZ experienced relapses after 5-6 •Although the effects of teriflunomide on relapse-related Range 2 to 40 Clinically stable on teriflunomide D/C side effects patients resolved while remaining on switching to fingolimod and 41% to other treatments. D/C relapse (require steroids) D/C pseudo-relapse neurologic sequelae are known, there is no published study teriflunomide. (Tables 3 and 4) •In this study, the incidences of hair thinning (2%), increased evaluating the effectiveness and safety of teriflunomide Prior Therapies – N (%) D/C pregnancy D/C = discontinue due to liver enzymes (2%), diarrhea (2%), and nausea/vomiting (1%) Glatiramer acetate (GA) 70 (73.7%) •Two patients (2.1%) experienced mild when switched from other multiple sclerosis (MS) disease were lower than the incidences reported in the TEMSO study for Interferon β (IFN β) 14 (14.7%) hair thinning (both with onset at month 2) modifying therapies (DMTs). teriflunomide 14mg (13%, 14%, 18%, and 14%, respectively).2 Natalizumab (NTZ) 9 (9.5%) Figure 2: Probability of Remaining on Teriflunomide and resolved within 1 and 3 months, Other orals 2 (2.1%) Therapy over Time respectively, while remaining on teriflunomide. Two (2.1%) had elevated 100% METHODS Primary Reason for Switching – N (%) liver enzymes (>3x ULN), both resolved CONCLUSION Lipoatrophy or injection site reaction 32 (32.6%) within 2 and 3 months, respectively, after Preference for an oral agent 22 (23.2%) 90% discontinuation. (Table 4) •Patients were included in this study if they: Injection or infusion exhaustion 19 (20.0%) 80% 1. Switched to teriflunomide from another MS DMT, and Increase in relapse 10 (10.5%) •Teriflunomide is an effective and well tolerated oral medication for the management of MS. 2. On teriflunomide for at least 6 months (unless JCV positive serology 6 (6.3%) 70% Table 4: Adverse Events Increase in EDSS 5 (5.3%) treatment discontinuation due to side effects, relapse, •Side effects were mild and rarely led to treatment Nabs to IFN β 1 (1.1%) Adverse Events N (%) and/or at the patient’s request) 60% Nabs to NTZ 1 (1.1%) Entire cohort discontinuation. 3. Note: Treatment duration for each patient will vary 50% EDSS > 3 Anxiety 1 (1.1%) as each patient had different teriflunomide start date. Nabs = neutralizing antibodies •A 97% relapse-free rate during the first year of treatment EDSS ≤ 3 40% Diarrhea 2 (2.1%) compares favorably to other DMTs in our clinical practice and •For prior therapy with natalizumab (NTZ), teriflunomide makes teriflunomide a logical choice for first line switch therapy Hair thinning* 2 (2.1%) was given one month after the last NTZ infusion. No Table 2: Clinical Outcomes 30% in the management of MS. washout period was used for conversion of other MS DMTs Probability of Remaining on Therapy Hypotension 1 (1.1%) Outcomes N = 95 20% to teriflunomide. Increased LFTs** 2 (2.1%) 0 5 10 15 20 •Analysis included baseline demographics, reasons for Pseudo-relapse – N (%) 2 (2.1%) Nausea / Vomiting 1 (1.1%) Months REFERENCES switching, pseudo-relapses, relapses requiring steroids Relapse requiring steroids – N (%) 3 (3.2%) Pregnancy 1 (1.1%) treatment, Cox proportional hazards on probability of Annualized relapse rate (ARR) 0.04 LFTs = liver function tests *One resolved after 1 month and one resolved after 3 months 1. Aubagio® Prescribing Information (September 2012) remaining on therapy across time, side effects, and **Both cases resolved 2 and 3 months, respectively, after drug discontinuation 2. O’Connor P, et al. New Engl J Med. 2011;365:1293-1303. % relapse-free 96.8% Table 3: Reasons for Treatment Discontinuation discontinuation rate on teriflunomide. 3. Confavreux C, et al. Lancet Neurol. 2014;13:247-256. Reasons N (%) Comments 4. Vermeersch P, et al. Mult Scler J. Nov 21, 2013. [Epub ahead of print]. 5. Copobianco M, et. al. Neurology. 2014 vol 8 no 10 Supplement P7.206 6. Havla J, et al. Neurology. 2014 vol 8 no 10 Supplement P7.206 RESULTS •Over 50% switched to teriflunomide due to injection- Side effects 5 (5.3%) Reasons: 1 anxiety*, 1 hypotension/diarrhea, 1 associated reasons, almost 25% due to preference for nausea/vomiting*, and 2 increased in LFTs an oral agent, and about 16% due to sub-optimal Statistical Analysis: Simple descriptive statistics were done using Microsoft Excel and Cox Proportional Hazards •Ninety-five patients met the inclusion criteria. All were therapies (increase in relapse or EDSS). (Table 1) Relapse requiring steroids** 3 (3.2%) All were on prior NTZ therapy and occurred at month 6 survival model was performed using Software R. started on teriflunomide 14mg. Baseline demographics Cox Proportional Hazards: •Almost 90% of patients were clinically stable on Pseudo-relapse*** 1 (1.1%) Was on prior NTZ therapy and occurred at month 4 and primary reasons for switching are listed in Table 1. The Cox model estimates the survival probability S(t) of a patient surviving at least until time t, teriflunomide therapy, without any relapse or side via the hazard function defined by: •While the majority of patients were Caucasian, almost effects leading to discontinuation. (Figure 1) Pregnancy 1 (1.1%) Patient discontinued teriflunomide and underwent The hazard function is modeled as a function of input variables (e.g., EDSS score) via the equation: 20% of patients were non-Caucasian (mostly African- accelerated elimination at week 6 of pregnancy and •The probability of patients remaining on teriflunomide American and Hispanics). (Table 1) experienced spontaneous abortion at week 7 at 12 months is almost 90%, regardless of EDSS *Discontinued at patient’s request. Disclosure: •Average duration of therapy was 10.1 ± 4.4 months. score ≤3 or >3. (Figure 2) **All returned back to baseline after steroid treatment and switching back to NTZ ***Both patients returned back to baseline while remaining on teriflunomide. One patient subsequently requested to be switched back to NTZ The authors have nothing to declare