1. Study Design 121 Relapsing-remitting MS patients randomized to –Stress Management Therapy MS active treatment* 16 individual sessions conducted over 24 weeks Additional 24 weeks of follow-up –Wait-list control* MS treatment as usual for 10+ months 5-hour workshop after 10th month MRIs performed at weeks 8,16,24,32,40, & 48 121 Relapsing-remitting MS patients randomized to –Stress Management Therapy MS active treatment* 16 individual sessions conducted over 24 weeks Additional 24 weeks of follow-up –Wait-list control* MS treatment as usual for 10+ months 5-hour workshop after 10th month MRIs performed at weeks 8,16,24,32,40, & 48 *All patients continued their usual disease-modifying therapy. Mohr DC, et al. Neurology. 2012;79:412-419.

2. Primary endpoint –Cumulative number of new Gd+ lesions at weeks 8, 16, and 24 Secondary endpoints –Cumulative number of new/enlarging T2 lesions –Patients free of new Gd+ and new T2 lesions –T2 volume change –Brain volume change –Stress –Clinical exacerbation Primary endpoint –Cumulative number of new Gd+ lesions at weeks 8, 16, and 24 Secondary endpoints –Cumulative number of new/enlarging T2 lesions –Patients free of new Gd+ and new T2 lesions –T2 volume change –Brain volume change –Stress –Clinical exacerbation Mohr DC, et al. Neurology. 2012;79:412-419. Study Design

3. Reduction in Cumulative Gd+ Lesions and New T2 Lesions (24 Weeks) SMT-MS GroupControl Group (n = 61)(n = 60) P Value Cumulative Gd+ lesions Number 50 th percentile0 0 75 th percentile01.04 Patients free from Gd+ lesions76.8%54.7%.02 Absolute risk reduction: 22.2% New T2 lesions Number 50 th percentile01 75 th percentile13.005 Patients free from new lesions69.5%42.7%.006 Absolute risk reduction: 26.8% SMT-MS GroupControl Group (n = 61)(n = 60) P Value Cumulative Gd+ lesions Number 50 th percentile0 0 75 th percentile01.04 Patients free from Gd+ lesions76.8%54.7%.02 Absolute risk reduction: 22.2% New T2 lesions Number 50 th percentile01 75 th percentile13.005 Patients free from new lesions69.5%42.7%.006 Absolute risk reduction: 26.8% Abbreviation: SMT-MS, stress management therapy – multiple sclerosis. Mohr DC, et al. Neurology. 2012;79:412-419.

4. Changes in Brain Volume * and Stress † SMT-MS GroupControl Group (n = 61)(n = 60)P Value Brain volume % change-0.11 -0.43.01 Stress Life Events Scale Baseline3.1 ± 2.3 2.9 ± 2.3 Week 241.5 ± 1.21.8 ± 1.2.04 Brief Inventory of Perceived Stress Baseline18.2 ± 5.717.3 ± 6.3 Week 2416.3 ± 6.2 17.5 ± 6.2.007 SMT-MS GroupControl Group (n = 61)(n = 60)P Value Brain volume % change-0.11 -0.43.01 Stress Life Events Scale Baseline3.1 ± 2.3 2.9 ± 2.3 Week 241.5 ± 1.21.8 ± 1.2.04 Brief Inventory of Perceived Stress Baseline18.2 ± 5.717.3 ± 6.3 Week 2416.3 ± 6.2 17.5 ± 6.2.007 *Assessed at 48 weeks; † Assessed at 24 weeks. Mohr DC, et al. Neurology. 2012;79:412-419.

5. Clinical Outcomes No significant differences between groups in confirmed exacerbations –Baseline to week 24 22 in Stress Management Therapy-MS (SMT-MS) group vs 22 in control group (P =.84) –Week 24−48 15 in SMT-MS group vs 18 in control group (P =.40) No significant differences between groups in Expanded Disability Status Scale over the trial period (P =.15) No significant differences between groups in confirmed exacerbations –Baseline to week 24 22 in Stress Management Therapy-MS (SMT-MS) group vs 22 in control group (P =.84) –Week 24−48 15 in SMT-MS group vs 18 in control group (P =.40) No significant differences between groups in Expanded Disability Status Scale over the trial period (P =.15) Mohr DC, et al. Neurology. 2012;79:412-419.

6. Follow-Up at 48 Weeks No statistically significant differences remained between groups in terms of Cumulative number of Gd+ lesions Cumulative number of new or enlarging T2 lesions Patients remaining free of Gd+ lesions Patients remaining free of new T2 lesions Levels of stress No statistically significant differences remained between groups in terms of Cumulative number of Gd+ lesions Cumulative number of new or enlarging T2 lesions Patients remaining free of Gd+ lesions Patients remaining free of new T2 lesions Levels of stress Mohr DC, et al. Neurology. 2012;79:412-419.

7. Possible Reasons Why Benefits Were Not Maintained Patients were able to employ the new coping skills as long as they were receiving treatment, but were unable to continue these behavioral changes without ongoing program support Expectations on the part of patients and/or the supportive relationship provided by treatment may have accounted for the benefits of the SMT-MS intervention Patients were able to employ the new coping skills as long as they were receiving treatment, but were unable to continue these behavioral changes without ongoing program support Expectations on the part of patients and/or the supportive relationship provided by treatment may have accounted for the benefits of the SMT-MS intervention Mohr DC, et al. Neurology. 2012;79:412-419.

8. Conclusions Stress management therapy: Effective in reducing new Gd+ lesions and new/enlarging T2 lesions, even in patients with higher disease activity Findings provide firm evidence of the link between stress and increased MRI activity Ongoing stress management therapy may be necessary to sustain the benefit of treatment Stress management therapy: Effective in reducing new Gd+ lesions and new/enlarging T2 lesions, even in patients with higher disease activity Findings provide firm evidence of the link between stress and increased MRI activity Ongoing stress management therapy may be necessary to sustain the benefit of treatment