1. NEDA epoch analysis of patients with relapsing multiple sclerosis treated with ocrelizumab: Results from the OPERA I and OPERA II, phase III studies
G Giovannoni, D L Arnold, A Bar-Or, G Comi, H P Hartung, E Havrdova, L Kappos, F Lublin, K Selmaj, A Traboulsee, S Belachew, J Han, L Julian, S L Hauser

2. Background
No Evidence of Disease Activity (NEDA) is a composite measure of the absence of detectable clinical and magnetic resonance imaging (MRI) disease activity in relapsing multiple sclerosis (RMS). However, analyses of NEDA using a re-baseline approach may more closely reflect the effects of disease-modifying treatments.

3. Background (cont’d)
Ocrelizumab (600 mg), which demonstrated a robust effect on MRI activity at 8 weeks in a Phase II study of MS patients, was evaluated for NEDA from baseline and following re-baselining at the time of first MRI (Week 24).

4. Objective
To assess the effect of ocrelizumab on the proportion of patients with NEDA by epoch in the pooled OPERA I and II studies. 

5. Methods
In OPERA I and II, patients were randomized 1:1 to receive 600 mg ocrelizumab every 24 weeks or IFNβ‐1a 44 µg three-times weekly for 96 weeks.
NEDA [defined as the absence of protocol-defined relapses, 12-week confirmed disability progression (CDP), new/enlarging T2 lesions and T1 gadolinium-enhancing lesions] was assessed in the overall intent-to-treat population over the controlled treatment phase (baseline to 96 weeks).
Further analyses evaluated the proportion of patients with NEDA from baseline to Week 48 versus from Week 48 to Week 96, and from baseline to Week 24 versus from Week 24 to Week 96. Brain MRI was undertaken at baseline and at Weeks 24, 48 and 96. 

6. Results
In pooled analyses of OPERA I and II, the proportion of patients with NEDA was increased by 75% with ocrelizumab compared with IFNβ-1a over 96 weeks (47.7% versus 27.1%, P<0.0001).
Compared with IFNβ-1a, the proportion of patients with NEDA was 57% higher with ocrelizumab from baseline to Week 48 (53.5% versus 34%) and 47% higher from Week 48 to Week 96 (85.9% versus 58.6%; both P<0.0001).

7. Results (cont’d)
Compared with IFNβ-1a, the proportion of patients with NEDA was 36% higher with ocrelizumab from baseline to Week 24 (58.3% versus 42.8%) and 76% higher from Week 24 to Week 96 (75.5% versus 42.9%; both P<0.0001).
In the ocrelizumab and IFNβ-1a groups, respectively, 79.8% versus 44.4% of patients with evidence of disease activity during Weeks 0-48 achieved NEDA during Weeks (relative increase with ocrelizumab: 84%; P<0.0001). 

8. Conclusions
A higher proportion of patients reached NEDA at first MRI at Week 24 with ocrelizumab versus IFNβ-1a. After re-baselining, from Week 24 to 96 ocrelizumab treatment further increased the proportion of patients reaching NEDA status by 76%, relative to IFNβ-1a.