1. Evaluating the Efficacy and Safety of Transitioning Patients from Natalizumab to Ocrelizumab (OCTAVE) Kyle Smoot, MD, FAAN1, Kiren Kresa-Reahl, MD1, Pavle Repovic, MD, PhD2, Jessica Craddock, MD3, Chiayi Chen, RN, PhD1, Lindsay Lucas, MS1, Tiffany Gervasi-Follmar, MPH1, and Stanley Cohan, MD, PhD1 1Providence Multiple Sclerosis Center, Providence Brain & Spine Institute, Portland, Oregon 2Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, Washington 3Providence Multiple Sclerosis Center, Providence Sacred Heart Medical Center, Spokane, Washington
Figures 1-3. Changes in EDSS, physical MSIS-29 and psychological MSIS-29 from baseline to months 6 and 12 (for patients who have at least 12 months of follow up)
Background
Results
24 patients included in the analysis. 66.7% female with mean age of 44.5 (±10.3), baseline EDSS of 3.5 [2.4, 4.6] and a median of 31 [18,77] NTZ infusions prior to starting OCR have been enrolled between August 2017 and March 2019 (See Table 1).
16 patients have completed the study duration of 12 months. One patient had a relapse at month 12 without MRI correlate. However, the EDSS at 12 months was 5.5 compared to 4.0 at month 9. Another patient had MRI activity without clinical correlate at month 3 (See Table 2). One patient withdrew from study but did not discontinue OCR at Month 3.
There were no significant changes in the EDSS, physical MSIS-29, and psychological MSIS-29 from baseline to months 6 and 12 (See Figures 1-3).
There were 2 possibly related serious adverse events, breast cancer (invasive ductal with one positive lymph note) and acute cystitis. The breast cancer was detected shortly after dose 2, and the patient opted to continue OCR. Mammogram performed 8 months prior to starting OCR was normal.
Infusion reactions were most common with infusion 1 of dose 1. There was a slight increase with dose three, but the numbers are small (See Figure 4).
Natalizumab (NTZ) is an effective therapy for patients with relapsing MS (RMS). However, it is associated with a risk of progressive multifocal leukoencephalopathy (PML) in patients infected with John Cunningham virus (JCV).
Ocrelizumab (OCR), a humanized CD20 antibody, was approved in the US in March 2017 for the treatment of relapsing MS (RMS) and primary progressive MS (PPMS).
Given the efficacy and safety data demonstrated in OPERA I and II, we anticipated that physicians and patients with relapsing MS being treated with NTZ independent of the JCV status would be interested in transitioning to OCR.
Breakthrough disease is well documented in patients electively coming off NTZ to reduce PML risk¹. Therefore, conducting a study to determine if patients on NTZ regardless of their JCV status can be transitioned to OCR safely without disease progression is currently in progress.
Table 2. Efficacy results for patients who have at least 12 months of follow up
Table 1. Demographics and baseline characteristics
Total Number of Patients 24
Age, mean (SD)
44.5 (10.3)
Female, % (n)
66.7 (16)
Disease duration in years, median [IQR]
13 [7, 25]
Total number of NTZ infusions, median [IQR]*
31 [18, 77]
Number of NTZ infusions in the last 12 months, mean (SD) 8
4.2 (1) 11 12
20.8 (5) 13
70.8 (17)
Annualized Relapse Rate in the last 12 months
0.04
Number of relapses in the last 12 months, % (n)
95.8 (23) 1
Number of relapses in the 12 months prior to starting NTZ, % (n)**
36.4 (8)
54.5 (12) 2
9.1 (2)
Primary reason for switching to OCR, % (n)
Lack of efficacy with NTZ
8.3 (2)
PML risk with NTZ
83.3 (20)
Other**
JCV index result, % (n)
Negative
25.0 (6)
Positive
75.0 (18)
JCV index value (for n=18 positive results), mean (SD)
1.84 (1.17)
EDSS, median [IQR]
3.5 [2.4, 4.6]
Physical MSIS-29, mean (SD)*
42.3 (14.7)
Psychological MSIS-29, mean (SD)*
19.7 (6.3)
*For n=23 patients, one missing
**For n=22 patients, two missing
Number of Patients = 16
3 Months
6 Months
9 Months
12 Months
Had a relapse, % (n)
0.0 (0)
6.3 (1)
Annualized Relapse Rate
0.06
With new or enlarging T2 lesions, % (n)* NA
With GAD+ lesions, % (n) (n=15)*
6.7 (1)
*One patient had three new T2 lesions and three GAD lesions at Month 3.
Objective
To present interim data from OCTAVE, a prospective, observational study to evaluate the efficacy and safety of OCR in RMS patients previously treated with NTZ.
Conclusions
In this study, 24 patients have safely transitioned from NTZ to OCR with no cases of PML. No new safety signals were observed as well.
Of the 16 patients followed for 12 months, only 1 patient had MRI changes which occurred at month 3. In addition, only one patient had a relapse during the study.
Therefore, OCR appears to be a safe and effective treatment option for patients transitioning from NTZ.
Methods
Clinically and radiologically stable RMS patients, aged treated with NTZ for ≥ 12 months, were started on OCR 4-6 weeks after last dose of NTZ and followed for 12 months.
Relapse assessment, Expanded Disability Status Scale (EDSS), and MRI were performed prior to starting OCR and at months 3, 6, 9 (no MRI), and 12.
Figure 4. Patients with infusion-related reactions at each infusion
Reference:
West TW, Cree BA. Natalizumab dosage suspension: are we helping or hurting? Annals of neurology. Sep 2010;68(3):
Disclosures: KS has received research support from Biogen, MedDay, and IMS Health and speaking and consulting fees from Biogen, EMDSerono, Genentech, Genzyme, Novartis, and Teva. SC has served on advisory boards or steering committees for Biogen, Novartis, Sanofi Genzyme, and Pear Therapeutics; has received research support from Biogen, Novartis, Sanofi Genzyme, MedDay, and Roche Genentech; has received speaker honoraria from Biogen, Novartis, Sanofi Genzyme, and Roche Genentech. KKR has received speaking honoraria from Biogen, Novartis, and Sanofi Genzyme and research support from Biogen, Novartis, AbbVie, EMDSerono, Roche Genentech, and Sanofi Genzyme and consulting fees from Celgene, EMDSerono and Roche Genentech. PR has received consulting or speaking honoraria from Acorda, Alexion, Biogen, EMD Serono, Genentech, Novartis, Sanofi, and Teva.JC has received consulting or speaking honoraria from Biogen, EMD Serono, and Sanofi Genzyme. CC, LL, and TG have nothing to disclose.