Long-term suppression of MRI disease activity with ocrelizumab

Patients receiving ocrelizumab maintained near complete suppression of focal MRI disease activity. Advantages were gained both in patients receiving continuous ocrelizumab and in those who switched to ocrelizumab later. Specifically, both relapsing MS (RMS) and primary progressive MS (PPMS) patients showed a reduction of T2 and T1 lesion volume accumulation as well as reduced global/regional volume loss at the 5^th year of follow-up [1].

In the original, phase 3 OPERA I/II (NCT01247324; NCT01412333) and ORATORIO (NCT01194570) trials, the efficacy and safety of ocrelizumab versus interferon beta-1a (IFN) in RMS and versus placebo in PPMS were demonstrated [2]. In the open-label extension (OLE) period of these studies, the effect of switching to/maintaining ocrelizumab therapy on various MRI measures was assessed. Scans were acquired at the 6^th and 5^th year of follow-up after starting the OLE for RMS and PPMS, respectively. Interim results of 3 years after OLE have already been published [3].

RMS patients receiving continuous ocrelizumab, compared with those who switched to ocrelizumab later, showed no differences in number of T1 gadolinium (Gd)-enhancing and new or enlarging T2 lesions (P=0.617 and P=0.760, respectively), but showed less brain structure volume loss, and significant/nominal differences in lesion volume accumulation. Percentage reduction at the 6^th year of ocrelizumab-ocrelizumab versus IFN-ocrelizumab were:

• whole brain volume (WB): -6.9%, P=0.070;
• cortical grey matter volume (CGM): -6.2%, P=0.047;
• white matter volume (WM): -8.3%, P=0.240;
• thalamus volume (THAL): -21.3%, P<0.001;
• cerebellum volume (CBL): -11.0%, P=0.203;
• T2 lesion volume: -92.3%, P=0.034;
• T1 lesion volume: -11.5%, P=0.502.

PPMS patients initially randomised to ocrelizumab showed no difference in T1 Gd-enhancing lesions, a small difference in new or enlarging T2 lesions (ocrelizumab-ocrelizumab versus placebo-ocrelizumab rate: 0.010 and 0.069; P=0.0145), significant/numerical differences in brain volume loss and lesion volume accumulation. Percentage reduction at the 5^th year of ocrelizumab-ocrelizumab versus placebo-ocrelizumab were:

• WB: -4.9%, P=0.388;
• CGM: -0.3%, P=0.948;
• WM: -3.1%, P=0.741;
• THAL (4^th year): -17.0%, P=0.012;
• CBL (4^th year): -15.7%, P=0.070;
• T2 lesion volume: -70.0%, P<0.001;
• T1 lesion volume: -28.1%, P=0.022.

Switching to/maintaining ocrelizumab therapy showed an almost complete suppression of focal MRI disease activity. Additionally, for both RMS and PPMS patients, reduction of T2 and T1 lesion volume accumulation as well as global/regional volume loss tended to persist.

1. Arnold DL. Long-term suppression of MRI disease activity and reduction of global/regional volume loss: results from OPERA I/II and ORATORIO open-label extension. P407, ECTRIMS 2021 Virtual Congress, 13–15 October.
2. Hauser SL, et al. N Engl J Med 2017;376(3):221–234.
3. Hauser SL, et al. Neurology. 2020;95(13):e1854–e1867.

 

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Posted on 9 December 202125 March 2024