Barts-MS rose-tinted-odometer: ★★★★★★★
The first 7-star ‘Teal Blue Monday’ #367588
The next in the series of #ECTRIMS2021 long-term follow-up posts. This is the 7.5 year follow-up of the ocrelizumab OPERA 1&2 (relapsing MS) cohort. The efficacy data looks very impressive.
- Annualised relapse rates well below one in 10 years or 0.1 p.a.
2. 82% of ocrelizumab treated subjects had no confirmed disability progression.
3. Less than 7% of ocrelizumab treated subjects needed a walking stick compared to 10% of subjects randomised to interferon for 2-years before switching to ocrelizumab. Sadly, the 2 years on interferon have come at a price; time really is brain and spinal cord. This data like most contemporary data sets make a strong case for flipping the pyramid.
4. The safety of ocrelizumab looks similar to what it was 2-years ago. The risk of serious infections is 1.73 per 100 patient-years of follow-up; i.e. in 1,000 patients on ocrelizumab, 17 will have a serious infection per year. This needs to be balanced against the COVID-19 data showing a doubling of risk of severe COVID-19 in ocrelizumab-treated subjects and an ~80% chance of not seroconverting when being vaccinated with one of the COVID-19 vaccines.
Unfortunately, no end-organ damage data (brain volume loss) to present, but this will come in time.
It is clear that anti-CD20 therapies are a real game-changer when it comes to the management of MS; i.e. very high efficacy therapies, in terms of switching off MRI activity and relapses, with a relatively good short and long term safety profile.ECTRIMS-2021_OPERA-OLE-7.5-years-Poster_VA3-2
Giovannoni et al. Long-term reduction of relapse rate and confirmed disability progression after 7.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis in the OPERA OLE. ECTRIMS 2021, P723.
Introduction: The efficacy and safety of ocrelizumab (OCR) in relapsing multiple sclerosis (RMS) were demonstrated in the 96-week contro led double-blind period (DBP) of the Phase I OPERA I (NCT01247324) and OPERA I (NCT01412333) trials.
Aims: To assess the efficacy of switching from interferon (IFN) β-1a or maintaining OCR therapy on disease activity and confirmed disability progression (CDP) after 5.5 years of fo low-up in the open-label extension (OLE) of OPERA I and OPERA I.
Methods: In the DBP of OPERA I and OPERA I, patients were randomised to receive OCR or IFN β-1a. Patients completing the DBP either continued OCR (OCR-OCR) or switched from IFN β-1a to OCR (IFN-OCR) when entering the OLE. Adjusted annualised relapse rate (ARR), time to onset of 48-week CDP (CDP48) and time to 48-week confirmed Expanded Disability Status Scale score ≥6.0 (time to require a walking aid) were analysed up to Week 384.
Results: Overa l, 76.3% of patients who entered the OLE period completed OLE Year 5.5. Adjusted ARR decreased year-on-year from the pre-switch year to OLE Year 5.5 in IFN-OCR switchers (pre-switch, 0.20; OLE Year 1, 0.10; OLE Year 5.5, 0.03) and was maintained at low levels in OCR-OCR continuers (pre-switch, 0.12; OLE Year 1, 0.10; OLE Year 5.5, 0.03). Rates of CDP48 were lower in OCR-OCR continuers vs IFN-OCR switchers at the end of the DBP (4.1% vs 8.5% [Δ=4.4%; p<0.001]) and numerica ly lower at OLE Year 5.5 (17.9% vs 21.5% [Δ=3.5%; p=0.118]). Rates of patients requiring a walking aid were lower in OCR-OCR continuers vs IFN-OCR switchers at the end of the DBP (0.8% vs 3.1% [Δ=2.4%; p=0.001]) and numerica ly lower at OLE Year 5.5 (6.6% vs 9.5% [Δ=2.9%; p=0.060]). Over the DBP and OLE periods, the risk of CDP48 was 23% lower (overa l percent of patients with CDP48 in OCR-OCR vs IFN-OCR: 14.5% vs 16.4%; HR [95%CI]: 0.77 [0.60–0.98]; p=0.034) and the risk of requiring a walking aid was 35% lower (overa l percent of patients requiring a walking aid in OCR-OCR vs IFN-OCR: 5.2% vs 7.0%; HR [95%CI]: 0.65 [0.44–0.97]; p=0.034) in OCR-OCR continuers vs IFN-OCR switchers.
Conclusions: Switching from IFN β-1a to ocrelizumab at the start of the OLE period was associated with a rapid and robust reduction in ARR that was maintained through the 5.5-year fo low-up of the OLE period.Compared with patients switching to ocrelizumab at the OLE, patients initiating ocrelizumab 2 years earlier had a significantly reduced risk of requiring a walking aid and 48-week CDP.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.