Ocrelizumab Linked to Improved Visual Outcomes in Relapsing MS

Deborah Brauser

October 27, 2017

PARIS — Treatment with ocrelizumab (OCR; Ocrevus, Roche) may improve visual outcomes in adult patients with relapsing multiple sclerosis (RMS), new research suggests.

Further analysis of participants with RMS from the phase 3 OPERA 1 and OPERA 2 studies showed that in the pooled intention-to-treat (ITT) group and in a subgroup with visual impairment at baseline, those who received intravenous (IV) OCR had significantly greater improvement on low-contrast letter acuity (LCLA) tests compared with those who received subcutaneous interferon β-1a (IFN; Rebif, EMD Serono).

Dr Laura J. Balcer

In addition, within the visually impaired subgroup, significantly more patients receiving OCR showed at least a 7-letter improvement at 12 weeks compared with the participants receiving IFN.

LCLA "as an exploratory outcome in the OPERA trials was able to capture the treatment benefit of ocrelizumab," Laura J. Balcer, MD, vice-chair of neurology at the School of Medicine at New York University, told attendees here at the 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.

She later told Medscape Medical News that the subgroup with vision problems at baseline showing even greater benefit than the ITT population was gratifying "because this is common in MS" — even in patients who are not aware of the impairment.

"Working on that early in the course, maybe even before they have symptoms, would be important," said Dr Balcer, who is also a professor of neurology, ophthalmology, and population health at New York University.

"Common Clinical Manifestation"

As previously reported, the almost identical OPERA 1 and OPERA 2 trials each had about 800 patients with RMS. All were randomly assigned to receive 600 mg of IV OCR every 6 months for 96 weeks or 44 μg of IFN three times weekly. Main results showed that the OCR groups in OPERA 1 and 2 had a 46% and 47% lower annualized relapse rate, respectively, than the IFN groups (the primary outcome).

Dr Balcer said that the investigators then wanted to assess visual outcomes  because visual impairment is a common clinical manifestation of MS.

In the current analysis, the investigators assessed binocular LCLA by using Sloan letter charts measuring at 2.5% and 1.25% contrast levels. This was done at baseline and every 12 weeks until week 96.

LCLA scores "may reflect axon loss, retina atrophy measured by optical coherence tomography, or OCT, and impact on quality of life," Dr Balcer noted.

Improvement at 12 weeks, shown by at least a 5-, 7-, or 10-letter increase in LCLA score, was also assessed. "A change of at least 7 letters is considered to be clinically meaningful," said Dr Balcer.

The analysis populations included the ITT group (OCR, n = 827; IFN, n = 829) and patients with visual system involvement at baseline, as measured by a visual Function Systems Score of 1 or greater on the Expanded Disability Status Scale (OCR, n = 375; IFN, n = 373).

The mean age for all participants was about 38 years, and 45.2% had visual involvement at baseline.

Visual Improvements

In the ITT population, the mean change from baseline in number correct in LCLA testing (at 25% contrast) was 1.355 in the OCR group at 96 weeks vs 0.012 in the IFN group (P = .03). For those in the two treatment groups with visual system involvement at baseline, the mean changes from baseline were 3.44 vs –0.47, respectively (P < .001).

Time to onset of 12-week confirmed visual improvement, as shown with at least a 7-letter increase, was 36.3% in the OCR/ITT group vs 25.5% in the IFN/ITT group (19–percentage point difference; adjusted hazard ratio [HR], 1.19) — but that missed significance (P = .078).

However, in the visual system subgroup, the patients receiving OCR had a significant HR of 1.54 and a 54% greater increase than those receiving IFN (P = .003).

The proportion of patients with 12-week confirmed improvement during at least 5 of 7 visits was 10.4% of the OCR/ITT patients vs 7.1% of the IFN/ITT patients (odds ratio [OR], 1.50; P = .03). For the visual system involvement subgroup, the proportions were 14.7% vs 6.4%, respectively (OR, 2.72; P ≤ 001).

During the question period after the presentation, Dr Balcer noted that the researchers were not able to assess OCT data, when asked about that measure by session co-chair Ralf Gold, director of the neurological clinic at Ruhr-University Bochum, Germany. However, further investigation is looking at "other metrics of disease activity and progression," including OCT of retinal fiber layer and relapse activity.

Overall, the current analysis showed that vision is an important part of MS, she later told Medscape Medical News. "And it can be captured by a very clinically accessible tool. OPERA was just one of many trials in which low-contrast acuity has been able to detect benefit."

New Generations of Therapy

"I thought this was an exciting study," session co-chair Trevor Kilpatrick, MD, PhD, director of the Melbourne Neuroscience Institute, Australia, told Medscape Medical News.

"The question about the latency of response is really important, and what it's going to tell us potentially about the indirect benefits from ocrelizumab," said Dr Kilpatrick.

"We know this is anti-B cell therapy, but how is it actually leading to some improvement in visual acuity? That's the real cool question here: Does it suggest that there may be even some plasticity that is occurring? And that should be pursued further."

He noted that there are "absolutely" some exciting times ahead for the field.

"I think we're on the cusp of a new generation of perspectives about MS and MS therapy," said Dr Kilpatrick. Not so long ago, "people were just thinking about treating relapsing-remitting MS. Now they're thinking: What's happening in progressive MS? What are the benefits we can provide? And are the new approaches and this new generation of therapies providing opportunities we haven't had in the last 20 years or more?"

The study was funded by F Hoffman-La Roche Ltd. Dr Balcer has received consulting fees from Biogen. Dr Kirkpatrick has disclosed no relevant financial relationships.

7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017. Free Communications session 3, oral presentation 192. Presented October 27, 2017.

Follow Deborah Brauser on Twitter: @MedscapeDeb

For more Medscape Neurology news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.