A detailed analysis of relapsing and primary progressive multiple sclerosis (MS) patients in the three Phase 3 trials of Ocrevus (ocrelizumab) showed that the treatment did not significantly increase their risk of infections — serious or otherwise.
Certain infections, including common colds and influenza, were numerically more common among Ocrevus-treated patients, but this had no effect on their risk of all infections, which was similar between the groups studied. Patients with progressive MS, however, had a numerically higher proportion and rate of infection — a finding that may be linked to the older age and higher disability levels in this group.
The findings were recently shared in a poster, “Infections and Serious Infections with Ocrelizumab in Relapsing Multiple Sclerosis and Primary Progressive Multiple Sclerosis,” at the Feb. 23-25 ACTRIMS 2017 Forum in Orlando, Florida. The presentation took place during the Poster Session 1 and Opening Networking Event.
The three clinical trials — OPERA I (NCT01247324) and OPERA II (NCT01412333) studies in relapsing MS, and the ORATORIO trial (NCT01194570) in people with primary progressive disease — were recently described in two publications in the New England Journal of Medicine. But the data presented at ACTRIMS 2017 represent a more detailed analysis of infections than what was published.
Of infections reported in at least 10 percent of relapsing patients, upper respiratory tract infection and nasopharyngitis — the common cold — were more common among those receiving Ocrevus than Rebif (interferon beta-1a). In total, 52.4 percent of Rebif-treated and 58.4 percent of Ocrevus-treated patients experienced infections, with total rates of 67.8 and 84.5 per 100 patient years in the two groups, respectively.
Herpes infections occurred more often in Ocrevus-treated relapsing patients (5.9 percent) than in those taking Rebif (3.4 percent), but with one exception, they were mild or moderate. One patient became hospitalized with a severe genital herpes simplex infection— which was managed with antiviral drugs — but kept using Ocrevus throughout the herpes treatment.
Serious infections occurred in more than twice of Rebif-treated patients — 2.9 percent compared to 1.3 percent in those receiving Ocrevus. Nevertheless, no patients died during the OPERA trials, and none developed opportunistic infections. In addition, only two Ocrevus-treated relapsing patient (0.2 percent) in the two OPERA trials stopped the treatment because of a non-serious infection.
Among progressive patients in the ORATORIO study, the infections — reported in at least 10 percent of all patients — that were more common in Ocrevus treated patients than in controls were upper respiratory tract infection and influenza. This, however, did not influence the total rates of infections, which were 73.8 and 71.7 per 100 patient years in the placebo and Ocrevus-treated groups, respectively. In total, 67.8 percent of placebo, and 69.8 percent of Ocrevus-treated progressive patients experienced infections.
Serious infections were also similar in the two groups, with 5.9 percent in the placebo, and 6.2 percent in the Ocrevus-treated patients. This translated to 2.9 per 100 patient-years in the placebo group, and 3.0 per 100 patient-years in the Ocrevus group.
Among herpes infections, only oral herpes was more common in those receiving Ocrevus (2.3 percent) than in the control group (0.4 percent).
Again, no opportunistic infections were seen, but two Ocrevus-treated patients died because of infections. Researchers conducting the trial deemed the deaths — one from aspiration pneumonia and the other from pneumonia — unrelated to the treatment, but the study’s sponsor, Genentech-Roche, judged the cases to be linked to treatment.
Both patients who died had a disability level of 6.5, as measured by the Expanded Disability Status Scale (EDSS), and no history of immunosuppressant treatment. In the ORATORIO trial, numerically more patients in the placebo group (1.3 percent) withdrew from the study because of infections than those in the Ocrevus-treated group (0.8 percent).
“The proportion of patients with serious infections was numerically lower in patients treated with OCR [Ocrevus] compared with [Rebif] in patients with RMS [relapsing MS] and similar compared with PBO [placebo] in patients with PPMS [primary progressive MS],” the team concluded.