Labeling updates to Ocrevus (ocrelizumab) injection, for intravenous use for the treatment of multiple sclerosis (MS) will be applied.
In August 2022, Genentech updated the Warnings and Precautions section (Section 5) of the prescribing information (PI) to include a new warning for immune-mediated colitis. Health care providers should monitor patients for immune-mediated colitis during Ocrevus treatment, and evaluate promptly if signs and symptoms that may indicate immune-mediated colitis, such as new or persistent diarrhea or other gastrointestinal signs and symptoms, occur. HCPs should use their judgement or consult appropriate specialty care to manage signs and symptoms of colitis.
There are also PI updates to the existing warning language pertaining to progressive multifocal leukoencephalopathy (PML), based on the first cases of PML reported in patients with MS treated with Ocrevus in the postmarketing setting. The risk for PML has been made a stand-alone Warnings and Precautions subsection in Section 5 of the PI. PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. At the first sign or symptom suggestive of PML, healthcare providers should withhold Ocrevus and perform an appropriate diagnostic evaluation. If PML is confirmed, treatment with Ocrevus should be discontinued.
Details about each warning are below.
Immune-mediated colitis
Immune-mediated colitis, which can present as a severe and acute-onset form of colitis, has been reported in patients receiving Ocrevus in the postmarketing setting. Some cases of colitis were serious, requiring hospitalization, with a few patients requiring surgical intervention. Systemic corticosteroids were required in many of these patients. The time from treatment initiation to onset of symptoms in these cases ranged from a few weeks to years.
Progressive multifocal leukoencephalopathy (PML)
PML has occurred in Ocrevus-treated patients who had not been treated previously with natalizumab (which has a known association with PML), were not taking any immunosuppressive or immunomodulatory medications associated with the risk of PML prior to or concomitantly with Ocrevus, and did not have any known ongoing systemic medical conditions resulting in compromised immune system function.
JCV infection resulting in PML has also been observed in patients treated with other anti-CD20 antibodies and other MS therapies.
Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes. MRI findings may be apparent before clinical signs or symptoms. Cases of PML, diagnosed based on MRI findings and the detection of JCV DNA in the cerebrospinal fluid in the absence of clinical signs or symptoms specific to PML, have been reported in patients treated with other MS medications associated with PML. Many of these patients subsequently became symptomatic with PML. Therefore, monitoring with MRI for signs that may be consistent with PML may be useful, and any suspicious findings should lead to further investigation to allow for an early diagnosis of PML, if present. Following discontinuation of another MS medication associated with PML, lower PML-related mortality and morbidity have been reported in patients who were initially asymptomatic at diagnosis compared to patients who had characteristic clinical signs and symptoms at diagnosis. It is not known whether these differences are due to early detection and discontinuation of MS treatment or due to differences in disease in these patients.
