4). A total of 2,376 patients were included in the controlled period of the pivotal clinical trials; of these patients, 1,852 entered the OLE phase. All patients switched to ocrelizumab treatment during the OLE phase. 1,155 patients completed the OLE phase, resulting in approximately 10 years of continuous ocrelizumab treatment (15,515 patient-years of exposure) across the controlled period and OLE phase.
The overall safety profile observed during the controlled period and OLE phase remains consistent with that observed during the controlled period. Tabulated list of adverse reactions Adverse reactions reported in the controlled period of the pivotal clinical trials and derived from spontaneous reporting are listed below in Table 2.
The adverse reactions are listed by MedDRA system organ class and categories of frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).
Within each System Organ Class, the adverse reactions are presented in order of decreasing frequency. Table 2 Adverse reactions MedDRA System Organ Class (SOC) Very common Common Not Known Infections and infestations Upper respiratory tract infection, nasopharyngitis, influenza Sinusitis, bronchitis, oral herpes, gastroenteritis, respiratory tract infection, viral infection, herpes zoster, conjunctivitis, cellulitis Blood and lymphatic system disorders Neutropenia Late onset of Neutropenia2 Respiratory, thoracic and mediastinal disorders Cough, catarrh Investigations Blood immunoglobulin M decreased Blood immunoglobulin G decreased Injury, poisoning and procedural complications Infusion-related reactions1 1 See Descriptions of selected adverse reactions.
2 Observed in the postmarketing setting. Description of selected adverse reactions Infusion-related reactions Across the RMS and PPMS trials, symptoms associated with IRRs included, but are not limited to: pruritus, rash, urticaria, erythema, flushing, hypotension, pyrexia, fatigue, headache, dizziness, throat irritation, oropharyngeal pain, dyspnoea, pharyngeal or laryngeal oedema, nausea, tachycardia.
In controlled trials there were no fatal IRRs. In addition, symptoms of IRR in the post-marketing setting included anaphylaxis. 9% in the interferon beta-1a treatment group (placebo infusion). 5%) and decreased over time to <10% at Dose 4.
The majority of IRRs in both treatment groups were mild to moderate. 1% of ocrelizumab treated patients experienced mild and moderate IRRs, respectively. 1% experienced life- threatening IRRs. 5% in the placebo group. 4%) and decreased with subsequent doses to <10% at Dose 4.
A greater proportion of patients in each group experienced IRRs with the first infusion of each dose compared with the second infusion of that dose. The majority of IRRs were mild to moderate. 4% experienced severe IRRs. There were no life-threatening IRRs.
4. Over the controlled period and OLE phase of the RMS and PPMS clinical trials, patients were given approximately 20 doses of ocrelizumab. Incidence of IRRs decreased to <4% by Dose 4 of the OLE phase in RMS patients and to <5% by Dose 5 of the OLE phase in PPMS patients.
With subsequent doses administered during the OLE phase, incidence of IRR remained low. The majority of IRRs were mild during the OLE phase. 1). 7% vs. 8%, respectively). 5% of patients receiving interferon beta 1a. 9% of patients receiving interferon beta 1a.
9% of patients receiving placebo. 7% of patients receiving placebo. All patients switched to ocrelizumab during the OLE phase in both RMS and PPMS studies. Over the OLE phase in RMS and PPMS patients, the overall risk of SIs did not increase from that observed during the controlled period.
As observed during the controlled period, the rate of SIs in PPMS patients remained higher than that observed in RMS patients. In line with the previous analysis of risk factors for SIs in auto-immune conditions other than MS (see […]