To characterize the temporal evolution of immunoglobulin (Ig) levels and the risk of serious infections (SIs) by baseline Ig quartile in the Phase III OPERA I (NCT01247324), OPERA II (NCT01412333) and ORATORIO (NCT01194570) trials of ocrelizumab in multiple sclerosis, and their open-label extensions.

A reduction in serum Ig levels was observed over 6 years of ocrelizumab treatment, with Ig levels remaining above the lower limit of normal (LLN) for the majority of patients. An apparent association between decreased Ig levels and SIs was previously reported.

Serum Ig levels were measured at least every 24 weeks. Baseline IgG, IgM and IgA quartiles (g/L) were determined for OPERA and ORATORIO; Q1 represents patients with lowest baseline levels. LLNs for IgG, IgM and IgA were defined as 5.65g/L, 0.40g/L and 0.70g/L, respectively. Periods of Ig<LLN and SI rates per baseline quartiles were assessed.

Over 6 years of treatment, mean change in IgG levels, g/L (% change) per year by baseline quartile were: Q1, –0.24 (–2.9%); Q2, –0.32 (–3.2%); Q3, –0.40 (–3.6%); Q4, –0.40 (–3.0%) in OPERA, and Q1, –0.23 (–2.9%); Q2, –0.28 (–2.9%); Q3, –0.35 (–3.1%); Q4, –0.51 (–3.8%) in ORATORIO. SI rates per 100 patient-years (95% CI) were: Q1, 1.63 (0.95–2.61); Q2, 1.55 (0.90–2.48); Q3, 1.51 (0.86–2.45); Q4, 1.11 (0.57–1.94) in OPERA, and Q1, 4.04 (2.66–5.87); Q2, 3.81 (2.46–5.62); Q3, 5.39 (3.76–7.50); Q4, 2.17 (1.22–3.59) in ORATORIO. Changes in IgM/IgA levels, and patient demographics and disease characteristics, for each quartile will also be presented.

Patients with lower baseline IgG levels demonstrated less absolute IgG decline versus patients with higher baseline IgG levels. A similar percentage decline was observed across quartiles. Overall, rates of SIs per baseline IgG quartiles were similar and remain low.