Evaluating the Tolerability and Safety of Switching from Rituximab to Ocrelizumab: Infusion Related Reactions in Relapsing Forms of Multiple Sclerosis (P4.2-015)

Objective: To assess the frequency and severity of infusion related reactions (IRRs) in patients with relapsing forms of multiple sclerosis switching from rituximab (RTX) to ocrelizumab (OCR). Background: OCR is more humanized and has increased antibody-dependent cell-mediated cytotoxicity than RTX. Safety in transitioning from RTX to OCR is unknown in regards to IRRs. Design/Methods: Patients with ≥2 courses of RTX consented into either a prospective SWITCH group that received OCR on Days 1, 15, and week 24 or a COMPARATOR group (n=100 each) who stayed on RTX for two infusions at the Rocky Mountain MS Center at University of Colorado. Primary outcome was IRR frequency. Factors impacting IRRs were described using generalized estimating equation models. Results: Both groups had similar baseline characteristics with regard to age, gender, disease duration, number of prior DMTs and doses/time on RTX. Unadjusted differences showed 14% of COMPARATOR and Day 1 SWITCH patients had any IRRs (p=1.000). Compared to COMPARATOR, day 15 SWITCH patients only had 4% IRRs (p=0.005) and 12% at week 24(p=0.647). No IRRs of Grade ≥3 were present in either group. We explored factors that affected IRRs in the COMPARATOR group, the risk of IRRs decreased by 45% with each doubling in the number of infusions after adjusting for age, gender, MS disease duration, and BMI(p=0.0389). For Day 1 of the SWITCH patients, IRRs occurred in 5.4% (3/56) if CD19 and/or CD20 were ≤1% but 26.2% (11/42) if >1% with the risk of IRRs increasing by a factor of 3.87 after adjusting for the number of prior RTX infusions, time since last RTX infusion, age, gender, MS disease duration, and BMI (p=0.02). Conclusions: IRRs are similar with RTX and OCR suggesting that it is safe to switch between them. IRRs appear to be related at least in part to B cell levels. Disclosure: Dr. Alvarez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with consulting fees from Biogen, Celgene, Genentech, Genzyme, Novartis, Teva, and TG Pharmaceuticals. Dr. Alvarez has received research support from Acorda, Biogen, Genentech, Novartis, and the Rocky Mountain MS Center. Dr. Nair has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Astellas. Dr. Nair has received research support from Biogen, Novartis, Genentech, and Gilead Sciences. Dr. Shelton has nothing to disclose. Dr. Selva has nothing to disclose. Dr. Voge has nothing to disclose. Dr. Zanganeh has nothing to disclose. Dr. Sillau has nothing to disclose. Dr. Vollmer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Academic CME, Alcimed, Anthem Blue Cross, Genentech/Roche, Biogen IDEC, Novartis, CellGene, Epigene, Rocky Mountain MS Center, GLG Consulting, Ohio Health, TG Therapeutics, Topaz Therapeutics, Dleara Lawyers, Teva. Dr. Vollmer has received research support from Teva, NIH/NINDS, Rocky Mountain MS Center, Actelion, Roche/Genentech, UT Southwestern, TG Therapeutics.