Comparative study of tolerability and effects on immunoglobulin levels and CD19 cell counts with ocrelizumab vs rituximab in multiple sclerosis
ECTRIMS Online Library. Evertsson B. 09/12/19; 279339; P979
Björn Evertsson
Björn Evertsson
Contributions
Abstract

Abstract: P979

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

B. Evertsson1, T. Hoyt2, A. Christensen2, F. Al Nimer1, J. Foley2, F. Piehl1

1Department of Clinical Neuroscience (CNS), Karolinkska Institute, Stockholm, Sweden, 2Rocky Mountain MS Research Group, Salt Lake City, UT, United States

Background: The anti-CD20 therapies rituximab (RTX) and ocrelizumab (OCR) are increasingly used in MS. Safety concerns include infusion-reactions and increased infections due to interference with the physiological functions of the immune defense. To date no direct comparison of the tolerability and immunosuppressive effects with RTX and OCR have been performed. While the approved dosing for OCR is a repeated 300mg dose at therapy start and 600mg every following 6 months, RTX lacks formal approval for MS and different dosing regimens have been used. In Sweden the most common protocol is with 500 or 1000mg at start of therapy and 500mg every following 6 months.
Aim: To investigate levels of immunoglobulins (IgG/IgM) and CD19 cells in blood in patient initiating RTX or OCR and to record the proportion of patients discontinuing therapy within the first year.
Method: All patients with relapsing-remitting or secondary-progressive MS who initiated RTX at Karolinska University Hospital Huddinge (Sweden) and OCR at Rocky Mountain MS Clinic (UT, USA) were identified through the Swedish MS registry and medical chart review, respectively. Levels of IgG/M, CD19 cells and reasons for therapy discontinuation were extracted from medical charts.
Results: In total 311 Swedish (71% female) and 161 US (59% female) patients were identified. IgG levels dropped with 17mg/dl (CI 4-31) for each OCR infusion, but remained stable with RTX. In contrast, IgM levels dropped to a similar extent in both groups; 12mg/dl (CI 10-15) and 11mg/dl (CI 9-14) for each additional infusion with RTX and OCR, respectively. As expected, CD19 cell counts were greatly suppressed in both groups, but slightly more with OCR. Ten and 15% of patients discontinued treatment with RTX and OCR, respectively (n.s), however, adverse events listed as reason to discontinue were more common with OCR (6.8% vs 2.6%; p=0.026). Only 2.5% and 1.6% discontinued OCR and RTX, respectively, due to lack of effect (n.s).
Conclusion: Both therapies resulted in lowering of IgM, but only OCR led to a significant drop in IgG over the first year of treatment. Although overall rates of therapy discontinuation were similar between RTX and OCR, adverse events were more common with OCR. While the study design and lack of data on efficacy parameters such as imaging preclude robust conclusions on the risk-benefit with the studied therapies, our findings nevertheless indicate that the tolerability and safety with RTX is not inferior to OCR.
Disclosure: Björn Evertsson: Received travel support for conference attendance from Roche
Tammy Hoyt: Nothing to disclose
Angel Christensen: Nothing to disclose
Faiez Al Nimer: Nothing to disclose
John Foley sits on scientific advisory boards for Biogen, Genentech-Roche, Genzyme, Celgene, and EMD Serono. He is also on the Speakers Bureau for Biogen and Genentech-Roche. Dr Foley receives research support from Biogen, Genentech-Roche, Novartis, Genzyme, Mallinckrodt, Adamas and has equity interest in Abreos Bioscience.
Fredrik Piehl has received research grants from Biogen, Genzyme, Merck KGaA and Novartis, and fees for serving as Chair of DMC in clinical trials with Parexel.

Abstract: P979

Type: Poster Sessions

Abstract Category: Therapy - Immunomodulation/Immunosuppression

B. Evertsson1, T. Hoyt2, A. Christensen2, F. Al Nimer1, J. Foley2, F. Piehl1

1Department of Clinical Neuroscience (CNS), Karolinkska Institute, Stockholm, Sweden, 2Rocky Mountain MS Research Group, Salt Lake City, UT, United States

Background: The anti-CD20 therapies rituximab (RTX) and ocrelizumab (OCR) are increasingly used in MS. Safety concerns include infusion-reactions and increased infections due to interference with the physiological functions of the immune defense. To date no direct comparison of the tolerability and immunosuppressive effects with RTX and OCR have been performed. While the approved dosing for OCR is a repeated 300mg dose at therapy start and 600mg every following 6 months, RTX lacks formal approval for MS and different dosing regimens have been used. In Sweden the most common protocol is with 500 or 1000mg at start of therapy and 500mg every following 6 months.
Aim: To investigate levels of immunoglobulins (IgG/IgM) and CD19 cells in blood in patient initiating RTX or OCR and to record the proportion of patients discontinuing therapy within the first year.
Method: All patients with relapsing-remitting or secondary-progressive MS who initiated RTX at Karolinska University Hospital Huddinge (Sweden) and OCR at Rocky Mountain MS Clinic (UT, USA) were identified through the Swedish MS registry and medical chart review, respectively. Levels of IgG/M, CD19 cells and reasons for therapy discontinuation were extracted from medical charts.
Results: In total 311 Swedish (71% female) and 161 US (59% female) patients were identified. IgG levels dropped with 17mg/dl (CI 4-31) for each OCR infusion, but remained stable with RTX. In contrast, IgM levels dropped to a similar extent in both groups; 12mg/dl (CI 10-15) and 11mg/dl (CI 9-14) for each additional infusion with RTX and OCR, respectively. As expected, CD19 cell counts were greatly suppressed in both groups, but slightly more with OCR. Ten and 15% of patients discontinued treatment with RTX and OCR, respectively (n.s), however, adverse events listed as reason to discontinue were more common with OCR (6.8% vs 2.6%; p=0.026). Only 2.5% and 1.6% discontinued OCR and RTX, respectively, due to lack of effect (n.s).
Conclusion: Both therapies resulted in lowering of IgM, but only OCR led to a significant drop in IgG over the first year of treatment. Although overall rates of therapy discontinuation were similar between RTX and OCR, adverse events were more common with OCR. While the study design and lack of data on efficacy parameters such as imaging preclude robust conclusions on the risk-benefit with the studied therapies, our findings nevertheless indicate that the tolerability and safety with RTX is not inferior to OCR.
Disclosure: Björn Evertsson: Received travel support for conference attendance from Roche
Tammy Hoyt: Nothing to disclose
Angel Christensen: Nothing to disclose
Faiez Al Nimer: Nothing to disclose
John Foley sits on scientific advisory boards for Biogen, Genentech-Roche, Genzyme, Celgene, and EMD Serono. He is also on the Speakers Bureau for Biogen and Genentech-Roche. Dr Foley receives research support from Biogen, Genentech-Roche, Novartis, Genzyme, Mallinckrodt, Adamas and has equity interest in Abreos Bioscience.
Fredrik Piehl has received research grants from Biogen, Genzyme, Merck KGaA and Novartis, and fees for serving as Chair of DMC in clinical trials with Parexel.

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