Abstract
Introduction: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 741-758 |
| Number of pages | 18 |
| Journal | Neurology and Therapy |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 2022 |
| Externally published | Yes |
Keywords
- ALITHIOS
- Anti-CD20 therapy
- B-cell therapy
- COVID-19
- Ofatumumab
- Post-marketing
- Relapsing multiple sclerosis
- SARS-CoV-2
- Vaccination
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
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COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab. / Cross, Anne H.; Delgado, Silvia; Habek, Mario; Davydovskaya, Maria; Ward, Brian J.; Cree, Bruce A.C.; Totolyan, Natalia; Pingili, Ratnakar; Mancione, Linda; Hu, Xixi; Sullivan, Roseanne; Su, Wendy; Zielman, Ronald; Gupta, Ayan Das; Montalban, Xavier; Winthrop, Kevin.
In: Neurology and Therapy, Vol. 11, No. 2, 06.2022, p. 741-758.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab
AU - Cross, Anne H.
AU - Delgado, Silvia
AU - Habek, Mario
AU - Davydovskaya, Maria
AU - Ward, Brian J.
AU - Cree, Bruce A.C.
AU - Totolyan, Natalia
AU - Pingili, Ratnakar
AU - Mancione, Linda
AU - Hu, Xixi
AU - Sullivan, Roseanne
AU - Su, Wendy
AU - Zielman, Ronald
AU - Gupta, Ayan Das
AU - Montalban, Xavier
AU - Winthrop, Kevin
N1 - Funding Information: Anne H. Cross has received consulting fees, research support, and honoraria from Biogen, Celgene, Bristol Myers Squibb, EMD Serono, Merck, Genentech, Roche, Greenwich Biosciences, Horizon, Janssen (subsidiary of Johnson & Johnson), Novartis, TG Therapeutics, Academic CME, Projects in Knowledge, CME Outfitters, WebMD, Conrad N. Hilton Foundation, The Potomac Center for Medical Education, Consortium of Multiple Sclerosis Centers, and ACTRIMS; serves on the scientific advisory board for ASCLEPIOS I/II for Novartis; has received grants from the National Institutes of Health, the Department of Defense, USA; has held an elected office (secretary) on the Board of Governors of the Consortium of Multiple Sclerosis Centers; was a member of the scientific advisory board of Race to Erase MS, program committee (chair) of ACTRIMS, member of the COVID-19 advisory committee of the National Multiple Sclerosis Society USA and National Multiple Sclerosis Society representative on the Progressive MS Alliance; and has received a patent for “Yablonskiy DA, Sukstansky AL, Wen J, Cross AH. Methods for simultaneous multi-angular relaxometry of tissue using magnetic resonance imaging. Patent 15060-630 (015875).” Silvia Delgado has received fees as a consultant on scientific advisory boards for Novartis and research grants through the University of Miami from EMD Serono, MAPI Pharma, NIH/NINDS, NMSS, and Novartis. Mario Habek participated as a clinical investigator and/or received consultation and/or speaker fees from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva/Teva, Roche, Alvogen, Actelion, Alexion Pharmaceuticals, and TG Pharmaceuticals. Maria Davydovskaya received grants for consulting or speaking fees from Biogen Idec, Celgene/Receptos, Janssen/Actelion, Merck/EMD Serono, Novartis, Roche Sanofi Genzyme, and TG Pharmaceuticals; participated on the advisory board of Biogen Idec, Merck/EMD Serono and served as a president of Medicine Association of Professional and MS centers. Brian J. Ward serves on a scientific advisory board for Novartis and reports personal fees from Novartis for this activity. He is also medical officer for Medicago Inc and holds parts of patents for vaccines targeting influenza, Clostridioides difficile and Schistosoma mansoni. In the last 5 years, he has held academic industry awards with Medicago, MIT Canada, and Aviex Technologies. Bruce A.C. Cree has received personal compensation for consulting from Alexion, Atara Biotherapeutics, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini and received research support from Genentech. Natalia Totolyan has received fees for advisory boards or speaking for Merck and Novartis and institutional grants for conducting clinical trials for Alexion, BIOCAD, Janssen, MAPI Pharma, Merck, Novartis, Receptos, Roche, Sanofi, and TG Therapeutics. Ratnakar Pingili, Linda Mancione, Xixi Hu, Roseanne Sullivan, Wendy Su, Ronald Zielman, and Ayan Das Gupta are employees of Novartis. Roseanne Sullivan is employee of Novartis and has Novartis stock ownership. Xavier Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Medday, Merck, Mylan, NervGen, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, EXCEMED, MSIF, and NMSS. Kevin Winthrop has received consulting fees from Novartis, Roche, and Genentech. Funding Information: We thank the participants of the study. The study sponsor (Novartis Pharma AG, Basel, Switzerland) participated in the design and conduct of the study, data collection, data management, data analysis and data interpretation; preparation, review, and approval of the manuscript, as well as writing of the report and decision to submit the paper for publication. All authors had full access to all study data and took final responsibility for the decision to submit the manuscript for publication. The journal rapid service fee for this publication was funded by Novartis Pharma AG, Basel, Switzerland. We thank Swetha Sirimalla, Anuja Shah and Vaishnavi Khandal (Novartis Healthcare Ltd, Hyderabad, India) for providing medical writing support, which encompassed a literature search, writing of the manuscript, formatting, referencing, preparation of tables and figures per the journal guidelines, and incorporating the authors’ revisions and finalizing the draft for submission, all under the direction of the authors. The assistance of manuscript development and submission was funded by Novartis Pharma AG. Basel, Switzerland. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work, and have given final approval to the version to be published. All authors are responsible for intellectual content and data accuracy. Anne H. Cross and Brian J. Ward contributed to writing and critical revisions of the manuscript. Silvia Delgado, Mario Habek, Maria Davydovskaya, Natalia Totolyan and Xavier Montalban contributed to critical revisions of the manuscript. Bruce A.C. Cree and Kevin Winthrop contributed to data analysis and critical revisions of the manuscript. Ratnakar Pingili, Linda Mancione, Xixi Hu, Roseanne Sullivan, Wendy Su, Ronald Zielman, Ayan Das Gupta, contributed to critical revisions of the manuscript. Anne H. Cross has received consulting fees, research support, and honoraria from Biogen, Celgene, Bristol Myers Squibb, EMD Serono, Merck, Genentech, Roche, Greenwich Biosciences, Horizon, Janssen (subsidiary of Johnson & Johnson), Novartis, TG Therapeutics, Academic CME, Projects in Knowledge, CME Outfitters, WebMD, Conrad N. Hilton Foundation, The Potomac Center for Medical Education, Consortium of Multiple Sclerosis Centers, and ACTRIMS; serves on the scientific advisory board for ASCLEPIOS I/II for Novartis; has received grants from the National Institutes of Health, the Department of Defense, USA; has held an elected office (secretary) on the Board of Governors of the Consortium of Multiple Sclerosis Centers; was a member of the scientific advisory board of Race to Erase MS, program committee (chair) of ACTRIMS, member of the COVID-19 advisory committee of the National Multiple Sclerosis Society USA and National Multiple Sclerosis Society representative on the Progressive MS Alliance; and has received a patent for “Yablonskiy DA, Sukstansky AL, Wen J, Cross AH. Methods for simultaneous multi-angular relaxometry of tissue using magnetic resonance imaging. Patent 15060-630 (015875).” Silvia Delgado has received fees as a consultant on scientific advisory boards for Novartis and research grants through the University of Miami from EMD Serono, MAPI Pharma, NIH/NINDS, NMSS, and Novartis. Mario Habek participated as a clinical investigator and/or received consultation and/or speaker fees from Biogen, Sanofi Genzyme, Merck, Bayer, Novartis, Pliva/Teva, Roche, Alvogen, Actelion, Alexion Pharmaceuticals, and TG Pharmaceuticals. Maria Davydovskaya received grants for consulting or speaking fees from Biogen Idec, Celgene/Receptos, Janssen/Actelion, Merck/EMD Serono, Novartis, Roche Sanofi Genzyme, and TG Pharmaceuticals; participated on the advisory board of Biogen Idec, Merck/EMD Serono and served as a president of Medicine Association of Professional and MS centers. Brian J. Ward serves on a scientific advisory board for Novartis and reports personal fees from Novartis for this activity. He is also medical officer for Medicago Inc and holds parts of patents for vaccines targeting influenza, Clostridioides difficile and Schistosoma mansoni. In the last 5 years, he has held academic industry awards with Medicago, MIT Canada, and Aviex Technologies. Bruce A.C. Cree has received personal compensation for consulting from Alexion, Atara Biotherapeutics, Autobahn, Avotres, Biogen, EMD Serono, Novartis, Sanofi, TG Therapeutics, and Therini and received research support from Genentech. Natalia Totolyan has received fees for advisory boards or speaking for Merck and Novartis and institutional grants for conducting clinical trials for Alexion, BIOCAD, Janssen, MAPI Pharma, Merck, Novartis, Receptos, Roche, Sanofi, and TG Therapeutics. Ratnakar Pingili, Linda Mancione, Xixi Hu, Roseanne Sullivan, Wendy Su, Ronald Zielman, and Ayan Das Gupta are employees of Novartis. Roseanne Sullivan is employee of Novartis and has Novartis stock ownership. Xavier Montalban has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Actelion, Alexion, Bayer, Biogen, Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Medday, Merck, Mylan, NervGen, Novartis, Roche, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, EXCEMED, MSIF, and NMSS. Kevin Winthrop has received consulting fees from Novartis, Roche, and Genentech. Some results from this study were summarized in one research abstract and conference posters, presented at the ECTRIMS 2021 Virtual Congress (October 13–15, 2021). The ALITHIOS (NCT03650114) study was conducted in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice [43], local regulatory requirements, and the principles of the Declaration of Helsinki [44]. The study was approved by ethics committees or institutional review board for each study site, and all patients provided written informed consent before commencing trial-related procedures. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding Information: We thank Swetha Sirimalla, Anuja Shah and Vaishnavi Khandal (Novartis Healthcare Ltd, Hyderabad, India) for providing medical writing support, which encompassed a literature search, writing of the manuscript, formatting, referencing, preparation of tables and figures per the journal guidelines, and incorporating the authors’ revisions and finalizing the draft for submission, all under the direction of the authors. The assistance of manuscript development and submission was funded by Novartis Pharma AG. Basel, Switzerland. Funding Information: The study sponsor (Novartis Pharma AG, Basel, Switzerland) participated in the design and conduct of the study, data collection, data management, data analysis and data interpretation; preparation, review, and approval of the manuscript, as well as writing of the report and decision to submit the paper for publication. All authors had full access to all study data and took final responsibility for the decision to submit the manuscript for publication. The journal rapid service fee for this publication was funded by Novartis Pharma AG, Basel, Switzerland. Publisher Copyright: © 2022, The Author(s).
PY - 2022/6
Y1 - 2022/6
N2 - Introduction: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.
AB - Introduction: The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods: COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results: As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion: COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.
KW - ALITHIOS
KW - Anti-CD20 therapy
KW - B-cell therapy
KW - COVID-19
KW - Ofatumumab
KW - Post-marketing
KW - Relapsing multiple sclerosis
KW - SARS-CoV-2
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=85126116412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126116412&partnerID=8YFLogxK
U2 - 10.1007/s40120-022-00341-z
DO - 10.1007/s40120-022-00341-z
M3 - Article
AN - SCOPUS:85126116412
VL - 11
SP - 741
EP - 758
JO - Neurology and Therapy
JF - Neurology and Therapy
SN - 2193-8253
IS - 2
ER -