TY - JOUR
T1 - The wearing-off phenomenon of ocrelizumab in patients with multiple sclerosis
AU - Toorop, A A
AU - van Lierop, Z Y G J
AU - Strijbis, E M M
AU - Teunissen, C E
AU - Barkhof, F
AU - Uitdehaag, B M J
AU - van Kempen, Z L E
AU - Killestein, J
N1 - Funding Information: AAT, ZYGJL, EMMS, ZLEK report no competing interests. CET has served on advisory boards for Roche, has received nonfinancial support in the form of research consumables from ADx NeuroSciences and Euroimmun, and has performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen Prevention Center, Boehringer, Axon Neuroscience, EIP Pharma, PeopleBio, and Roche. FB reports other from Neurology, other from Radiology, other from MSJ, other from Neuroradiology, personal fees from Springer, personal fees and other from Bayer, personal fees from Biogen, grants from Roche, grants from Merck, grants from Biogen, personal fees from IXICO Ltd, other from GeNeuro, grants from IMI-EU, grants from GE Healthcare, grants from UK MS Society, grants from Dutch Foundation MS Research, grants from NWO, grants from NIHR, personal fees from Combinostics, outside the submitted work. BMJU reports personal fees from Genzyme, Biogen Idec, Teva Pharmaceutical Industries, Merck Serono, and Roche. JK has accepted speaker and consulting fees from Merck Serono, Biogen, Roche, Teva Pharmaceutical Industries, Genzyme, and Novartis. Publisher Copyright: © 2021 The Authors
PY - 2022/1
Y1 - 2022/1
N2 - Background: Patients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab. Methods: This was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses. Results: Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1–4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks. Conclusions: The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity.
AB - Background: Patients with multiple sclerosis (MS) who are treated with monoclonal antibodies frequently report an increase of MS-related symptoms prior to the next dose known as the wearing-off phenomenon. The objective of this study was to assess the prevalence and predicting factors of the wearing-off phenomenon in patients with MS using ocrelizumab. Methods: This was a prospective cohort study in patients with MS receiving ocrelizumab ≥1 year. Most participants received B-cell guided personalized extended interval dosing to limit ocrelizumab exposure and hospital visits during the COVID-19 pandemic (cut-off ≥ 10 cells/µL). Participants completed questionnaires during ocrelizumab infusion and 2 weeks thereafter. Demographics, clinical and radiological characteristics, CD19 B-cell counts, and serum neurofilament light (sNfL) levels were collected. Data were analyzed using logistic regression analyses. Results: Seventy-one (61%) out of 117 participants reported the wearing-off phenomenon during ocrelizumab treatment. The most frequently reported symptoms were fatigue, cognitive disability and sensory symptoms. Wearing-off symptoms started < 1 week (11%), 1–4 weeks (49%) or more than 4 weeks (37%) before ocrelizumab infusion. Fifty participants (43%) reported a current wearing-off phenomenon at the first questionnaire. Higher body mass index (threshold BMI ≥ 25) increased the odds of reporting a current wearing-off phenomenon (OR 2.70, 95% CI 1.26 to 5.80, p = .011). Infusion interval, EDSS score, MRI disease activity, clinical relapses, CD19 B-cell counts, and sNfL levels were no predictors. Disappearance of the wearing-off phenomenon occurred in the first week after ocrelizumab infusion in most participants. Participants with a current wearing-off phenomenon significantly improved in self-reported physical and psychological functioning after ocrelizumab infusion. Reporting the wearing-off phenomenon did not influence treatment satisfaction. Forty of 109 participants (37%) reported post-infusion symptoms, such as fatigue, flu-like symptoms or walking difficulties. These post-infusion symptoms started directly or in the first week after ocrelizumab infusion and disappeared within 2 weeks. Conclusions: The wearing-off phenomenon is reported by more than half of patients with MS using ocrelizumab. Only BMI was identified as a predicting factor. The wearing-off phenomenon was not elicited by extending infusion intervals or higher B-cell counts. The wearing-off phenomenon of ocrelizumab therefore does not seem to reflect suboptimal control of MS disease activity.
KW - Extended interval dosing
KW - Multiple sclerosis
KW - Neurofilament light
KW - Ocrelizumab
KW - Wearing-off phenomenon
UR - http://www.scopus.com/inward/record.url?scp=85118876256&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.msard.2021.103364
DO - https://doi.org/10.1016/j.msard.2021.103364
M3 - Article
C2 - 35158470
SN - 2211-0348
VL - 57
SP - 103364
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
M1 - 103364
ER -