TY - JOUR
T1 - Differential antibody response to COVID-19 vaccines across immunomodulatory therapies for multiple sclerosis
AU - Satyanarayan, Sammita
AU - Safi, Neha
AU - Sorets, Tali
AU - Filomena, Susan
AU - Zhang, Yinan
AU - Klineova, Sylvia
AU - Fabian, Michelle
AU - Horng, Sam
AU - Tankou, Stephanie
AU - Miller, Aaron
AU - Krieger, Stephen
AU - Lublin, Fred
AU - Sumowski, James
AU - Katz Sand, Ilana
N1 - Funding Information:
S.Satyanarayan has no disclosures; N.Safi has no disclosures; T. Sorets has no disclosures; S. Filomena has no disclosures; Y. Zhang has no disclosures; S.Klineova has given non-promotional lectures with Biogen Idec and Alexion and participated on advisory boards for Biogen Idec, Genentech, and Greenwich Biosciences; M. Fabian has no disclosures; S. Horng has no disclosures; S.Tankou has no disclosures; S. Krieger reports consulting or advisory work with Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, MedDay, Novartis, Teva, and TG Therapeutics, nonpromotional speaking with Biogen, EMD Serono, Genentech, and Novartis, and grant and research support from Biogen and Novartis; F.Lublin reports Sources of Funding for Research: Novartis, Actelion, Biogen, Sanofi, NMSS, NIH, Brainstorm Cell Therapeutics. Consulting Agreements/Advisory Boards/DSMB: Biogen, EMD Serono, Novartis, Teva, Actelion/Janssen, Sanofi/Genzyme, Acorda, Roche/Genentech, MedImmune/Viela Bio, Receptos/Celgene/BMS, TG Therapeutics, Medday, Atara Biotherapeutics, Mapi Pharma, Apitope, Orion Biotechnology, Brainstorm Cell Therapeutics, Jazz Pharmaceuticals, GW Pharma, Mylan, Immunic, Population Council, Avotres, Neurogene, Banner Life Sciences. Stock Options: Avotres. Speaker: Sanofi (non-promotional), EMD Serono (non-promotional); A. Miller reports consulting for AbbVie, Health Services, (Caremark), Adamas, Biogen Idec, Bristol Myers Squib/Celgene, Corrona, EMD Serono, Mallinckrodt, Mapi-Pharma, Novartis, Roche/Genentech, nonpromotional speaking with Biogen Idec, EMD Serono, Alexion, Genentech, and has received research support from Genzyme/Sanofi, Mallinckrodt, Novartis, Roche /Genentech, MedDay; J.Sumowski reports consulting or advisory work with Biogen and Genzyme; I. Katz Sand has no disclosures.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/6
Y1 - 2022/6
N2 - Background: Prior studies suggest reduced humoral response to COVID-19 vaccination in immunosuppressed populations. Disease modifying therapies (DMTs) for multiple sclerosis (MS) have variable immunomodulatory effects, and limited data are available for all DMTs. We aimed to determine the impact of DMTs on antibody response to COVID-19 vaccination among MS patients. Methods: Patients with documented COVID-19 vaccination dates and anti-spike antibody results post-vaccination were identified between March-August 2021. Clinical data were retrospectively abstracted from chart review. Deidentified data were analyzed to evaluate antibody response, and multivariable logistic regression analyses were used to identify clinical and demographic predictors of antibody response. Data analysis was completed with SAS Studio, v3.8. Results: A total of 353 individuals had documented COVID-19 vaccine and antibody test dates (58% Pfizer, 38% Moderna, and 4% Johnson & Johnson). Of these 353 patients, 72% developed antibodies, with a mean antibody test interval of 53 days (median 46) post final vaccine dose. 100% of those on no DMT (n = 34), injectables (n = 20), teriflunomide (n = 10), natalizumab (n = 71), and 97.8% of those on fumarates (n = 46/47) had a positive antibody result. One patient on cladribine (n = 1) had a negative antibody result. Of those on sphingosine-1 phosphate (S1P) modulators, 72.4% (n = 21/29) had a positive antibody result. Of those on anti-CD20 therapies, 37.6% (n = 53/141) had a positive antibody result. Multivariate modeling of the total cohort showed anti-CD20 therapy was significantly associated with lower odds of positive antibody response (OR = 0.024, 95% CI 0.01;0.05, p < 0.0001). Among S1P modulators, increased duration of therapy, and not lymphopenia, may be associated with lower odds of positive antibody response. Multivariate modeling of anti-CD20 therapies showed therapy duration < 1 year (OR 8.14, 95% CI 2.896;22.898 p <.0001) and prior COVID-19 infection (OR = 3.95, 95% CI 1.137;13.726, p =.03) were significantly associated with higher odds of a positive antibody response. In patients with recent B-cell data, mean B-cell count was higher in antibody-positive individuals compared to antibody-negative (32.9 vs. 3.9 cells, p =.0056). Conclusion: MS DMTs had variable impact on antibody response with mRNA and viral vector COVID-19 vaccines. All patients on no DMT, interferons, glatiramer acetate, teriflunomide, natalizumab, and nearly all on fumarates had positive antibody responses post-vaccine. S1P modulators and anti-CD20 therapies attenuated antibody response post-vaccine. For patients on anti-CD20 therapies, shorter duration of therapy and prior COVID-19 infection predicted positive antibody response. Further studies are needed to determine clinical significance of antibody testing, development of cellular mediated immunity, and benefits of booster vaccinations.
AB - Background: Prior studies suggest reduced humoral response to COVID-19 vaccination in immunosuppressed populations. Disease modifying therapies (DMTs) for multiple sclerosis (MS) have variable immunomodulatory effects, and limited data are available for all DMTs. We aimed to determine the impact of DMTs on antibody response to COVID-19 vaccination among MS patients. Methods: Patients with documented COVID-19 vaccination dates and anti-spike antibody results post-vaccination were identified between March-August 2021. Clinical data were retrospectively abstracted from chart review. Deidentified data were analyzed to evaluate antibody response, and multivariable logistic regression analyses were used to identify clinical and demographic predictors of antibody response. Data analysis was completed with SAS Studio, v3.8. Results: A total of 353 individuals had documented COVID-19 vaccine and antibody test dates (58% Pfizer, 38% Moderna, and 4% Johnson & Johnson). Of these 353 patients, 72% developed antibodies, with a mean antibody test interval of 53 days (median 46) post final vaccine dose. 100% of those on no DMT (n = 34), injectables (n = 20), teriflunomide (n = 10), natalizumab (n = 71), and 97.8% of those on fumarates (n = 46/47) had a positive antibody result. One patient on cladribine (n = 1) had a negative antibody result. Of those on sphingosine-1 phosphate (S1P) modulators, 72.4% (n = 21/29) had a positive antibody result. Of those on anti-CD20 therapies, 37.6% (n = 53/141) had a positive antibody result. Multivariate modeling of the total cohort showed anti-CD20 therapy was significantly associated with lower odds of positive antibody response (OR = 0.024, 95% CI 0.01;0.05, p < 0.0001). Among S1P modulators, increased duration of therapy, and not lymphopenia, may be associated with lower odds of positive antibody response. Multivariate modeling of anti-CD20 therapies showed therapy duration < 1 year (OR 8.14, 95% CI 2.896;22.898 p <.0001) and prior COVID-19 infection (OR = 3.95, 95% CI 1.137;13.726, p =.03) were significantly associated with higher odds of a positive antibody response. In patients with recent B-cell data, mean B-cell count was higher in antibody-positive individuals compared to antibody-negative (32.9 vs. 3.9 cells, p =.0056). Conclusion: MS DMTs had variable impact on antibody response with mRNA and viral vector COVID-19 vaccines. All patients on no DMT, interferons, glatiramer acetate, teriflunomide, natalizumab, and nearly all on fumarates had positive antibody responses post-vaccine. S1P modulators and anti-CD20 therapies attenuated antibody response post-vaccine. For patients on anti-CD20 therapies, shorter duration of therapy and prior COVID-19 infection predicted positive antibody response. Further studies are needed to determine clinical significance of antibody testing, development of cellular mediated immunity, and benefits of booster vaccinations.
KW - Antibody response
KW - COVID-19
KW - Multiple sclerosis
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85129691929&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2022.103737
DO - 10.1016/j.msard.2022.103737
M3 - Article
C2 - 35533419
AN - SCOPUS:85129691929
VL - 62
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
M1 - 103737
ER -