DMTs and vaccine response in MS: the evidence to date


An Israeli study recently reported a significantly impaired humoral response to COVID-19 vaccination in patients with multiple sclerosis receiving certain disease-modifying therapies (DMT) (Achiron et al. Ther Adv Neurol Disord 2021;14:17562864211012835). In that study, protective humoral immunity following administration of the Pfizer vaccine was observed in 100% of patients treated with cladribine, but only 22.7% of those on ocrelizumab and 3.8% of those receiving fingolimod. (See also Few vaccine responders with fingolimod, ocrelizumab, NeuroSens, April 23, 2021.)

A number of additional studies and case reports have now been published on the humoral response to COVID vaccination in patients on DMTs. The following summarizes what has been reported.

A retrospective study in Italy reported a positive anti-Spike Ab test in 62.5% of fingolimod patients and 37.5% of ocrelizumab patients >2 weeks after vaccination with the Pfizer or Moderna mRNA vaccines (Guerrieri et al. J Neurol 2021; epublished 26 June 2021). No association was found between the serological response and factors such as WBC count or timing of dosing and vaccination.

The Strasbourg group looked at the IgG index following administration of the Pfizer or Moderna vaccine (Bigaut et al. Rev Neurol (Paris), epublished 16 June 2021). The median IgG index was significantly lower in patients treated with an anti-CD20 monoclonal antibody (4.8) or sphingosine 1-phosphate (S1P) receptor modulator (16.5) compared to other DMTs (1116) or no DMT (1272).

A case series found a blunted humoral response to the Pfizer vaccine during treatment with ocrelizumab compared to healthy controls (Gallo et al. Neurol Sci 2021, epublished 15 June 2021). Anti-spike IgG titres were expressed as binding antibody units (BAU). The geometric mean IgG response post-vaccination with ocrelizumab was 4.9 to 175 BAU/mL at 7 days (vs. 2010 in healthy controls), <4.81 to 32.6 BAU/mL at 14 days (vs. 192.3) and <4.81 to 60 at 21 days (vs. 259.5). On a similar note, ocrelizumab has been reported to reduce the likelihood of generating an antibody response to SARS-CoV-2 infection in two recent studies (van Kempen et al. JAMA Neurol 2021;78:880-882. Conte WL. Mult Scler Relat Disord 2021;52:103014), which is consistent with what has been previously reported (Zabalza et al. Eur J Neurol 2020, epublished 19 December 2020).

A case series of 15 MS patients receiving cladribine or alemtuzumab reported a CoV-2 IgG response in 100% (4 of 4) of cladribine-treated patients receiving the Pfizer vaccine, 43% (3 of 7) of cladribine patients receiving the Sinopharm (inactivated) vaccine, and 100% (4 of 4) in alemtuzumab-treated patients receiving either the Pfizer or Sinopharm vaccine (Drulovic et al. Mult Scler Relat Disord 2021;54:103150). The mean time to vaccination was 6 and 7 months, respectively, after the last dose of cladribine and alemtuzumab.

Finally, a case report found that two patients responded to the Pfizer or AstraZeneca vaccine when administered >3 months after the second treatment cycle of cladribine despite incomplete lymphocyte reconstitution. Two other patients were vaccinated while on ocrelizumab: one patient mounted an antibody response when vaccinated three months after the last infusion, whereas the second patient failed to mount a response when vaccinated two months after the last infusion (Buttari et al. Mult Scler Relat Disord 2021;52:102983).

Some authors have noted that the absence of a detectable antibody response does not necessarily mean an absence of immunity; T cell response and innate immunity are not routinely evaluated (Peterheit et al. Ther Adv Neurol Disord 2021;14:1-2). An interesting finding is that mRNA vaccines induce a broad CD4+ response, with T cell cross-recognition of the spike protein from coronaviruses (HCoV-229E, HCoV-NL63, HCoV-OC43) that cause the common cold (Bezawit et al. J Clin Invest 2021;131:e149335). This T cell response was also effective against the modified spike proteins of CoV-2 variants.

To date, only one case of vaccine failure has been reported in an MS patient receiving an anti-CD20 therapy. A 52-year-old male with MS received the Pfizer vaccine doses about two and five weeks after the last ocrelizumab infusion; he developed COVID-19 about 19 days after the second vaccination (Chilimuri et al. Vaccines (Basel) 2021;9:219). The same group recently reported a second vaccine failure in a 73-year-old patient without MS who was receiving rituximab (Chilimuri et al. Rheumatol Adv Pract 2021;5:rkab038).

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