ECTRIMS2021 cladribine vaccination

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So ECTRISM2021 starts today and over the next few weeks I may extract some abstracts. As a CladLad (as I have been working with it for some time since Merck dropped the ball in 2010 when it terminated its development, followed by resumption of interest in 2017, as we made it interesting), I thought I would start with some cladribine news.

If you remember we have shown that there is rapid repopulation of B cells after cladribine, suggesting that vaccination responses to COVID-19 and other vaccines should be OK. This fits with the RNA data that we showed previously

Up to 2021 infromation about this was pretty non-existant. However there now hundreds/thousands of cladribine treated indiviudals who are not vaccinated. At ECTRIMS 2021 there is more data on COVID19 vaccination and Flu Vaccination. In contrast to the poor response to anti-CD20 antibodies, in both cases there is a relatively good response as our work predicts.

P780 – Effect of cladribine on COVID-19 serology responses following 2 doses of the BNT162b2 mRNA vaccine in patients with multiple sclerosis

L. Brill1A. Rechtman1, O. Zveik1, N. Haham1, N. Levin1, A. Vaknin-Dembinsky1
1Hadassah-Medical Center, Ein–Kerem, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
Introduction: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system that usually requires long-term immunotherapy. Due to the immunosuppressive mechanisms of several disease modifying treatments, questions have been raised whether MS patients can be vaccinated, and will respond to the vaccine, as healthy controls. Cladribine is a purine antimetabolite indicated for the treatment of active forms of MS. To date, data on serological response of cladribine-treated patients is limited.
Aims: To assess antibody response to mRNA COVID-19 vaccine in MS patients, both untreated, or treated with Cladribine or interferon beta1a (IFNB1a). 
Methods: Study sample included adult patients with MS treated with cladribine (n=17), IFNB1a (n=16), or untreated (n=18), and healthy controls (HC, n=35). All participants received two doses of mRNA COVID-19 vaccine (Pfizer). Serology response to spike protein of COVID-19 was measured using Liaison SARS-CoV-2 S1/S2 IgG assay. A positive response is AU/mL greater than 19.
Results: All MS patients treated with cladribine (100%) had positive serology response against the spike protein (S1/S2) 2-3 weeks after vaccination as was measured in the HCs, untreated MS, and IFNB1a-treated patients (all had 100% response).  The median (IQR) of S1/S2 IgG antibodies postvaccination was 261.0(172.0) AU/mL in HCs, 303.5(233.5) in untreated MS, 254.0(222.0) in IFNB1a treated and 239.0(240.5) in cladribine treated patients. Also, we found no correlation between age, sex, EDSS, time from last cladribine dose, total cladribine dose, and specific COVID-19 IgG levels. 
Conclusion: We found no significant decrease in serology response in cladribine, INFB1a, and untreated MS patients compared to HCs. Knowing that anti-COVID19 antibodies are expressed in MS patients is reassuring and will help physicians to develop consensus guidelines regarding how to treat MS patients in the era of COVID-19 pandemic.

P649 – Humoral immune response to the influenza vaccine in multiple sclerosis patients treated with cladribine or rituximab

G.O. Nygaard1, S. Schikora-Rustad2, I.H. Lie1, A. Aase3, I.J. Leiknes2, M. König1, O. Hungnes3, Å. Mygland2,4,5, T. Berge6,7, L. Skattebøl1,8, J.-A. Zwart6, H.F. Harbo8,1, I.S Aaberge3, E.G. Celius1,8Å.R. Lorentzen2,9
1Oslo University Hospital, Departmend of Neurology, Oslo, Norway, 2Sørlandet Hospital, Department of Neurology, Kristiansand, Norway, 3Norwegian Institute of Public Health, Division of Infection Control and Environmental Health, Oslo, Norway, 4University of Bergen, Department of Clinical Medicine, Bergen, Norway, 5Sørlandet Hospital Trust, Department of Habilitation, Kristiansand, Norway, 6Oslo University Hospital, Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo, Norway, 7Oslo Metropolitan University, Department of Mechanical, Electronic and Chemical Engineering, Oslo, Norway, 8University of Oslo, Institute of Clinical Medicine, Oslo, Norway, 9Sørlandet Hospital, The Norwegian National Advizory Unit on Tick-Borne Diseases, Arendal, Norway
Introduction: The high-efficacy disease modifying treatments (DMTs) cladribine and off-label rituximab are used by persons with multiple sclerosis (MS) world-wide. A possible side effect of these DMTs could be a diminished humoral vaccine response. It is important for patients, clinicians and authorities to know whether vaccines offer protection for patients using these DMTs.
Aim: To characterize the humoral immune response to seasonal influenza vaccination in MS patients treated with high-efficacy DMTs.
Objective: The objective was to compare the development of specific antibodies (IgG) in response to the 2020/2021 tetravalent influenza vaccine between cladribine or rituximab treated MS patients and healthy controls (HCs).
Methods: MS patients treated with cladribine or rituximab and HC at Oslo University Hospital and Sørlandet Hospital, Norway, donated a blood sample 3 to 23 weeks after influenza vaccination. Only 12 cases of seasonal influenza was confirmed in the country during winter 2020/2021, indicating that all immune responses originated from vaccinations. Antibodies against influenza virus (B/Washington/02/2019) were measured by hemagglutination inhibition assay. Here we report on preliminary analyses of the proportion of patients and HC with antibody titers >20. In the final analyses we will report on proportion of patients with different titer levels and test whether there was an association between the antibody titer and Vitamin D, lymphocyte count, IgG level, time since treatment or vaccination. 
Results: Cladribine patients (n=33) were 40 years (range 21-67), 76% female, months of treatment 15 (range 1-30), while rituximab patients (n=61) were 46 years (range 22-73), 70% female, months  of treatment 20 (range 1-49) and HC (n=51)were 40 years (range 22-65), 75% female.  Preliminary results show that antibody titers >20 was detected in 91% treated with cladribine (30/33), 62% treated with rituximab (38/61) and 94 % of HC (48/51) (p<0.05 are considered significant, HC not significant vs cladribine, p<0.01 vs rituximab).
Conclusions: Preliminary results indicate that more than a third of patients treated with rituximab did not develop any humoral immune response, while patients treated with cladribine developed similar humoral immune responses as HC to influenza vaccination.

The interesting paper for cladribine is the “CLASSIC study” presented by ProfG. What happened to those people in the pre 2010 studies who were on oral cladribine when the trial works was terminated

COI:multiple

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

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MouseDoctor

6 comments

  • For cladribine, surely the study has to be split by weeks from taking the pills. The response may be great for people that are 6+ months but what about those that are just 2 months from treatment. Or ideally , regardless of time from treatment would a better measure be lymphocyte count – what is the response by different levels as different people take different amount of time to regain B cells.

    • Published Israeli data suggests good antibody responses occur regardless of lymphocyte counts or where in the treatment cycle the vaccine is given.

  • Thanks MD for insights from Ectrims we cannot access. Do you know if the authors of the second poster observed correlation between vitD and IgGs?

  • Come on MD1…..you can not tease us with…….”The interesting paper for cladribine is the CLASSIC study presented by ProfG. What happened to those people in the pre 2010 studies who were on oral cladribine when the trial works was terminated”

    You know pwms who read this blog are a resourceful bunch…..IMO, the preliminary results presented back in April 2021 looked relatively good.

    1) Any further update on the CLASSIC study going to be provided soon? 2) Since we are talking about cladribine, would be nice to get an update on Prof. K’s cladribine projects/data sets.

    https://medical.emdserono.com/content/dam/web/health-care/biopharma/web/USMI/congress-presentations/Cladribine-2-Giovannoni-G-et-al-CLASSIC-MS-Long-term-Efficacy-and-Real-World-Treatment-Phase-III-Parent.pdf

      • Sorry, Americans can be so impatient sometimes 🙂

        Cladribine is my third treatment in the same amount of years (adverse reactions to previous DMTs, not due to breakthrough activity per say), so I am just hopeful for some reassuring data.

        I look forward to reading your post!

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