Severe lymphopenia after subcutaneous cladribine in a patient with multiple sclerosis: To vaccinate or not?

Mateo-Casas, María; Reyes, Saúl; Trane, Stefania De; Edwards, Freya; Espasandin, M; Anjorin, Grace; Baker, David; Schmierer, Klaus; Giovannoni, Gavin

doi:10.1016/j.ensci.2020.100279

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…The second patient died from H1N1 influenza-associated pneumonia, as reported previously. 22 This 53-year-old woman had an EDSS of 8.5 and died 11 weeks after completing her first course of Litak ® . Of note, her TLC was within normal range (1.1 × 10 9 L −1 ) 4 weeks after completing the course, but was then admitted at the beginning of week 11 with pneumonia and grade 4 lymphopenia 22 ; she died shortly after.…”

Section: Resultsmentioning

confidence: 99%

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Allen-Philbey

Trane

Mao

et al. 2021

Ther Adv Neurol Disord

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Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data ( n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data ( n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.

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Section: Resultsmentioning

confidence: 99%

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Allen-Philbey

Trane

Mao

et al. 2021

Ther Adv Neurol Disord

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“…Disease duration from first symptoms until data cut-off was 11.0 years (median; IQR: 8.2, 15.5). The reasons why 21 pwMS received only one course of SClad were as follows: personal choice ( n = 6), difficulties travelling to our centre (1), haematopoietic stem cell transplantation (HSCT) (1), switch to fingolimod (1), planned pregnancy (2), death (1), 18 low TLC prior to planned second treatment course (2), intensive treatment unit (ITU) admission following surgery (1), non-specific health issues (1) and not yet due second treatment course at the cut-off date of our cohort (5). Thus, there were 236 pwMS for further analysis (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis

Allen-Philbey,

De Trane,

MacDougall

et al. 2023

Ther Adv Neurol Disord

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Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood. Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity. Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment. Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable). Results: Of n = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad. Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad.

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“…Of similar note, no studies were found in patients taking cladribine, though a recent fatal case of influenza A associated pneumonia within months of administering subcutaneous cladribine causing critical severe lymphopenia was reported [ 69 ]. This raises a question of how to carefully plan MS treatments in the context of not only the disease itself but also of the risk associated with seasonal flu infections and the necessity to administer appropriate vaccinations before the cladribine course is started.…”

Section: Vaccination Overview In the Context Of Multiple Sclerosismentioning

confidence: 99%

Current Immunological and Clinical Perspective on Vaccinations in Multiple Sclerosis Patients: Are They Safe after All?

Tsur

Zaher

Tsur

et al. 2021

IJMS

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Vaccines work by stimulating the immune system, and their immunogenicity is key in achieving protection against specific pathogens. Questions have been raised whether in Multiple Sclerosis (MS) patients they could induce disease exacerbation and whether vaccines could possibly act as a trigger in the onset of MS in susceptible populations. So far, no correlation has been found between the vaccinations against influenza, hepatitis B, tetanus, human papillomavirus, measles, mumps, rubella, varicella zoster, tuberculosis, yellow fever, or typhoid fever and the risk of MS. Further research is needed for the potential protective implications of the tetanus and Bacillus Calmette–Guerin vaccines in MS patients. Nowadays with the emerging coronavirus disease 2019 (COVID-19) and recent vaccinations approval and arrival, the risk-benefit in MS patients with regards to safety and efficacy of COVID-19 vaccination in those treated with immunosuppressive therapies is of paramount importance. In this manuscript, we demonstrate how different vaccine types could be related to the immunopathogenesis of MS and discuss the risks and benefits of different vaccinations in MS patients.

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Severe lymphopenia after subcutaneous cladribine in a patient with multiple sclerosis: To vaccinate or not?

Cited by 6 publications

References 11 publications

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis

Current Immunological and Clinical Perspective on Vaccinations in Multiple Sclerosis Patients: Are They Safe after All?

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