Severe skin reactions associated with cladribine in people with multiple sclerosis

Mateo-Casas, María; Reyes, Saúl; O'Toole, EA; Trane, Stefania De; Yıldız, Özlem; Allen-Philbey, Kimberley; Mathews, Joela; Baker, David; Giovannoni, Gavin; Schmierer, Klaus

doi:10.1016/j.msard.2020.102140

Cited by 6 publications

(8 citation statements)

References 17 publications

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“…As reported previously, 9,21 one patient suffered a myocardial infarction 6 weeks after starting Litak ® and three developed a severe allergic skin reaction (SASR) with complete resolution within weeks on steroids and antihistamines.…”

Section: Safety and Tolerabilitysupporting

confidence: 64%

“…Skin-related AEs, including shingles, were seen in 6%, including three previously reported cases of SASR. 21 A recent report on 239 pwMS treated with CladT detailed further skin reactions, and an overall incidence of 32%, 32 such that we conclude Litak ® does not harbour a higher risk of skin pathologies than the licenced oral compound or indeed other highly effective immunotherapies used in MS. 33 Other AEs were rare. Of note, headaches were uncommon.…”

Section: Discussionmentioning

confidence: 53%

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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: Safety and Tolerabilitysupporting

confidence: 64%

Section: Discussionmentioning

confidence: 53%

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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“…Dermatomal herpes infections and rare cases of skin rash are the only described (transient) skin-related AEs of cladribine so far. 2,3 Moreover, there has long been uncertainty whether cladribine treatment increases the risk of malignancy. 2,4…”

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confidence: 99%

Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment

Rolfes

Pfeuffer

Hackert

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo report 77 patients with multiple sclerosis (MS) who developed skin-related adverse events (AEs) following treatment with cladribine.MethodsWe evaluated our prospective bicentric cladribine cohort. Cladribine-treated patients with a skin AE were identified.ResultsTwo hundred thirty-nine cladribine-treated patients with MS were evaluated. Seventy-seven patients (32%) showed at least 1 skin AE at median 1 month after cladribine initiation (range: 1–12). Within first 3 months following last cladribine exposition, hair thinning (n = 28, 12%), skin rash (n = 20; 8%), mucositis (n = 13, 5%), and pruritus (n = 6, 3%) were observed. Furthermore, 35 patients (15%) developed herpes virus infections (time since last cladribine exposition: median 83 [range: 10–305]). In 15 patients, herpes zoster infection was severe (CTCAE grade ≥ 3) and required hospitalization. Delayed skin AEs (≥3 months after a cladribine treatment cycle) involved 1 case of leukocytoclastic vasculitis and 2 cases of alopecia areata. Finally, 2 patients presented with in total 3 isolated precancerous lesions (1 leukoplakia simplex and 2 actinic keratosis) and 1 patient developed a squamous cell carcinoma.ConclusionSkin AEs are common in patients with MS treated with cladribine. Until risk management plans have been adjusted to include these phenomena, clinicians should perform a thorough clinical follow-up and in suspicious cases seek early interdisciplinary support. In light of the observed delayed skin reactions, we further emphasize the necessity of careful clinical surveillance of cladribine-treated patients for yet undescribed secondary autoimmune events.Classification of EvidenceThis study provides Class IV evidence that skin-related AEs are frequent in patients with MS following cladribine in a real-world setting.

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“…However, a large prospective cohort study confirmed impaired effectiveness and safety of this therapeutic switch [37]. In contrast, cladribine remained effective and safe following fingolimod treatment [22], but-although no study yet examined the cumulative risk of adverse skin events-cladribine predisposes to dermatological side effects, including skin tumors [50,51], and thus concerns remain. Finally, natalizumab may remain an option but there is no real-world evidence yet that this switch is beneficial.…”

Section: Discussionmentioning

confidence: 99%

Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents

et al. 2022

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A critical issue in the management of relapsing MS (RMS) is the discontinuation of disease-modifying treatments (DMT) due to lack of efficacy, intolerability or impending risks. With new therapeutic agents introduced into the treatment of RMS, immediate- and long-term consequences of sequential drug use, as well as the effect of the sequence in which the drugs are given, are unclear but may affect efficacy, adverse events, and long-term immunocompetence. In the absence of clinical studies specifically addressing these concerns, observations from clinical practice are of particular value in guiding current management algorithms. Prompted by a study published by Ferraro et al. in this journal, we set out to provide an overview of the published real-world evidence on the effectiveness and safety of switching from fingolimod to another DMT in patients with active RMS. Seventeen publications reporting relevant information were identified. The literature suggests that immune cell depletion induced by alemtuzumab or ocrelizumab is associated with an increased risk of relapse and worsening disability in patients switching from fingolimod compared to patients switching from other therapeutic agents. However, the evidence reported for natalizumab and cladribine is inconclusive. While shortening of the washout period may limit early disease reactivation after fingolimod discontinuation, there is no strong evidence that the duration of the washout period or the absolute lymphocyte count at baseline are predictors of attenuated long-term efficacy. Further real-world studies are required to better understand outcomes among patients who are under-represented in controlled trials.

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Severe skin reactions associated with cladribine in people with multiple sclerosis

Cited by 6 publications

References 17 publications

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment

Neurological update: treatment escalation in multiple sclerosis patients refractory to fingolimod—potentials and risks of subsequent highly active agents

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