Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment

Abstract

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.

Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study

“…The most frequently reported AE was headache, which is in line with the findings from the clinical trial program (Cook et al, 2019;Giovannoni et al, 2010). A recent prospective bicentric cohort study reported skin reactions to be common after cladribine tablets (Rolfes et al, 2021). In our study, skin disorders including alopecia, acne, and dermatitis were reported in five patients (2.8%).…”

“…In the present study, patients initiating cladribine tablets for MS were characterized by a high female to male ratio in contrast to previous cohorts (Bose et al, 2021;Lizak et al, 2021;Pfeuffer et al, 2021;Rolfes et al, 2021). The reason for the relative paucity of male individuals especially among treatment naive patients in this cohort is unknown.…”

“…Real-world data on cladribine tablets is still limited to a few cohorts (Bose et al, 2021;Lizak et al, 2021;Möhn et al, 2019;Patti et al, 2020;Pfeuffer et al, 2021;Rolfes et al, 2021). In the pivotal phase III CLARITY trial, patients who had failed two or more previous DMTs were excluded (Giovannoni et al, 2010).…”

Subcutaneous cladribine to treat multiple sclerosis: experience in 208 patients

“…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.…”

Cladribine Tablets for Relapsing–Remitting Multiple Sclerosis: A Clinician’s Review

“…Skin reactions are listed in prescribing information as potential AEs during treatment with cladribine tablets [ 7 , 8 ]. Reports from clinical experience in two centers in Germany indicated that within 3 months following the last dose of cladribine tablets, hair thinning, skin rash, mucositis, and pruritus can be observed [ 100 ]. Case reports of three patients who developed severe rash 3–192 days after receiving subcutaneously administered cladribine have highlighted severe skin reactions as a rare, but important, potential AE during treatment.…”