Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis

Abstract

IntroductionCutaneous adverse events (AEs) have been observed in clinical studies of daclizumab high-yield process (HYP) in relapsing-remitting multiple sclerosis (RRMS). Here, we report cutaneous AEs observed in the randomized, double-blind, active-comparator DECIDE study (ClinicalTrials.gov identifier, NCT01064401).MethodsDECIDE was a randomized, double-blind, active-controlled phase 3 study of daclizumab HYP 150 mg subcutaneous every 4 weeks versus interferon (IFN) beta-1a 30 mcg intramuscular (IM) once weekly in RRMS. Treatment-emergent AEs were classified and recorded by investigators. Investigators also assessed the severity of each AE, and whether it met the criteria for a serious AE. Cutaneous AEs were defined as AEs coded to the Medical Dictionary for Regulatory Activities System Organ Class of skin and subcutaneous tissue disorders. The incidence, severity, onset, resolution, and management of AEs were analyzed by treatment group.ResultsCutaneous AEs were reported in 37% of daclizumab HYP-treated patients and 19% of IFN beta-1a-treated patients. The most common investigator-reported cutaneous AEs with daclizumab HYP were rash (7%) and eczema (4%). Most patients with cutaneous AEs remained on treatment (daclizumab HYP, 81%; IM IFN beta-1a, 90%) and had events that were mild or moderate (94% and 98%) and subsequently resolved (78% and 82%). Most patients with cutaneous AEs did not require treatment with corticosteroids or were treated with topical corticosteroids (daclizumab HYP, 73%; IM IFN beta-1a, 81%). Serious cutaneous AEs were reported in 14 (2%) daclizumab HYP patients and one (<1%) IM IFN beta-1a patient.ConclusionThere was an increased risk of cutaneous AEs with daclizumab HYP. While physicians should be aware of the potential for serious cutaneous AEs, the typical cutaneous AEs were mild-to-moderate in severity, manageable, and resolved over time.FundingBiogen and AbbVie Biotherapeutics Inc.Trial registrationClinicalTrials.gov identifier, NCT01064401.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0353-2) contains supplementary material, which is available to authorized users.

Treatment and disease management of multiple sclerosis patients

“…For treatment with natalizumab, specific thresholds of anti–JC virus antibody index are associated with different levels of PML risk (Tysabri, ) and may help patients better understand their individual risk of this serious safety signal (van Rossum et al., ). For daclizumab, it is possible to manage skin reactions with use of topical and/or systemic corticosteroids (Krueger et al., ; Zinbryta, ) and elevations of serum transaminases and/or bilirubin can be managed by temporarily/permanently discontinuing treatment (Zinbryta, ). In addition, the European Medicines Agency recommends that patients who have had liver injury should not use daclizumab, as one daclizumab patient died of fulminant liver failure during an observational study and four cases of serious liver injury have been reported (European Medicines Agency, ).…”

▼ Daclizumab for MS

“…Approximately 32% of daclizumab-treated patients had cutaneous reactions (2% serious) that included rash, eczema and allergic dermatitis and erythema 2,13. Skin reactions were more common with daclizumab than with interferon beta-1a (37% vs. 19%; serious 2% vs. <1%) and led to treatment discontinuation in 5% and 1% of patients, respectively 10,16. One case of Stevens–Johnson syndrome and two cases of drug reaction with eosinophilia and systemic symptoms (DRESS) were suspected 13.…”

Skin Lesions in a Daclizumab-treated Patient with Multiple Sclerosis

“…1 Recently, several reports have communicated a large spectrum of cutaneous adverse reactions observed in patients treated with daclizumab for multiple sclerosis. 2 Cutaneous adverse reactions induced by daclizumab high-yield process (DAC-HYP), recommended for multiple sclerosis, have been previously reported in 37% of patients, mainly represented by "rash and eczema". 2 Another open-label phase I study of DAC-HYP reported that 77% of the enrolled patients presented skin adverse reactions, described clinically as "severe rash of psoriasiform phenotype" but with no characteristic histological features.…”

“…Daclizumab is a humanized monoclonal antibody against the α-subunit (CD25) of the high-affinity interleukin (IL)-2 receptor, used for the treatment of relapsing-remitting multiple sclerosis, with a large spectrum of cutaneous adverse reactions. 1,2 Physicians should be aware of potential side effects induced by daclizumab in the treatment of patients with relapsing multiple sclerosis. We present the case of a middle-aged man treated with daclizumab for multiple sclerosis, who developed skin reactions difficult to evaluate.…”