Monitoring trough levels in cyclosporine for atopic dermatitis: A systematic review

Abstract

Background Cyclosporine is a useful immunosuppressive agent for achieving disease control in moderate to severe atopic dermatitis in children and adults. However, it carries the potential for nephrotoxicity. Monitoring of drug levels is performed in other patient groups, such as transplant recipients, but is not commonplace in the management of atopic dermatitis. Objectives To investigate levels of nephrotoxicity associated with cyclosporine use in atopic dermatitis and assess potential correlation with trough levels of cyclosporine. Methods An electronic search was conducted on MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials and cohort studies assessing the safety profile of cyclosporine compared to placebo or other atopic dermatitis treatments, in adult and pediatric atopic dermatitis patients from 1966 to May 2019. Studies that did not assess renal toxicity were excluded from analysis. Results Thirty‐eight trials were included for analysis, excluding 11 that did not assess renal toxicity. Descriptive statistical analysis only was performed, due to the high heterogeneity between study methodologies. Significant renal toxicity was seen in 0%‐9% of pediatric participants. Monitoring of trough cyclosporine levels was performed in only 10 of the studies, and their correlation to toxicity or disease activity was not explored. Conclusion There is limited evidence in atopic dermatitis regarding trough level monitoring of cyclosporine. Currently, the practice is not commonplace, particularly in pediatrics, and this is reflected in trial methodology. Monitoring may be useful in specific pediatric groups, such as those on multiple concurrent medications, patients with hepatic or renal dysfunction and non‐responders to therapy.

Identifying biomarkers of treatment response to ciclosporin in atopic dermatitis through multiomic predictive modelling: DERMATOMICS study protocol

“…In AD as well as other dermatological entities, therapeutic level monitoring is not performed routinely and the therapeutic range associated with control of the disease has not been well established. Therapeutic monitoring of CsA levels in the treatment of AD could be useful in monitoring the efficacy and toxicity of treatment, 15 but it would be advantageous to define a more precise monitoring strategy. Many biomarkers of different types (pharmacogenetic, biochemical, immunological, etc) have been suggested in association with the safety and pharmacokinetics of CsA and with treatment response in AD; however, few are used in clinical practice.…”

What’s new in atopic eczema? An analysis of systematic reviews published in 2019. Part 2: treatment

“…Blake and Murrell examined nephrotoxicity with ciclosporin use in AE, 13 including 38 studies (RCTs and cohort studies) in their SR. Limited evidence to support the assessment of ciclosporin trough levels in AE management was found, although its use in specific patient groups was suggested; for example, in renal/hepatic dysfunction, polypharmacy and nonresponders to therapy. Meta‐analyses were not performed because of significant heterogeneity between studies.…”

Cyclosporine-Induced Posterior Reversible Encephalopathy Syndrome: An Adverse Effect in a Patient With Atopic Dermatitis

“…In contrast, severe adverse effects are uncommon with the lower doses of cyclosporine used for cutaneous conditions, and monitoring serum drug levels is not routinely practiced. 4 A 58-year-old man was referred to clinic with severe atopic dermatitis refractory to maximal topical therapy prescribed by an outside physician. He was started on cyclosporine as an anticipated bridge to dupilumab biologic therapy.…”