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Observational Study
. 2024 Nov 18;191(6):988-999.
doi: 10.1093/bjd/ljae287.

A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register

Helen Alexander  1 , Rayka Malek  1 , David Prieto-Merino  1 , Elizaveta Gribaleva  1 , Manisha Baden  1 , Paula Beattie, Sara Brown, Tim Burton, Shona Cameron  1 , Bola Coker, Michael J Cork, Ross Hearn, John R Ingram, Alan D Irvine, Graham A Johnston, Alice Lambert, Mark Lunt, Irene Man, Louise Newell, Graham Ogg, Prakash Patel  1 , Mandy Wan, Richard B Warren, Richard Woolf, Zenas Z N Yiu, Nick Reynolds, Michael R Ardern-Jones, Carsten Flohr  1
Affiliations
Free article
Observational Study

A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register

Helen Alexander et al. Br J Dermatol. .
Free article

Abstract

Background: The main conventional systemic treatments for atopic dermatitis (AD) are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomized controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA.

Objectives: To compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD.

Methods: We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). The minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression analysis was used to compare the hazard ratios of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits.

Results: We included 488 patients (311 adults and 177 children/adolescents) on dupilumab (n = 282), MTX (n = 149) or CyA (n = 57). CyA and MTX were primarily used as the first-line treatment, while dupilumab was mainly a second-line systemic treatment as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared with MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared with MTX. In patients with severe disease the reduction in EASI, POEM and PP-NRS was even greater with CyA. The incidence rates of AEs were similar across groups (734, 654 and 594 per 10 000 person-month on CyA, dupilumab and MTX, respectively).

Conclusions: This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.

Plain language summary

Atopic dermatitis (AD) is a common skin disease which causes dry and itchy skin. AD affects around one in five children and one in 10 adults in the UK. The main conventional systemic treatments are with drugs called methotrexate (MTX) and ciclosporin (CyA). As well as these, dupilumab was the first novel systemic agent to enter routine clinical practice. However, there are no studies that have directly compared the effectiveness or safety of these treatments. This study aimed to compare the effectiveness and safety of CyA, dupilumab and MTX. We compared these treatments in adults and children with AD who were participating in the UK–Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness was assessed using the Eczema Area and Severity Index (EASI), and with patient-reported severity scores for itch and quality of life. Patients were treated for a minimum of 28 days and followed up for 12 months. Treatment safety was determined by patient-reported side-effects at follow-up visits. A total of 488 patients were assessed, including 282 patients on dupilumab, 149 on MTX and 57 on CyA. We found that the time taken for AD severity EASI scores to reduce by 50%, 75% and 90% was shorter for patients on dupilumab and CyA, compared with MTX. Improvements in itch and quality of life were greater for patients treated with dupilumab, compared with MTX. In patients with severe AD, improvement was even greater than with CyA. The incidence of side-effects was similar with dupilumab, CyA and MTX treatments. Overall, our findings suggest that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within 1 year of follow-up.

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Conflict of interest statement

Conflicts of interest The full conflicts of interest statement is provided in Appendix 3.

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