46 research outputs found
Efficacy and safety of ciclosporin versus methotrexate in the treatment of severe atopic dermatitis in children and young people (TREAT): a multicentre parallel group assessor-blinded clinical trial
Background
Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings.
Objectives
To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial.
Methods
We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2–16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg–1 daily) or MTX (0.4 mg kg–1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status.
Results
In total, 103 participants were randomized (May 2016–February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD –5.69, 97.5% confidence interval (CI) –10.81 to –0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23–5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13–0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42–6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE.
Conclusions
Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation
The British Association of Dermatologists' Biologic Interventions Register (BADBIR): design, methodology and objectives
Ciclosporin compared to prednisolone therapy for patients with pyoderma gangrenosum: cost-effectiveness analysis of the STOP GAP trial
Background
Pyoderma gangrenosum (PG) is a painful, ulcerating skin disease with poor evidence for management. Prednisolone and ciclosporin are the most commonly used treatments, although not previously compared within a randomised controlled trial (RCT)
Objectives
To compare the cost-effectiveness of ciclosporin and prednisolone-initiated treatment for patients with PG.
Methods
Quality-of-life (EuroQoL EQ-5D-3L) and resource data were collected as part of the STOP-GAP trial: a multicentre, parallel-group, observer-blind RCT. Within-trial analysis used bivariate regression of costs and QALYs, with multiple imputation of missing data, informing a probabilistic assessment of incremental treatment cost-effectiveness from a health service perspective.
Results
In the base case analysis, when compared with prednisolone, ciclosporin was cost-effective due to a reduction in costs (net cost: -£1160; 95%CI: (-2991 to 672) and improvement in quality of life (net QALYs: 0.055; 95%CI: 0.018 to 0.093). However, this finding appears driven by a minority of patients with large lesions (≥20cm2) (net cost: -£5310; 95%CI: -9729 to -891; net QALYs: 0.077; 95%CI: 0.004 to 0.151). The incremental cost-effectiveness of ciclosporin for the majority of patients with smaller lesions was £23,374/QALY although the estimate is imprecise: the probability of being cost-effective at a willingness to pay of £20,000/QALY was 43%.
Conclusions
Consistent with the clinical findings of the STOP-GAP trial, patients with small lesions should receive treatment guided by the side effect profiles of the drugs and patient preference - neither strategy is clearly a preferred use of NHS resources. However, ciclosporin-initiated treatment may be more cost-effective for patients with large lesions