Dataset Information

Efficacy and Safety of Low-Dose Cyclosporine Relative to Immunomodulatory Drugs Used in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

ABSTRACT: Cyclosporine A (CsA) is effective in treating moderate-to-severe atopic dermatitis (AD). This systematic review and meta-analysis aimed to summarize the effectiveness and safety of low-dose (<4 mg/kg) versus high-dose (≥4 mg/kg) CsA and other systemic immunomodulatory agents in patients with AD. Five randomized controlled trials met the inclusion criteria. The meta-analysis included 159 patients with moderate-to-severe AD who were randomized to receive low-dose CsA, and 165 patients randomized to receive high-dose CsA and other systemic immunomodulatory agents. We found that low-dose CsA was not inferior to high-dose CsA and other systemic immunomodulatory agents in reducing AD symptoms [standard mean difference (SMD) -1.62, 95% confidence interval (CI) -6.47; 3.23]. High-dose CsA and other systemic immunomodulatory agents showed a significantly lower incidence of adverse events [incidence rate ratio (IRR) 0.72, 95% CI 0.56; 0.93], however, after sensitivity analysis, there was no difference between the two groups except for one study (IRR 0.76, 95% CI 0.54; 1.07). Regarding serious adverse events requiring discontinuation of treatment, we observed no significant differences between low-dose CsA and other systemic immunomodulatory agents (IRR 1.83, 95% CI 0.62; 5.41). Our study may justify the use of low-dose CsA rather than high-dose CsA and other systemic immunomodulatory agents in moderate-to-severe AD.

SUBMITTER: Kim K

PROVIDER: S-EPMC9959975 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Low-Dose Cyclosporine Relative to Immunomodulatory Drugs Used in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Kim Kyunghoon K Kim Mina M Rhee EunHee E Lee Mi-Hee MH Yang Hyeon-Jong HJ Park Suyeon S Kim Hwan Soo HS

Journal of clinical medicine 20230209 4

Cyclosporine A (CsA) is effective in treating moderate-to-severe atopic dermatitis (AD). This systematic review and meta-analysis aimed to summarize the effectiveness and safety of low-dose (<4 mg/kg) versus high-dose (≥4 mg/kg) CsA and other systemic immunomodulatory agents in patients with AD. Five randomized controlled trials met the inclusion criteria. The meta-analysis included 159 patients with moderate-to-severe AD who were randomized to receive low-dose CsA, and 165 patients randomized t ...[more]

PMID: 36835928

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Project description:Given the lack of head-to-head studies of systemic therapies in moderate-to-severe atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision-making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short-term (12-16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient-reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti-inflammatory therapy). RCTs were analysed in fixed-effects and random-effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI-50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI-75 and EASI-90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI-50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment-emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45-2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35-2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short-term RCTs.

Project description:Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

Project description:ImportanceThe dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD).ObjectiveTo assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment.Design, setting, and participantsThe Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator's Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016.InterventionsHigh-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks.Main outcomes and measuresPercentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety.ResultsAmong the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (-0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, -3.84%; dupilumab every 8 weeks, -6.84%; placebo, -21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively).Conclusions and relevanceIn this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment.Trial registrationClinicalTrials.gov identifier: NCT02395133.

Dataset Information

Efficacy and Safety of Low-Dose Cyclosporine Relative to Immunomodulatory Drugs Used in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

Publications

Efficacy and Safety of Low-Dose Cyclosporine Relative to Immunomodulatory Drugs Used in Atopic Dermatitis: A Systematic Review and Meta-Analysis.

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