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Introduction: The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD. Methods: Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. Results: The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. Conclusions: Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient's personalized treatment plan. [ABSTRACT FROM AUTHOR]

Introduction: Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase 3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355). Methods: Matching-adjusted indirect comparison was conducted using individual patient-level data from RZB trials and published aggregated data from UST trials. During induction, patients received RZB 600 mg intravenous (IV) at weeks 0, 4, and 8 or a single dose of UST 6 mg/kg IV at week 0. During maintenance, patients received RZB 180 or 360 mg subcutaneous (SC) or UST 90 mg SC every 8 or 12 weeks to 52 weeks. Outcomes included proportion of patients achieving Crohn's Disease Activity Index (CDAI) response (decrease of ≥ 100 points or total score < 150) or remission (CDAI ≤ 150) and endoscopic improvement (measured by the Simple Endoscopic Score in CD [SES-CD]; response, ≥ 50% reduction from baseline; remission, SES-CD ≤ 2) following induction/baseline. Results: Higher proportions of patients achieved clinical and endoscopic outcomes with RZB vs. UST induction treatment, resulting in significantly (p ≤ 0.05) greater percent differences (95% confidence intervals) between groups for CDAI remission (15% [5%, 25%]) and endoscopic response (26% [13%, 40%]) and remission (9% [0%, 19%]). Following maintenance, rates of CDAI remission were similar (range − 0.3% to − 5.0%) for RZB vs. UST. Differences for endoscopic response and remission ranged from 9.3% to 27.7% and 11.6% to 12.5%, respectively; differences were significant (p < 0.05) for endoscopic response for both doses of RZB compared to UST 12-week dosing. Conclusions: This indirect comparison demonstrated higher rates of clinical and endoscopic outcomes during induction for RZB compared to UST; CDAI remission following maintenance was comparable. Direct comparisons of RZB and UST are warranted to validate these findings. Plain Language Summary: Using individual patient-level data from risankizumab and aggregated data from ustekinumab phase 3 Crohn's disease trials, we indirectly compared efficacy of risankizumab and ustekinumab to determine whether rates of improvement in disease symptoms (clinical) and endoscopic outcomes differed between treatments. Findings showed that clinical and endoscopic outcomes were more frequently achieved for patients receiving risankizumab versus ustekinumab after induction, while most maintenance outcomes were comparable. [ABSTRACT FROM AUTHOR]

Introduction/Background Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and Measure Up 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-tohead trial against dupilumab 300mg. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated stringent and composite measures of efficacy. Objectives: To indirectly compare upadacitinib and dupilumab on stringent and composite measures of skin clearance and itch resolution. Methods: A population-adjusted indirect comparison using covariate adjustment as a treatment effect calibration was conducted using individual patient data from Measure Up 1 and 2 and Heads Up. Specifically, the indirect comparison model estimated how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates (age, gender, race, country, previous use of systemic therapy, disease duration, baseline validated Investigator Global Assessment scale for AD score, and baseline Eczema Area and Severity Index [EASI]). Absolute response rates at weeks 4 and 16 were estimated for the following outcomes: no/minimal itch (Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1), 100% improvement in EASI (EASI 100), achievement of both =90% improvement in EASI (EASI 90) and WP-NRS 0/1, and achievement of both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to-treat population for the clinical trials, and utilized non-responder imputation. Results: Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg, and then dupilumab. This pattern was observed at week 4 on the achievement of WP-NRS 0/1 (upadacitinib 30 mg: 34.2% | upadacitinib 15 mg: 18.2% | dupilumab: 7.9%), EASI 100 (8.5% | 4.7% | 1.8%), EASI 90 & WP-NRS 0/1 (21.9% | 10.6% | 3.3%), and EASI 100 & WP-NRS 0/1 (6.4% | 3.5% | 1.2%). This ranking was maintained at week 16 for WP-NRS 0/1 (35.4% | 22.5% | 16.2%), EASI 100 (28.4% | 22.2% | 7.9%), EASI 90 & WP-NRS 0/1 (32.2% | 19.6% | 12.4%), and EASI 100 & WP-NRS 0/1 (19.6% | 12.7% | 4.2%). Conclusions: For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining stringent and composite outcomes after 4 and 16 weeks, followed by upadacitinib 15 mg, and then dupilumab. [ABSTRACT FROM AUTHOR]

Introduction Network meta-analysis (NMA) provides useful information for medical decision makers via comprehensive indirect comparisons across therapies. As the targeted systemic therapy options for moderate-to-severe atopic dermatitis (AD) continue to grow, it is critical to update NMAs as well. Objectives: To assess the comparative efficacy of targeted systemic therapies with concomitant topical corticosteroids (TCS) in moderate-to-severe AD by including the latest Phase 3 combination therapy data for abrocitinib, lebrikizumab, and dupilumab in the NMA presented in Thyssen et al, 2021. Methods: Data from the Phase 3 combination therapy trial for lebrikizumab in moderate-to-severe AD (ADhere [NCT04250337]) as well as an additional abrocitinib-dupilumab head-to-head Phase 3 trial (JADE DARE [NCT04345367]) were included in the analyses along with other eligible trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systematic literature review in Thyssen et al., 2021. Outcomes included ≥90% and ≥75% improvement in Eczema Area and Severity Index (EASI 90, EASI 75) from baseline, ≥4-point improvement in Pruritus Numerical Rating Scale from baseline (ΔNRS ≥4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with a ≥2-point reduction from baseline (IGA 0/1), at the week 16 timepoint of each study. Bayesian NMA was performed with fixed and random effects models, with and without baseline risk-adjustment; fit statistics were assessed. Inconsistency was assessed via unrelated mean relative effects models. Odds ratio (OR), number needed to treat (NNT), placebo-unadjusted absolute response rate (ARR), and Surface Under the Cumulative RAnking curve (SUCRA) scores were estimated. Statistical significance was assessed by OR 95% credible intervals excluding 1. Results: The updated NMA analyzed 8 unique placebo-controlled trials and 1 active-controlled trial involving 4391 patients in 23 arms across 6 targeted therapies. Fit statistics supported fixed effects models across outcomes. All therapies were statistically more efficacious than placebo across all outcomes except baricitinib 2 mg for EASI-90. For EASI-90, upadacitinib 30 mg had the most favorable response estimates (ARR=63.2%, OR=11.3, NNT=2.0, SUCRA=98.3%), followed by abrocitinib 200 mg (ARR=55.8%, OR=8.3, NNT=2.4, SUCRA=90.0%), dupilumab 300 mg (ARR=44.8%, OR=5.3, NNT=3.2, SUCRA=68.3%), abrocitinib 100 mg (ARR=44.0%, OR=5.2, NNT=3.3, SUCRA=65.8%), upadacitinib 15 mg (ARR=42.9%, OR=4.9, NNT=3.4, SUCRA=64.3%), and the newly added lebrikizumab 250 mg (ARR=28.9%, OR=2.7, NNT=6.6, SUCRA=39.9%). The rank order for EASI-75 was similar (upadacitinib 30 mg [ARR=78.3%, OR=9.5, NNT=2.0, SUCRA=98.5%], abrocitinib 200 mg [ARR=73.0%, OR=7.1, NNT=2.3, SUCRA=89.1%], upadacitinib 15 mg [ARR=66.1%, OR=5.1, NNT=2.7, SUCRA=71.0%], dupilumab 300 mg [ARR=65.3%, OR=5.0, NNT=2.7, SUCRA=69.2%], abrocitinib 100 mg [ARR=60.3%, OR=4.0, NNT=3.2, SUCRA=54.0%], and lebrikizumab 250 mg [ARR=54.5%, OR=3.1, NNT=3.8, SUCRA=41.2%]). For ΔNRS ≥4, upadacitinib 30 mg had the most favorable response (ARR=68.9%, OR=10.0, NNT=2.1, SUCRA=99.9%), followed by upadacitinib 15 mg (ARR=56.6%, OR=5.9, NNT=2.7, SUCRA=84.0%), abrocitinib 200 mg (ARR=51.6%, OR=4.8, NNT=3.1, SUCRA=75.6%), dupilumab 300 mg (ARR=49.3%, OR=4.4, NNT=3.3, SUCRA=67.0%), baricitinib 4 mg (ARR=44.4%, OR=3.6, NNT=4.0, SUCRA=57.7%), and abrocitinib 100 mg (ARR=35.9%, OR=2.5, NNT=5.9, SUCRA=36.1%); lebrikizumab 250 mg ranked eighth (ARR=33.4%, OR=2.3, NNT=7.0, SUCRA=31.3%). For IGA 0/1, upadacitinib 30 mg (ARR=66.5%, OR=11.7, NNT=2.0, SUCRA=99.6%) had the most favorable estimates, followed by abrocitinib 200 mg (ARR=53.5%, OR=6.8, NNT=2.6, SUCRA=86.6%), upadacitinib 15 mg (ARR=48.0%, OR=5.4, NNT=3.0, SUCRA=76.2%), dupilumab 300 mg (ARR=42.1%, OR=4.3, NNT=3.7, SUCRA=64.7%), abrocitinib 100 mg (ARR=39.1%, OR=3.8, NNT=4.1, SUCRA=56.1%), and baricitinib 4 mg (ARR=30.6%, OR=2.6, NNT=6.4, SUCRA=39.9%); lebrikizumab 250 mg ranked seventh (ARR=29.2%, OR=2.4, NNT=7.0, SUCRA=35.8%). Baricitinib 2 mg and tralokinumab 300 mg were generally ranked lower across outcomes. Conclusions: Among targeted therapies for moderate-to-severe AD used with concomitant TCS for 16 weeks, upadacitinib 30 mg remained the most efficacious therapy in this NMA, generally followed by abrocitinib 200 mg, upadacitinib 15 mg or dupilumab 300 mg, abrocitinib 100 mg, and baricitinib 4 mg or lebrikizumab 250 mg. [ABSTRACT FROM AUTHOR]

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD. Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis. Results: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily. Discussion: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment. Conclusion: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. [ABSTRACT FROM AUTHOR]

The landscape of targeted systemic treatments for moderate-to-severe atopic dermatitis (AD) continues to expand. With limited head-to-head randomized controlled trials conducted in AD, a network meta-analysis (NMA) helps inform treatment decisions by providing indirect comparisons across therapies. This study aims to update an NMA presented in Silverberg et al. (2022), assessing the comparative efficacy of targeted systemic treatments without concomitant topical corticosteroids in moderate-to-severe AD by including the latest Phase 3 monotherapy data for lebrikizumab. Data from the two most recently published Phase 3 monotherapy trials for lebrikizumab in moderate-to-severe AD [ADvocate1 (NCT04146363); ADvocate2 (NCT04178967)] were included in the analyses along with other eligible Phase 3 or 4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib identified through a systemic literature review in Silverberg et al. (2022). Prespecified efficacy outcomes included ≥90% and ≥75% improvement in Eczema Area and Severity Index (EASI 90, EASI 75) from baseline, ≥4-point improvement in Pruritus Numerical Rating Scale from baseline (ΔNRS ≥4) and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) with a ≥2-point reduction from baseline (IGA 0/1), at the primary endpoint timepoint for each study (Week 12 for abrocitinib, Week 16 for all other therapies). Bayesian NMA was performed with fixed-effect, random-effect and baseline risk-adjusted models; fit statistics and diagnostics were assessed. The odds ratio (OR), number needed to treat (NNT), placebo-unadjusted absolute response rate (ARR) and Surface Under the Cumulative RAnking curve (SUCRA) scores were estimated. Statistical significance was assessed by OR 95% credible intervals excluding 1. The updated NMA analysed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across six targeted therapies. Fit statistics and diagnostics supported fixed-effect models for all outcomes analysed. All targeted therapies had significantly greater response rates compared with placebo across all outcomes. For EASI 90, upadacitinib 30 mg had the most favorable response estimates (ARR = 58.3%, OR = 23.1, NNT = 1.9, SUCRA = 98.5%), followed by abrocitinib 200 mg (ARR = 45.2%, OR = 13.5, NNT = 2.5, SUCRA = 84.3%), upadacitinib 15 mg (ARR = 43.7%, OR = 12.8, NNT = 2.6, SUCRA = 82.0%), dupilumab 300 mg (ARR = 27.3%, OR = 6.2, NNT = 4.7, SUCRA = 52.8%), abrocitinib 100 mg (ARR = 26.8%, OR = 6.0, NNT = 4.8, SUCRA = 48.4%), baricitinib 4 mg (ARR = 25.0%, OR = 5.5, NNT = 5.2, SUCRA = 45.5%) and lebrikizumab 250 mg (ARR = 23.6%, OR = 5.1, NNT = 5.6, SUCRA = 40.0%). A similar rank order was observed for EASI 75 [upadacitinib 30 mg (ARR = 72.3%, OR = 19.1, NNT = 1.7, SUCRA = 98.5%), abrocitinib 200 mg (ARR = 64.6%, OR = 13.3, NNT = 1.9, SUCRA = 87.3%), upadacitinib 15 mg (ARR = 59.8%, OR = 10.9, NNT = 2.1, SUCRA = 80.2%), dupilumab 300 mg (ARR = 45.3%, OR = 6.0, NNT = 3.0, SUCRA = 55.4%), abrocitinib 100 mg (ARR = 44.9%, OR = 5.9, NNT = 3.1, SUCRA = 53.5%) and lebrikizumab 250 mg (ARR = 44.7%, OR = 5.9, NNT = 3.1, SUCRA = 53.9%)]. For ΔNRS ≥4, upadacitinib 30 mg also had the most favorable response (ARR = 56.1%, OR = 12.9, NNT = 2.1, SUCRA = 99.0%), followed by abrocitinib 200 mg (ARR = 45.4%, OR = 8.3, NNT = 2.8, SUCRA = 83.6%), upadacitinib 15 mg (ARR = 42.9%, OR = 7.6, NNT = 3.0, SUCRA = 79.2%), dupilumab 300 mg (ARR = 33.9%, OR = 5.2, NNT = 4.0, SUCRA = 54.2%), lebrikizumab 250 mg (ARR = 33.9%, OR = 5.1, NNT = 4.1, SUCRA = 54.1%) and abrocitinib 100 mg (ARR = 31.5%, OR = 4.6, NNT = 4.5, SUCRA = 46.1%). For IGA 0/1, upadacitinib 30 mg (ARR = 61.8%, OR = 19.4, NNT = 1.9, SUCRA = 99.9%) and upadacitinib 15 mg (ARR = 48.1%, OR = 11.1, NNT = 2.5, SUCRA = 86.9%) had the most favorable estimates, followed by abrocitinib 200 mg (ARR = 39.3%, OR = 7.7, NNT = 3.2, SUCRA = 75.5%), dupilumab 300 mg (ARR = 32.4%, OR = 5.7, NNT = 4.1, SUCRA = 62.1%) and lebrikizumab 250 mg (ARR = 28.0%, OR = 4.7, NNT = 5.0, SUCRA = 49.1%). Baricitinib 2 mg and tralokinumab 300 mg were generally ranked lower across outcomes. Among targeted treatments for moderate-to-severe AD used without concomitant topical corticosteroids for 12–16 weeks, upadacitinib 30 mg remains the most efficacious therapy in this NMA, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg and lebrikizumab 250 mg or abrocitinib 100 mg. [ABSTRACT FROM AUTHOR]

Background: Zimbabwe has the highest contraceptive prevalence rate in sub-Saharan Africa, but also one of the highest maternal mortality ratios in the world. Little is known, however, about the incidence of abortion and post-abortion care (PAC) in Zimbabwe. Access to legal abortion is rare, and limited to circumstances of rape, incest, fetal impairment, or to save the woman’s life. Objectives: This paper estimates a) the national provision of PAC, b) the first-ever national incidence of induced abortion in Zimbabwe, and c) the proportion of pregnancies that are unintended. Methods: We use the Abortion Incidence Complications Method (AICM), which indirectly estimates the incidence of induced abortion by obtaining a national estimate of PAC cases, and then estimates what proportion of all induced abortions in the country would result in women receiving PAC. Three national surveys were conducted in 2016: a census of health facilities with PAC capacity (n = 227), a prospective survey of women seeking abortion-related care in a nationally-representative sample of those facilities (n = 127 facilities), and a purposive sample of experts knowledgeable about abortion in Zimbabwe (n = 118). The estimate of induced abortion, along with census and Demographic Health Survey data was used to estimate unintended pregnancy. Results: There were an estimated 25,245 PAC patients treated in Zimbabwe in 2016, but there were critical gaps in their care, including stock-outs of essential PAC medicines at half of facilities. Approximately 66,847 induced abortions (uncertainty interval (UI): 54,000–86,171) occurred in Zimbabwe in 2016, which translates to a national rate of 17.8 (UI: 14.4–22.9) abortions per 1,000 women 15–49. Overall, 40% of pregnancies were unintended in 2016, and one-quarter of all unintended pregnancies ended in abortion. Conclusion: Zimbabwe has one of the lowest abortion rates in sub-Saharan Africa, likely due to high rates of contraceptive use. There are gaps in the health care system affecting the provision of quality PAC, potentially due to the prolonged economic crisis. These findings can inform and improve policies and programs addressing unsafe abortion and PAC in Zimbabwe. [ABSTRACT FROM AUTHOR]

Background: In 2010–2014, approximately 86% of abortions took place in low- and middle-income countries (LMICs). Although abortion incidence varies minimally across geographical regions, it varies widely by subregion and within countries by subgroups of women. Differential abortion levels stem from variation in the level of unintended pregnancies and in the likelihood that women with unintended pregnancies obtain abortions. Objectives: To examine the characteristics of women obtaining induced abortions in LMICs. Methods: We use data from official statistics, population-based surveys, and abortion patient surveys to examine variation in the percentage distribution of abortions and abortion rates by age at abortion, marital status, parity, wealth, education, and residence. We analyze data from five countries in Africa, 13 in Asia, eight in Europe, and two in Latin America and the Caribbean (LAC). Results: Women across all sociodemographic subgroups obtain abortions. In most countries, women aged 20–29 obtained the highest proportion of abortions, and while adolescents obtained a substantial fraction of abortions, they do not make up a disproportionate share. Region-specific patterns were observed in the distribution of abortions by parity. In many countries, a higher fraction of abortions occurred among women of high socioeconomic status, as measured by wealth status, educational attainment, and urban residence. Due to limited data on marital status, it is unknown whether married or unmarried women make up a larger share of abortions. Conclusions: These findings help to identify subgroups of women with disproportionate levels of abortion, and can inform policies and programs to reduce the incidence of unintended pregnancies; and in LMICs that have restrictive abortion laws, these findings can also inform policies to minimize the consequences of unsafe abortion and motivate liberalization of abortion laws. Program planners, policymakers, and advocates can use this information to improve access to safe abortion services, postabortion care, and contraceptive services. [ABSTRACT FROM AUTHOR]