Comparative Efficacy of Targeted Systemic Therapies for Moderate-to-Severe Atopic Dermatitis without Topical Corticosteroids: An Updated Network Meta-analysis.

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.

Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease.

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.

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.

Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids: Systematic Review and Network Meta-analysis.

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.

Abortion service provision in South Asia: A comparative study of four countries.

OBJECTIVES: Nationally representative evidence on abortion service provision is scarce in South Asia. To inform improvements in service provision, this paper assesses the availability of facility-based postabortion services in Nepal, India (six states), Bangladesh and Pakistan, and legal abortion services in India and Nepal and Bangladesh (where the official term used is menstrual regulation or MR). STUDY DESIGN: The paper presents comparable indicators on three aspects of abortion service provision from representative surveys of public and private sector facilities, conducted over 2012-2015. Indicators cover three areas: (a) need for abortion-related care (total number of abortions and percent of abortions that are legal and the postabortion treatment rate); (b) availability and accessibility of facility-based abortion-related services (percent of facilities offering only one of the two services, percent which are public and percent located in rural areas); (c) quality of facility-based abortion care (percent of legal abortions using procedures not recommended by WHO and percent of women turned away when seeking abortion or MR services). RESULTS: The proportion of all abortions that are illegal ranges from 58% to almost 78% in the three countries where abortion is permitted under broad criteria. The annual treatment rate for abortion complications ranges from about 4 to 26 per 1000 women ages 15-49 across the countries and states covered. In India and Nepal, less than 40% of public sector facilities that are permitted to provide abortion services do so; in Bangladesh, the situation is somewhat better, at 53% providing MR. Across the six Indian states, 4-43% of facilities that offer abortion care are located in rural areas, disproportionately lower than the proportion of women living in rural areas (49-87%). About 30-60% of facilities offered only postabortion care and did not offer legal services in the three countries where legal services are permitted (with the sole exception of Tamil Nadu where this proportion was only 11%); of the remaining facilities, the large majority offered both services. Medication abortion is offered by the large majority of facilities that provide induced abortion and accounts for 40-45%, of facility-based abortions in Nepal and four of the states of India; in Assam and Bihar, this proportion was much lower (13% and 27% respectively). Invasive procedures that are not recommended by WHO are more widely used in India (up to 25-37% of facility-based abortions are D&C procedures; the large majority of this group are D&C, and a small proportion may be D&E, a WHO-recommended abortion procedure, that could not be separated out in this study because providers use the two labels interchangeably); by comparison, the proportion is much smaller in Nepal (5%). Between 22% to a little over half of facilities turned away some women who would otherwise be eligible for an abortion or MR procedure in Nepal, the six Indian states, and Bangladesh. CONCLUSIONS: There is an urgent need to increase access to abortion, MR and postabortion services, especially for rural women. Greater access to legal abortion/MR services in the three countries that permit these procedures would increase the proportion of abortions that are legal and safe, reduce morbidity and the need for facility-based treatment for complications. Broadening the legal criteria under which abortion is permitted in Pakistan, and implementing access under such broader criteria, is needed to achieve the same improvements in Pakistan. Ensuring that these services are of high quality and comprehensive-meeting WHO-recommended standards-is essential to protect women's reproductive health and rights. IMPLICATIONS: To improve access to abortion, MR and postabortion care in South Asia, all facilities (public and private) permitted to provide these services should do so, and should include medication abortion. Improvements in quality of care are critical: invasive procedures (D&C) should be eliminated through adherence to WHO's standards of safe abortion care and women seeking abortions should not be turned away because of providers' biases.

Correction: Abortion in Zimbabwe: A national study of the incidence of induced abortion, unintended pregnancy and post-abortion care in 2016.

[This corrects the article DOI: 10.1371/journal.pone.0205239.].

Abortion in Zimbabwe: A national study of the incidence of induced abortion, unintended pregnancy and post-abortion care in 2016.

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.

Reasons why women have induced abortions: a synthesis of findings from 14 countries.

OBJECTIVE: Many reasons inform women's reproductive decision-making. This paper aims to present the reasons women give for obtaining induced abortions in 14 countries. STUDY DESIGN: We examined nationally representative data from 14 countries collected in official statistics, population-based surveys, and facility-based surveys of abortion patients. In each country, we calculated the percentage distribution of women who have abortions by main reason given for the abortion. We examined these reasons across countries and within countries by women's sociodemographic characteristics (age, marital status, educational attainment, and residence). Where data are available, we also studied the multiple reasons women give for having an abortion. RESULTS: In most countries, the most frequently cited reasons for having an abortion were socioeconomic concerns or limiting childbearing. With some exceptions, little variation existed in the reasons given by women's sociodemographic characteristics. Data from three countries where multiple reasons could be reported in the survey showed that women often have more than one reason for having an abortion. CONCLUSION: This study shows that women have abortions for a variety of reasons, and provides a broad picture of the circumstances that inform women's decisions to have abortions. IMPLICATIONS: Future research should examine in greater depth the personal, social, economic, and health factors that inform a woman's decision to have an abortion as these reasons may shed light on the potential consequences that unintended births can have on women's lives.

Correction: Characteristics of women obtaining induced abortions in selected low- and middle-income countries.

[This corrects the article DOI: 10.1371/journal.pone.0172976.].

Characteristics of women obtaining induced abortions in selected low- and middle-income countries.

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.

Abortion Incidence and Unintended Pregnancy in Nepal.

CONTEXT: Although abortion has been legal under broad criteria in Nepal since 2002, a significant proportion of women continue to obtain illegal, unsafe abortions, and no national estimates exist of the incidence of safe and unsafe abortions. METHODS: Data were collected in 2014 from a nationally representative sample of 386 facilities that provide legal abortions or postabortion care and a survey of 134 health professionals knowledgeable about abortion service provision. Facility caseloads and indirect estimation techniques were used to calculate the national and regional incidence of legal and illegal abortion. National and regional levels of abortion complications and unintended pregnancy were also estimated. RESULTS: In 2014, women in Nepal had 323,100 abortions, of which 137,000 were legal, and 63,200 women were treated for abortion complications. The abortion rate was 42 per 1,000 women aged 15-49, and the abortion ratio was 56 per 100 live births. The abortion rate in the Central region (59 per 1,000) was substantially higher than the national average. Overall, 50% of pregnancies were unintended, and the unintended pregnancy rate was 68 per 1,000 women of reproductive age. CONCLUSIONS: Despite legalization of abortion and expansion of services in Nepal, unsafe abortion is still common and exacts a heavy toll on women. Programs and policies to reduce rates of unintended pregnancy and unsafe abortion, increase access to high-quality contraceptive care and expand safe abortion services are warranted.