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Background: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety of baricitinib in patients with active SLE in a 52-week phase 3 study. Methods: In a multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study, SLE-BRAVE-I, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard of care. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on a modified intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT03616912. Findings: 760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n=252), baricitinib 2 mg (n=255), or placebo (n=253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1·57 [95% CI 1·09 to 2·27]; difference with placebo 10·8 [2·0 to 19·6]; p=0·016), but not baricitinib 2 mg (126 [50%]; 1·14 [0·79 to 1·65]; 3·9 [-4·9 to 12·6]; p=0·47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile. Interpretation: The primary endpoint in this study was met for the 4 mg baricitinib group. However, key secondary endpoints were not. No new safety signals were observed. [ABSTRACT FROM AUTHOR]

Background: Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) in a range of data sources with mixed conclusions. Objectives: We compared the incidence of IBD – ulcerative colitis (UC) and Crohn disease (CD) – in patients with a CISD vs. similar persons without a CISD. Methods: In this cohort study using nationwide, longitudinal, commercial insurance claims data from the USA, we identified adults and children who were seen by a dermatologist between 2004 and 2020, and diagnosed with either psoriasis, atopic dermatitis, alopecia areata, vitiligo or hidradenitis suppurativa. Comparator patients were identified through risk-set sampling; they were eligible if they were seen by a dermatologist at least twice and not diagnosed with a CISD. Patient follow-up lasted until either IBD diagnosis, death, disenrolment or end of data stream, whichever came first. IBD events, UC or CD, were identified via validated algorithms: hospitalization or diagnosis with endoscopic confirmation. Incidence rates were computed before and after adjustment via propensity-score decile stratification to account for IBD risk factors. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated to compare the incidence of IBD in CISD vs. non-CISD. Results: We identified patients with atopic dermatitis (n = 123 614), psoriasis (n = 83 049), alopecia areata (n = 18 135), vitiligo (n = 9003) or hidradenitis suppurativa (n = 6806), and comparator patients without a CISD (n = 2 376 120). During a median follow-up time of 718 days, and after applying propensity-score adjustment for IBD risk factors, we observed increased risk of both UC (HRUC 2·30, 95% CI 1·61-3·28) and CD (HRCD 2·70, 1·69-4·32) in patients with hidradenitis suppurativa, an increased risk of CD (HRCD 1·23, 1·03-1·46) but not UC (HRUC 1·01, 0·89-1·14) in psoriasis, and no increased risk of IBD in atopic dermatitis (HRUC 1·02, 0·92-1·12; HRCD 1·08, 0·94-1·23), alopecia areata (HRUC 1·18, 0·89-1·56; HRCD 1·26, 0·86-1·86) or vitiligo (HRUC 1·14, 0·77-1·68; HRCD 1·45, 0·87-2·41). Conclusions: IBD was increased in patients with hidradenitis suppurativa. CD alone was increased in patients with psoriasis. Neither UC nor CD was increased in patients with atopic dermatitis, alopecia areata or vitiligo. What is already known about this topic? Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) utilizing a range of data sources, with mixed conclusions. What does this study add? This large-scale, claims-based cohort study expands current knowledge by providing background rates for IBD across multiple CISDs using consistent methods and within a single, nationally representative patient population. We observed a relative increased risk of IBD in patients with hidradenitis suppurativa, but the overall incidence rate difference of IBD was generally low. Crohn disease alone was significantly increased in patients with psoriasis, and neither ulcerative colitis nor Crohn disease was increased in patients with atopic dermatitis, vitiligo or alopecia areata. [ABSTRACT FROM AUTHOR]