Explore the vast range of titles available.

Background In previous clinical trials, patients with active rheumatoid arthritis (RA) treated with upadacitinib (UPA) have improved patient-reported outcomes (PROs). This post hoc analysis of SELECT-CHOICE, a phase 3 clinical trial, evaluated the impact of UPA vs abatacept (ABA) with background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on PROs in patients with RA with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR). Methods Patients in SELECT-CHOICE received UPA (oral 15 mg/day) or ABA (intravenous). PROs evaluated included Patient Global Assessment of Disease Activity (PtGA) by visual analog scale (VAS), patient’s assessment of pain by VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), morning stiffness duration and severity, 36-Item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Impairment (WPAI), and EQ-5D 5-Level (EQ-5D-5L) index score. Least squares mean (LSM) changes from baseline to weeks 12 and 24 were based on an analysis of covariance model. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) were compared using chi-square tests. Results Data from 612 patients were analyzed (UPA, n =303; ABA, n =309). Mean age was 56 years and mean disease duration was 12 years. One-third received ≥2 prior bDMARDs and 72% received concomitant methotrexate at baseline. At week 12, UPA- vs ABA-treated patients had significantly greater improvements in PtGA, pain, HAQ-DI, morning stiffness severity, EQ-5D-5L, 2/4 WPAI domains, and 3/8 SF-36 domains and Physical Component Summary (PCS) scores ( P <0.05); significant differences persisted at week 24 for HAQ-DI, morning stiffness severity, SF-36 PCS and bodily pain domain, and WPAI activity impairment domain. At week 12, significantly more UPA- vs ABA-treated patients reported improvements ≥MCID in HAQ-DI (74% vs 64%) and SF-36 PCS (79% vs 66%) and 4/8 domain scores ( P <0.05). Conclusions At week 12, UPA vs ABA treatment elicited greater improvements in key domains of physical functioning, pain, and general health and earlier improvements in HAQ-DI. Overall, more UPA- vs ABA-treated patients achieved ≥MCID in most PROs at all timepoints; however, not all differences were statistically significant. These data, however, highlight the faster response to UPA treatment. Trial registration NCT03086343 , March 22, 2017.

Universities are expected to strive for excellence but also for gender balance. Narrow interpretations of excellence in universities hinder women’s advancement in academia. In this paper, we ask if there are ways that these policies may be reconciled. Excellence is an “empty signifier” that must be filled with meaning. We have investigated how Heads of Departments enact “excellence” and gender balance in hiring processes in four Norwegian universities. Many HoD argued for broadening excellence criteria and framed excellence as a collective rather than an individual concern. This allows for reconciling top-down institutional demands for excellence and diversity while catering to local needs. Thus, our paper suggests that in a context where increased diversity among faculty is called for, this may open up a space for critical reflection about the criteria for assessing academic quality.

BackgroundUpadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). JAK inhibitors have been associated with an increased risk of herpes zoster (HZ) in patients with RA.ObjectivesTo evaluate the incidence and risk factors for HZ in UPA-treated patients with RA from the UPA phase III clinical trial programme.MethodsExposure-adjusted incidence/event rates for HZ were determined in patients receiving UPA (monotherapy or combination therapy) in six randomised phase III trials (data cut-off on 30 June 2020). HZ incidence and event rates were also determined in patients receiving methotrexate (MTX) monotherapy or adalimumab (ADA) + MTX. Multivariable Cox regression analysis was used to identify HZ risk factors in UPA-treated patients.ResultsA total of 5306 patients were included in this analysis. The incidence rate of HZ/100 patient-years (95% CI) was 0.8 (0.3 to 1.9), 1.1 (0.5 to 1.9), 3.0 (2.6 to 3.5) and 5.3 (4.5 to 6.2), in the MTX monotherapy, ADA + MTX, UPA 15 mg and UPA 30 mg groups, respectively. The majority of HZ cases with UPA (71%) involved a single dermatome. Prior history of HZ and Asian region were HZ risk factors in UPA-treated patients.ConclusionIn the UPA phase III RA clinical programme, HZ incidence and event rates were higher with UPA versus ADA + MTX or MTX monotherapy, and higher with the 30 mg versus 15 mg dose. Patients from Asia and those with a history of HZ may be at increased risk of HZ while receiving UPA.

Technologies called infrastructures are often considered to be inherently and opaquely political, but how they exert their politics has been both empirically and conceptually debated. Infrastructure studies have largely focused on (in)visibility or ‘infra’ qualities as central criteria for assessing who and what is included and excluded, and when. In this paper we argue that this binary is unproductive and propose the concept of interstructure to highlight the connective and aesthetic qualities of technologies as well as their political features. These features may be quite transparent but also ambivalent, which we demonstrate by analysing an elevator for cyclists in Belgrade, Serbia. We draw on material semiotics to unpack the practices, the sense-making and the political work of this elevator in relation to its design and use. The analysis is based on interviews and an observation study. It shows that the elevator elicited substantial articulation work among most users as well as the operators who ran it. The elevator’s politics were produced through continuous negotiations among actors with partial views. Unpredictable connections captured a clearly ambivalent politics. We conclude by arguing that similar political dynamics may be present in transport and urban technologies more generally and that the concept of interstructure offers a fruitful avenue to study them and their politics. 被称为基础设施的技术通常被认为具有内在的和不透明的政治性，但是，关于它们如何发挥它们的政治作用，却一直存在实证和概念上的争论。一直以来，基础设施研究主要专注在它的（不）可见或“基础”性质，将这些作为评估何时、将哪些人、哪些内容包括在内或排除在外的核心标准。在本文中，我们认为这种二分法是无效的，并提出了中间设施(interstructure) 的概念，以突出技术的连接性和美观性特征，以及它们的政治特征。这些特征可能很明显，但也很矛盾，我们通过分析塞尔维亚贝尔格莱德的一部自行车电梯来证明这一点。我们利用物质符号学来解释电梯的设计和使用中的行为、意义创造和政治工作。分析基于访谈和观察研究。分析表明电梯在大多数用户和操作者中引发了大量的衔接工作。这部电梯的政治是通过持不同观点的行为者之间不断的谈判而产生的。不可预测的联系捕获了一个明显矛盾的政治。我们的结论是，类似的政治动态可能存在于更广泛的交通和城市技术中，而中间设施的概念为研究它们和它们的政治提供了一个富有成效的途径。

ObjectivesMethotrexate is considered to be first-line therapy for rheumatoid arthritis (RA). However, a substantial proportion of treated patients do not achieve the desired goals of therapy. This analysis aimed to identify predictors of insufficient response to methotrexate in patients with early RA.MethodsThe Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab (OPTIMA) and PREMIER studies in patients with RA for <1 and <3 years, respectively, examined the efficacy of methotrexate and adalimumab in methotrexate-naive patients. This post hoc analysis included patients for whom initial methotrexate monotherapy was not successful after 6 months. Candidate predictors of insufficient response and clinically relevant radiographic progression (CRRP) included demographics, baseline disease characteristics and time-averaged disease variables over a 12-week interval. In OPTIMA, adalimumab was added to therapy after insufficient treatment response; in PREMIER, initial methotrexate therapy was continued; clinical, functional and radiologic outcomes were assessed after 1 year.ResultsBaseline 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) and time-averaged DAS28(CRP) over 4, 8 and 12 weeks were the strongest predictors of insufficient response to methotrexate and CRRP. Addition of adalimumab to methotrexate therapy was associated with better clinical, functional and radiographic outcomes after 1 year compared with continuing on methotrexate monotherapy.ConclusionsIn patients with early RA, baseline disease characteristics and early disease activity can predict response to methotrexate treatment and radiographic progression at 6 months. The addition of adalimumab at 6 months after methotrexate failure is associated with improved outcomes. These results support treatment-to-target strategies and timely adaptation of therapy in patients with early RA.Trial registration number NCT00420927, NCT00195663; Post-results.

What are the Seven Deadly Sins? Are they still acknowledged breaches of morality and ethical norms in our Western societies in the Third Millennium? The Seven Deadly Sins present an ethical catalog, a moral mirror for princes and rulers that originates in Catholic Christianity. This little book, however, is not primarily about religion, on the contrary: It respects the Greek origins of Western thought that have survived beyond Christian faith, praises the scientific achievements of the Enlightenment, and looks at our contemporary world with critical eyes. It is a unique blend of scientific analysis, analysis of Western contemporary culture and, lastly, satire. The authors, a group of friends living in Europe, present diverse views on a wide range of topics. Their principal intention is to open a debate about ethics, science, scepticism, and hypocrisy. A thought-provoking and inspiring read—about the present as well as the future.

In the phase 3 double-blind SELECT-CHOICE study of patients (pts) with prior inadequate response (IR) or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs), upadacitinib (UPA) showed superiority to abatacept (ABA) in change from baseline in 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and in the proportion of pts achieving DAS28(CRP) <2.6 at Week 12. To describe clinical responses in pts receiving UPA or ABA by number and mechanism of action of prior bDMARDs. 612 pts were randomized to once-daily UPA 15 mg or monthly intravenous ABA (<60 kg, 500 mg; 60–100 kg, 750 mg; >100 kg, 1000 mg). All pts continued background therapy with stable conventional synthetic DMARDs. From Week 12, pts who did not achieve ≥20% improvement in both tender and swollen joint counts vs baseline at 2 consecutive visits had background medication(s) adjusted or added. In this post hoc analysis, pts were grouped by the number and/or type of bDMARD received prior to enrollment: 1) lack of efficacy (LoE) to ≥1 tumor necrosis factor (TNF) inhibitor; 2) LoE to ≥1 interleukin-6 (IL-6) inhibitor; 3) intolerance to prior bDMARDs; 4) number of prior bDMARDs (1, 2, or ≥3). Mean change from baseline in DAS28(CRP) and DAS28(CRP) <2.6 and other clinical endpoints were evaluated at Weeks 12/24. Most pts had LoE to ≥1 TNF inhibitor (536, 87.6%); 96 (15.7%) had LoE to an IL-6 inhibitor; 79 (12.9%) had intolerance to prior bDMARDs; 408 (66.7%), 134 (21.9%), and 64 (10.5%) had received 1, 2, or ≥3 prior bDMARDs, respectively. Mean change from baseline in DAS28(CRP) was generally greater with UPA vs ABA across the different pt subgroups at Weeks 12/24 (Figure 1). Across endpoints, regardless of prior bDMARD therapy (except in those who failed ≥3 prior bDMARDs), UPA and ABA demonstrated similar responses at Week 12 compared with those observed for the overall treatment groups, even with more stringent criteria such as ACR70 and Clinical Disease Activity Index (CDAI) ≤2.8 (Table 1. below) Responses at Week 24 followed a similar trend to those at Week 12 for DAS28(CRP) <2.6 and other endpoints (Table 1). The safety profile across subgroups was consistent with each respective treatment in the overall study population (data not shown). Although sample sizes were small for some subgroups, treatment with UPA led to greater clinical responses vs ABA at Week 12, including in pts with LoE to TNF or IL-6 inhibitors, and those with IR or intolerance to 1, 2, or ≥3 prior bDMARDs. [Display omitted] AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Grant Kirkpatrick, MSc of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Andrea Rubbert-Roth Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Gilead, Janssen, Novartis, Roche, and Sanofi, Ricardo Xavier Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Boulos Haraoui Consultant of: AbbVie, Amgen, Eli Lilly, Gilead, MSD, Pfizer, Sandoz, and UCB, Herbert S.B. Baraf Consultant of: Gilead, Janssen, and UCB, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead, and Janssen, Maureen Rischmueller Consultant of: AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead, Janssen, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, and UCB, Naomi Martin Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Jessica Suboticki Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, John Cush Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, and Novartis. Table 1Efficacy endpoints by prior bDMARD subgroup (Week 12 [top] and Week 24 [bottom])aACR20ACR50ACR70DAS28(CRP)≤3.2DAS28(CRP) <2.6CDAI ≤10CDAI ≤2.8HAQ-DIMCIDbLoE to ≥1 TNF inhibitorUPA 15 mg n=26375.377.944.959.722.838.849.061.230.446.840.758.69.122.875.574.3ABAn=27364.572.933.748.413.224.927.546.512.529.733.749.82.212.565.266.3LoE to ≥1 IL-6 inhibitorUPA 15 mg n=4870.885.437.566.720.829.245.866.725.041.741.758.36.316.778.378.3ABAn=4877.179.241.756.322.927.125.043.814.629.227.152.12.110.475.075.0Intolerance to prior bDMARDsUPA 15 mgn=4783.076.653.257.417.027.753.257.431.929.844.744.78.514.980.073.3ABAn=3262.571.928.150.00.031.321.956.36.331.321.956.33.19.461.367.71 priorbDMARDUPA 15 mgn=20677.281.151.963.121.838.852.466.032.547.641.761.29.220.979.676.6ABAn=20267.377.735.153.515.833.729.251.512.435.636.155.93.016.366.771.72 priorbDMARDsUPA 15 mgn=6478.176.634.456.323.439.151.662.526.650.045.354.74.723.473.870.5ABAn=7064.364.328.642.94.311.427.141.411.424.328.644.31.48.655.755.7≥3 prior bDMARDsUPA 15 mg n=2955.265.524.144.817.224.127.641.420.727.627.648.310.317.258.672.4ABAn=3565.771.440.040.020.017.128.637.120.020.037.140.02.98.677.174.3aMissing information was imputed using NRI. bHAQ-DI MCID=reduction from baseline of ≥0.22ACR20/50/70, 20/50/70% improvement in ACR criteria; HAQ-DI, Health Assessment Questionnaire-Disability Index

Background:Upadacitinib (UPA), an oral, JAK1-selective inhibitor, demonstrated efficacy through 12 and 24 weeks (wks) in phase 3 trials of patients (pts) with active rheumatoid arthritis (RA) and inadequate response (IR) to csDMARDs and bDMARDs, respectively.1,2 Efficacy evaluations at Wk 12 are an important assessment point according to T2T recommendations.3 Objectives:To assess the impact of UPA at 12 wks on individual and composite measures of RA disease activity.Methods:Pts received UPA 15 mg or 30 mg once daily (QD) or PBO for 12 wks in two phase 3 trials. SELECT NEXT1 and SELECT BEYOND2 enrolled csDMARD- and bDMARD-IR pts, respectively. For this investigation, responses at Wk 12, were defined as ≥50% improvement in ACR components. Among ACR50 responders, the proportions of pts achieving ≥50% improvement in all 7 components of the ACR response criteria [Tender Joint Count (TJC68), Swollen Joint Count (SJC66), Pt Global Assessment (PtGA), Physician Global Assessment (PhGA), Pt Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and high sensitive C-reactive protein (hsCRP)] were assessed. Differences in the cumulative distributions of CDAI, DAS28-CRP, and SDAI between baseline (BL) and Wk 12 were assessed. All analyses were based on observed data without imputation.Results:Pts in both studies, on average, had established, moderate to severe RA at BL, with (mean) disease durations of 7.3 and 13.2 years, CDAI of 38.2 and 40.9, in csDMARD-IR and bDMARD-IR pts, respectively; 53% of bDMARD-IR pts had exposure to ≥2 bDMARDs.1,2 In both populations, significantly more pts on UPA vs PBO achieved ≥50% improvement in each ACR component at Wk 12 (Table). Among pts who achieved ACR50 at Wk 12, approximately one-half of the csDMARD-IR and one-third of the bDMARD-IR pts achieved ≥50% improvement in all 7 ACR components. While there were no differences at BL, cumulative distributions of CDAI, DAS28-CRP, and SDAI separated by treatment at Wk 12 (p<0.001); for the lowest quartiles for UPA 15 mg and 30 mg vs PBO, CDAI levels dropped to 6.2 and 5.1 vs 12.5 in csDMARD-IR; and 7.2 and 8.2 vs 13.1 in bDMARD-IR.Conclusions:In pts with an insufficient response to either csDMARDs or bDMARDs, treatment responses at 12 wks were observed in significantly higher proportions with UPA vs PBO. Favorable effects with UPA were seen in the composite scores and the individual parameters, including PROs and acute-phase reactants.References[1]Burmester, et al., Arthritis Rheumatol2017;69:S10.[2]Genovese, et al. Arthritis Rheumatol2017;69:S10.[3]Smolen, et al. 2015. doi:10.1136/annrheumdis-2015-207524Acknowledgements:AbbVie Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie, Inc.Disclosure of Interest:R. van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB, Consultant for: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, R. Dore: None declared, K. Chen Shareholder of: AbbVie, Employee of: AbbVie, H. Camp Shareholder of: AbbVie, Employee of: AbbVie, J. Enejosa Shareholder of: AbbVie, Employee of: AbbVie, T. Shaw Shareholder of: AbbVie, Employee of: AbbVie, J. Suboticki Shareholder of: AbbVie, Employee of: AbbVie, S. Hall: None declared

BackgroundIn patients (pts) with rheumatoid arthritis (RA), treat-to-target recommendations call for adjustment of treatment if a target is not met within 3–6 months of initiation. While some pts continue therapy beyond 3–6 months despite not achieving the target, it’s unclear if they still can achieve the target, and how the timing of target attainment impacts long-term outcomes.ObjectivesTo evaluate clinical, functional, and radiographic outcomes on the basis of initial time to low disease activity (LDA) attainment among early RA pts who are naïve to MTX, or are MTX-insufficient responders (MTX-IR).MethodsThis post hoc analysis included pts receiving MTX in monotherapy or in combination with adalimumab (ADA) in 2 randomised, controlled trials (RCTs) of MTX-naïve pts with early RA: PREMIER included a 104 week (wk) RCT1; OPTIMA included a 26 wk RCT followed by treatment adjustments based on a target of LDA at wks 22 and 262. Pts not achieving stable LDA received open-label (OL) ADA +MTX for an additional 52 wks (MTX-inadequate responders, IR). Pts were subgrouped by treatment and time to first LDA event [SDAI ≤11: 0-<3 months (mths), 3-≤6 mths,>6-≤12 mths]. The following were summarised for each subgroup: mean values and change from baseline in SDAI, HAQ-DI and modified total Sharp score (mTSS). The proportions of pts achieving SDAI remission (REM) at 1 year (yr) were assessed.ResultsRoughly equal proportions of pts on MTX alone experienced their first LDA response between 0-<3 mths (21%), 3-≤6 mths (21%), and >6-≤12 mths (17%). More pts on ADA+MTX experienced LDA within 3 mths (0-<3: 45% and 56% for MTX-naïve and MTX-IR backgrounds, respectively), with smaller proportions in the 3-≤6 mths (19% for both MTX-naïve and –IR backgrounds), and >6-≤12 mths groups (14% and 4% for MTX-naïve and MTX-IR backgrounds). Approximately 50% of the 0–<3 mth group across treatments achieved SDAI REM at 1 year. Interestingly, 10%, 14%, and 8% of the MTX, ADA+MTX (MTX-naïve), and ADA+MTX (MTX-IR) pts who first experienced LDA after 6 mths were in SDAI REM at 1 year.Among MTX-naïve pts, pts on ADA+MTX had greater ΔHAQ and smaller ΔmTSS than pts on MTX alone at Wks 26 and 52 (table 1). Regardless of their time to first SDAI LDA response, pts on MTX monotherapy or ADA+MTX experienced comparable improvements in SDAI, HAQ-DI and comparable ΔmTSS at Wks 26 and 52.Table 1 Mean Values at Baseline and Change From Baseline in Clinical, Functional, and Structural Parameters in Patients with Early RA Receiving MTX or ADA+MTX, on the Basis of First Achievement of Low Disease Activity by SDAI.ConclusionsPts on ADA+MTX achieved a first SDAI LDA response earlier than pts on MTX monotherapy, regardless of whether they were MTX-naïve or MTX-IR. More pts with a very early response went on to achieve SDAI REM at 1 year. However, pts with a longer time (>6 mths) to their first SDAI LDA response had comparable clinical, functional and radiographic outcomes compared to pts who responded earlier (within 3 or 6 mths). Therefore, achieving a clinical response in the direction of the treatment target, even if not yet achieving it, may be sufficient to continue therapy in appropriate pts.References[1] Breedveld, et al. Arthritis & Rheum2006;54:26.[2] Smolen, et al. Lancet2014;383:321.AcknowledgementsAbbVie: study sponsor, contributed to design, data collection, analysis, interpretation; and writing, reviewing, approval of final version. Medical writing: Naina Barretto of AbbVie.Disclosure of InterestJ. Smolen Grant/research support from: AbbVie, Consultant for: AbbVie, X. Bu Shareholder of: AbbVie, Employee of: AbbVie, X. Wang Shareholder of: AbbVie, Employee of: AbbVie, J. Suboticki Shareholder of: AbbVie, Employee of: AbbVie, A. Kavanaugh Grant/research support from: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB., Consultant for: expert advice to AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB