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ObjectivesBimekizumab selectively neutralises both interleukin (IL)-17A and IL-17F. We report efficacy and safety in a phase IIb dose-ranging study in patients with active ankylosing spondylitis (AS).MethodsAdults with AS (fulfilling modified New York criteria) were randomised 1:1:1:1:1 to bimekizumab 16 mg, 64 mg, 160 mg, 320 mg or placebo every 4 weeks for 12 weeks (double-blind period). At week 12, patients receiving bimekizumab 16 mg, 64 mg or placebo were re-randomised 1:1 to bimekizumab 160 mg or 320 mg every 4 weeks to week 48; other patients continued on their initial dose (dose-blind period). The primary end point was Assessment of SpondyloArthritis international Society (ASAS) 40 response at week 12 (non-responder imputation (NRI) for missing data).Results303 patients were randomised: bimekizumab 16 mg (n=61), 64 mg (n=61), 160 mg (n=60), 320 mg (n=61) or placebo (n=60). At week 12, significantly more bimekizumab-treated patients achieved ASAS40 vs placebo (NRI: 29.5%–46.7% vs 13.3%; p<0.05 all comparisons; OR vs placebo 2.6–5.5 (95% CI 1.0 to 12.9)). A significant dose-response was observed (p<0.001). The primary end point was supported by all secondary efficacy outcomes. At week 48, 58.6% and 62.3% of patients receiving bimekizumab 160 and 320 mg throughout the study achieved ASAS40, respectively (NRI); similar ASAS40 response rates were observed in re-randomised patients. During the double-blind period, treatment-emergent adverse events occurred in 26/60 (43.3%) patients receiving placebo and 92/243 (37.9%) receiving bimekizumab.ConclusionsBimekizumab provided rapid and sustained improvements in key outcome measures in patients with active AS, with no unexpected safety findings versus previous studies.Trial registration number NCT02963506.

BackgroundSubcutaneous (SC) administration of KZR-616 (30 and 45 mg weekly [QW]) was demonstrated as safe and well-tolerated, and successfully achieved target levels of immunoproteasome inhibition in healthy volunteers.1,2 MethodsSLE patients in this open-label multicenter dose escalation trial received KZR-616 at doses of 45 mg (Cohort 1), 60 mg (Cohort 2), or 30 mg with escalation to 60 mg (Cohorts 2a and 2b) subcutaneously weekly through Week 13 (W13) with 12 weeks of follow-up.ResultsAs of 16 January 2020, 33 patients had enrolled and received at least 1 dose of KZR-616. The majority of TEAEs have been mild or moderate with no reported peripheral neuropathy, prolonged GI-related AEs, and no clinically significant laboratory AEs. When compared to baseline, improvement in measures of disease activity were seen at W13 and beyond. A single patient with active class IV/V nephritis who failed prior treatment with tacrolimus was enrolled on prednisone 10 mg, leflunomide 10 mg, and hydroxychloroquine 200 mg/day; nephrotic-range proteinuria at baseline (3.85 g/day) decreased to 0.6 g/day 4 weeks after the last dose of KZR-616.ConclusionsWeekly SC administration of KZR-616 at 45 and 60 mg was safe and well-tolerated. Evidence of disease suppression at W13 was observed, and 94% of evaluable patients had improvements on at least 2 measures/assessments of disease activity. In addition, one study participant with active proliferative nephritis (LN) was enrolled with significant reduction in proteinuria. The Phase 2 portion of this study in active proliferative LN is open for enrollment.ReferencesLickliter J. et al. Ann Rheum Dis 2018;77: A1413Furie R, et al. Ann Rheum Dis 2019;78: A776

Background Individuals with Friedreich ataxia (FRDA) can find it difficult to access specialized clinical care. To facilitate best practice in delivering healthcare for FRDA, clinical management guidelines (CMGs) were developed in 2014. However, the lack of high-certainty evidence and the inadequacy of accepted metrics to measure health status continues to present challenges in FRDA and other rare diseases. To overcome these challenges, the Grading of Recommendations Assessment and Evaluation (GRADE) framework for rare diseases developed by the RARE-Bestpractices Working Group was adopted to update the clinical guidelines for FRDA. This approach incorporates additional strategies to the GRADE framework to support the strength of recommendations, such as review of literature in similar conditions, the systematic collection of expert opinion and patient perceptions, and use of natural history data. Methods A panel representing international clinical experts, stakeholders and consumer groups provided oversight to guideline development within the GRADE framework. Invited expert authors generated the Patient, Intervention, Comparison, Outcome (PICO) questions to guide the literature search (2014 to June 2020). Evidence profiles in tandem with feedback from individuals living with FRDA, natural history registry data and expert clinical observations contributed to the final recommendations. Authors also developed best practice statements for clinical care points that were considered self-evident or were not amenable to the GRADE process. Results Seventy clinical experts contributed to fifteen topic-specific chapters with clinical recommendations and/or best practice statements. New topics since 2014 include emergency medicine, digital and assistive technologies and a stand-alone section on mental health. Evidence was evaluated according to GRADE criteria and 130 new recommendations and 95 best practice statements were generated. Discussion and conclusion Evidence-based CMGs are required to ensure the best clinical care for people with FRDA. Adopting the GRADE rare-disease framework enabled the development of higher quality CMGs for FRDA and allows individual topics to be updated as new evidence emerges. While the primary goal of these guidelines is better outcomes for people living with FRDA, the process of developing the guidelines may also help inform the development of clinical guidelines in other rare diseases.

Covering an era from the early twentieth century to the present, this volume features twenty-seven South Carolina women of varied backgrounds whose stories reflect the ever-widening array of activities and occupations in which women were engaged in a transformative era that included depression, world wars, and dramatic changes in the role of women. Some striking revelations emerge from these biographical portraits-in particular, the breadth of interracial cooperation between women in the decades preceding the civil rights movement and ways that women carved out diverse career opportunities, sometimes by breaking down formidable occupational barriers. Some women in the volume proceeded cautiously, working within the norms of their day to promote reform even as traditional ideas about race and gender held powerful sway. Others spoke out more directly and forcefully and demanded change. Most of the women featured in these essays were leaders within their respective communities and the state. Many of them, such as Wil Lou Gray, Hilla Sheriff, and Ruby Forsythe, dedicated themselves to improving the quality of education and health care for South Carolinians. Septima Clark, Alice Spearman Wright, Modjeska Simkins, and many others sought to improve conditions and obtain social justice for African Americans. Others, including Victoria Eslinger and Tootsie Holland, were devoted to the cause of women's rights. Louise Smith, Mary Elizabeth Massey, and Mary Blackwell Butler entered traditionally male-dominated fields, while Polly Woodham and Mary Jane Manigault created their own small businesses. A few, including Mary Gordon Ellis, Dolly Hamby, and Harriet Keyserling exercised political influence. Familiar figures like Jean Toal, current chief justice of the South Carolina Supreme Court, are included, but readers also learn about lesser-known women such as Julia and Alice Delk, sisters employed in the Charleston Naval Yard during World War II.