Wolfeserrano5939

Compared with patients receiving placebo, those receiving ziltivekimab experienced significantly greater reductions of high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen from baseline to end of treatment. Median ESA usage decreased by 15,000, 15,000, or 33,000 IU/wk per patient in the 2-, 6-, and 20-mg ziltivekimab cohorts, respectively, compared with no change in the placebo group. We also noted significant dose responses for decreased ESA resistance index and increased serum iron, total iron binding capacity, transferrin saturation, and serum albumin.

Ziltivekimab significantly improved markers of inflammation, reduced ESA requirements, and increased serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy.

Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.

Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.

Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.

We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.

We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10

). https://www.selleckchem.com/products/Idarubicin.html Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r

=-0.242) and non-albumin protein (r

=0.238).

This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Upadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at least one biologic disease-modifying antirheumatic drug (DMARD).

In this 24-week randomised, placebo-controlled, double-blind, phase 3 trial, 642 patients were randomised (2211) to once per day upadacitinib 15 mg or 30 mg, placebo followed by upadacitinib 15 mg or placebo followed by upadacitinib 30 mg at week 24. The primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 12. Achievement of minimal disease activity (MDA) was assessed at week 24. Treatment-emergent adverse events are reported for all patients who received at least one dose of trial drug.

At week 12, significantly more patients receiving upadacitinib 15 mg and 30 mg versus placebo achieved ACR20 (56.9% and 63.8% vs 24.1%; p<0.001 for both comparisons). At week 24, MDA was achieved by more upadacitinib 15 mg-treated (25.1%) and 30 mg-treated patients (28.9%) versus placebo (2.8%; p<0.001 for both comparisons). Generally, the rates of treatment-emergent adverse events were similar with placebo and upadacitinib 15 mg and higher with upadacitinib 30 mg at week 24. Rates of serious infections were 0.5%, 0.5% and 2.8% with placebo, upadacitinib 15 mg and upadacitinib 30 mg, respectively.

In this trial of patients with active PsA who had inadequate response or intolerance to at least one biologic DMARD, upadacitinib 15 mg and 30 mg was more effective than placebo over 24 weeks in improving signs and symptoms of PsA.

NCT03104374.

NCT03104374.

Rotator cuff disease (RCD) causes prolonged shoulder pain and disability in adults. RCD is a continuum ranging from tendinopathy to full-thickness tendon tear. Recent studies have shown that subacromial decompression and non-surgical treatments provide equivalent results in RCD without a full-thickness tendon lesion. However, the importance of surgery for full-thickness tendon tears remains unclear.

In a pragmatic, randomised, controlled trial, 417 patients with subacromial pain underwent 3-month initial rehabilitation and MRI arthrography (MRA) for the diagnosis of RCD. Of these, 190 shoulders remained symptomatic and were randomised to non-surgical or surgical treatments. The primary outcomes were the mean changes in the Visual Analogue Scale for pain and the Constant Murley Score for shoulder function at the 2-year follow-up.

At the 2-year follow-up, both non-surgical and surgical treatments for RCD reduced pain and improved shoulder function. The scores differed between groups by 4 (95% CI -3 to 10, p=0.25) for pain and 3.4 (95% CI -0.4 to 7.1, p=0.077) for function. Among patients with full-thickness ruptures, the reduction in pain (13, 95% CI 5 to 22, p=0.002) and improvement in function (7.0, 95% CI 1.8 to 12.2, p=0.008) favoured surgery.

Non-surgical and surgical treatments for RCD provided equivalent improvements in pain and function. Therefore, we recommend non-surgical treatment as the primary choice for patients with RCD. However, surgery yielded superior improvement in pain and function for full-thickness rotator cuff rupture. Therefore, rotator cuff repair may be suggested after failed non-surgical treatment.

ClinicalTrials.gov, NCT00695981 and NCT00637013.

ClinicalTrials.gov, NCT00695981 and NCT00637013.