Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians.

To optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging.

Response to ritlecitinib with or without narrow-band UVB add-on therapy in patients with active nonsegmental vitiligo: results from a phase 2b extension study.

Background: Ritlecitinib demonstrated efficacy in a phase 2b trial of nonsegmental vitiligo.

Objective: To evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band UVB (nbUVB) phototherapy in patients with nonsegmental vitiligo.

Methods: Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200mg for 4 weeks then 50mg for 20 weeks, with or without nbUVB phototherapy 2x/week.

Ocean warming and acidification alter calcification and innate immune system gene expression in juvenile American lobsters, Homarus americanus.

The Gulf of Maine, home to American lobster, Homarus americanus, is experiencing rapid ocean warming (OW) and acidification (OA) due to climate change. While some studies have investigated the effects of either ocean acidification (OA) or warming (OW) on lobsters, few explore the interaction of these stressors, particularly on gene expression. We evaluated the effects of OA and OW on early benthic juvenile lobster transcriptomics using RNA sequencing and RT-qPCR through two distinct aquarium experiments.

Evaluating the need for standardised disease manifestation categories in patients infected with the tick-borne encephalitis virus: A Delphi panel.

Categorization systems for tick-borne encephalitis virus (TBEV) infection lack consistency in classifying disease severity. To evaluate the need for a standard, consensus-based categorisation system for TBEV infection across subtypes, we gathered an expert panel of clinicians and scientists with diverse expertise in TBEV infection. Consensus was sought using the Delphi technique, which consisted of 2 web-based survey questionnaires and a final, virtual, consensus-building exercise.

Effectiveness of tofacitinib versus tumor necrosis factor inhibitors and in those receiving tofacitinib as different lines of therapy in patients with rheumatoid arthritis: results from the United States CorEvitas Rheumatoid Arthritis Registry.

Objectives: To compare effectiveness of tofacitinib versus tumor necrosis factor inhibitors (TNFi), and across tofacitinib lines of therapy, in patients with rheumatoid arthritis (RA), using US CorEvitas RA Registry data.

Methods: Analysis included patients with RA initiating tofacitinib or TNFi with a 12-month follow-up visit between November 2012-February 2021. Primary (Clinical Disease Activity Index-defined low disease activity [CDAI-LDA: CDAI ≤ 10]) and secondary (clinical/disease activity/patient-reported) effectiveness outcomes were assessed at month 12.

Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial.

Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).

Patients And Methods: Patients with untreated aRCC (any prognostic risk score) were enrolled.

Chronic rhinosinusitis with nasal polyps (CRSwNP) symptom verbal response scales: content validity testing for use in adults with CRSwNP.

Background: PRO measures of symptoms in clinical trials have historically utilized visual and numerical scales but verbal descriptors may make it easier for patients to clearly differentiate between response options. This study assessed content validity and meaningful change in five verbal response scales (VRSs) used to assess chronic rhinosinusitis with nasal polyp (CRSwNP) symptom severity.

Methodology: This qualitative, semi-structured interview study recruited adults from the US, Germany, and China with confirmed moderate-to-severe CRSwNP.

Comparison of highly sensitive, multiplex immunoassay platforms for streamlined clinical cytokine quantification.

Introduction: Selecting the optimal platforms to quantitate cytokines is challenging due to varying performance and the plethora of options available.

Aims: To compare performance of three highly sensitive, multiplex assays on three different platforms - MSD S-plex, Olink Target 48, and Quanterix SP-X - to MSD V-plex which is widely used for quantitative cytokine assay.

Methods: Serum and stimulated plasma samples were analyzed across each platform.

Risk of adverse events after Omicron XBB-adapted BNT162b2 COVID-19 vaccination in the United States.

Background: Limited data exists regarding the safety of the COVID-19 2023-2024 vaccine formulations and whether the safety profiles differ from the original formulations. We evaluated the association between the BNT162b2 XBB COVID-19 vaccine and the risk of 20 pre-specified adverse events of special interest (AESIs).

Methods: We identified commercially-insured individuals in the US age ≥ 6 months who received the BNT162b2 XBB COVID-19 vaccine between September 11, 2023 and January 15, 2024 within the Optum pre-adjudicated database.

Long-Term Kidney Outcome of Lupus Nephritis by Renal Response Status.

Introduction: Limited evidence exists that clinical trial treatment response criteria predict long-term outcomes in Asian patients with lupus nephritis (LN).

Methods: This retrospective analysis of prospectively collected data from the Hong Kong Queen Mary Hospital Cohort categorized adults with biopsy-proven LN (Class III, IV, V, or mixed [III ± V, IV ± V]) after standard treatment for 2 years postbiopsy and immunosuppression induction according to modified primary efficacy renal response (mPERR: estimated glomerular filtration rate [eGFR] ≥ 60 ml/min per 1.73 m or ≤ 20% below biopsy value AND urine protein-to-creatinine ratio [uPCR] ≤ 0.

Long-term weight loss and cardiorenal outcomes by baseline BMI in the VERTIS CV trial.

Aim: To assess weight loss and cardiorenal outcomes by baseline body mass index (BMI) in VERTIS CV.

Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. These post hoc analyses evaluated cardiometabolic and cardiorenal outcomes (a composite of death from CV causes or hospitalization for heart failure [HHF], CV death, HHF and an exploratory composite kidney outcome including ≥40% estimated glomerular filtration rate [eGFR] decrease) by baseline BMI, using conventional clinical categories and Cox proportional hazards models.

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis.

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).

Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts).

Anemia in Myelofibrosis: A Focus on Proactive Management and the Role of Momelotinib.

Anemia is a common and progressive clinical manifestation of myelofibrosis that may occur as part of the disease pathogenesis as well as due to the myelosuppressive effects of some treatments, with a substantial impact on quality of life, prognosis, and healthcare resource utilization. Despite these burdens, anemia management has traditionally been a secondary priority to spleen and symptom control, due in part to the limitations of available therapeutic approaches. With the initial regulatory approvals of momelotinib, a Janus kinase 1 (JAK1), JAK2, and activin A receptor type 1 inhibitor that provides anemia-related benefits in addition to addressing splenomegaly and symptoms, re-evaluation of anemia as an early and prominent treatment consideration is warranted.

Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials.

Weight and metabolic changes with long-acting cabotegravir and rilpivirine or bictegravir/emtricitabine/tenofovir alafenamide.

Background: Modest weight and lipid changes have been observed in cabotegravir plus rilpivirine long-acting (CAB+RPV LA) Phase 3/3b studies. The SOLAR study included standardized evaluations of weight and metabolic changes in people living with HIV switching to CAB+RPV LA dosed every 2 months (Q2M) vs. continuing bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF).

Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program.

Background: Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy.

Methods: In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively.

Estimated Vaccine Effectiveness for Respiratory Syncytial Virus-Related Lower Respiratory Tract Disease.

Importance: Clinical trials have demonstrated high vaccine efficacy (VE) against lower respiratory tract disease (LRTD) but enrolled a smaller proportion of persons aged 75 years or older and those with comorbidities than seen in highest-risk populations in clinical practice settings. Additionally, VE against respiratory syncytial virus (RSV)-related hospitalizations and emergency department (ED) visits is not yet fully described.

Objective: To estimate Respiratory Syncytial Virus Prefusion F (RSVpreF) effectiveness in older adults.

Treatment patterns and burden of uncomplicated urinary tract infection in England.

Background: Uncomplicated urinary tract infections (uUTIs) are common bacterial infections.

Aim: Evaluate the burden of uUTI in England for 1) potential determinants of disease progression; 2) extent and impact of antimicrobial prescribing non-concordant with treatment guidelines; and 3) economic burden and costs.

Design & Setting: Retrospective cohort study utilising patient data from the Clinical Practice Research Datalink (CPRD) linked to English Hospital Episodes Statistics.

Treatment effect and safety of seltorexant as monotherapy for patients with major depressive disorder: a randomized, placebo-controlled clinical trial.

The antidepressant efficacy and safety of seltorexant monotherapy in major depressive disorder (MDD) was investigated in a placebo-controlled, placebo lead-in, randomized, double-blind, phase 1b study. Participants were randomized to receive seltorexant (20 mg or 40 mg) or placebo. The treatment effect was assessed by changes in the Hamilton Rating Scale for Depression-17 item (HDRS) from treatment-period baseline to week 5 in lead-in placebo non-responders ("enriched" intent-to-treat analysis set).

Patients achieving low lupus disease activity state, systemic lupus erythematosus disease control or remission showed lower rates of organ damage during longitudinal follow-up: analysis of the Hopkins Lupus Cohort.

Objective: One key target of treating patients with systemic lupus erythematosus (SLE) is to prevent organ damage. This analysis quantified the association between time spent in four specific SLE low disease activity (LDA) states and organ damage rate.

Methods: This retrospective real-world data analysis (GSK Study 207168), undertaken to help contextualise the BLISS-BELIEVE clinical trial, included adults with SLE enrolled for≥1 year in the Hopkins Lupus Cohort and treated with standard therapy in a specialist care centre between 1987 and 2019.

Run-in periods and treatment outcomes in asthma trials: A narrative review.

Background: The run-in period is an important element of randomized controlled trials, and is often used in respiratory disease trials. The design of the run-in period can greatly impact results and data interpretation, and as such should be designed carefully.

Methods: In this review, we describe the design of run-in periods across six phase 3A trials of triple therapy in asthma, and discuss how differences in run-in period design (specifically the duration, treatment, and reporting of run-in results) may have the potential to alter the interpretation of study outcomes.

Implementing a Bayesian approach using Stan with Torsten: Population pharmacokinetics analysis of somatrogon.

Fully Bayesian approaches are not commonly implemented for population pharmacokinetic (PK) modeling. In this paper, we evaluate the use of Stan with R and Torsten for population PK modeling of somatrogon, a recombinant long-acting growth hormone approved for the treatment of growth hormone deficiency. As a software for Bayesian inference, Stan provides an easy way to conduct MCMC sampling for a wide range of models with efficient sampling algorithms, and there are several diagnostic tools to evaluate the MCMC convergence and other potential issues.

Acute resistance to BET inhibitors remodels compensatory transcriptional programs via p300 coactivation.

Initial clinical trials with drugs targeting epigenetic modulators - such as bromodomain and extraterminal protein (BET) inhibitors - demonstrate modest results in acute myeloid leukemia (AML). A major reason for this involves an increased transcriptional plasticity within AML, which allows cells to escape the therapeutic pressure. In this study, we investigated immediate epigenetic and transcriptional responses following BET inhibition and could demonstrate that BET inhibitor-mediated release of BRD4 from chromatin is accompanied by an acute compensatory feedback that attenuates down-regulation, or even increases expression, of specific transcriptional modules.