Metroplex Clinical Research Center

Predictive biomarkers for patients with early rheumatoid arthritis (RA) are needed. This exploratory post hoc analysis investigated inflammatory biomarkers associated with baseline disease activity and biomarkers predictive of treatment response in patients who were seropositive with early RA from a phase 3 study. The AVERT-2 study (NCT02504268) included patients who were disease-modifying antirheumatic drug naive and anti-citrullinated protein antibody positive randomized to abatacept and methotrexate (MTX) or placebo and MTX for 56 weeks. Correlations were assessed among biomarkers and disease activity, pharmacodynamic (PD) changes on disease-associated biomarkers in response to treatment, and baseline biomarkers to predict treatment response at week 52. In the analysis, 446 patients received abatacept and MTX and 300 received placebo and MTX. Of 103 biomarkers, 47 demonstrated a significant reduction in PD changes with abatacept and MTX versus placebo and MTX, with 18 out of 47 biomarkers showing correlations with baseline disease activity. High baseline interleukin-10 (IL-10) levels were associated with greater probability of achieving efficacy measures by week 52 in patients receiving abatacept and MTX versus placebo and MTX, consistent with a significant reduction in disease activity with abatacept and MTX (P < 0.03 to P < 0.0007). Higher baseline IL-10 levels were associated with lower bone erosive development with abatacept and MTX compared with placebo and MTX. Treatment with abatacept and MTX resulted in significantly greater reduction of biomarkers relevant to RA, and high baseline IL-10 levels predicted better treatment response with abatacept and MTX versus placebo and MTX across clinical outcomes. Findings suggest a well-suited mechanism of action for abatacept and MTX in patients with early RA and high baseline IL-10 levels.

Background/Objectives: Baseball pitchers accumulate extreme upper extremity forces during the repetitive, high-velocity motion of throwing, which can lead to shoulder dysfunction and overuse injuries. Although scapular dyskinesis has been linked to various shoulder pathologies, there is a lack of evidence on the specific scapular patterns predisposing pitchers to injury. Methods: A total of 85 professional pitchers from a single professional baseball organization participated in the entirety of this study. All subjects had their scapular positions and motion patterns measured via a digital goniometer prior to the beginning of a competitive season. Scapular upward/downward rotation, anterior/posterior tilt, and internal/external rotation were assessed with the shoulder at rest and during elevation to 120° in the scapular plane. Overuse injuries of the shoulder/elbow sustained during the subsequent competitive season were documented by the team’s medical staff, with statistical comparisons between the injured (n = 34) and non-injured (n = 51) group for each scapular measure. Results: Pitchers who sustained shoulder/elbow injuries demonstrated significantly more scapular anterior tilt during humeral elevation compared to those without an injury (p = 0.04). The difference in anterior tilt between the two groups was 3.8° and had a medium effect size, suggesting clinical relevance. No significant between-group differences were found in any other scapular positions or motions (p > 0.22). Conclusions: Pitchers with increased scapular anterior tilt were more likely to sustain a shoulder/elbow injury, highlighting this kinematic feature as a potential risk factor. This finding suggests that anterior tilt might contribute to soft tissue strain, increasing injury susceptibility in pitchers.

Aim: Scope of this work aims to explore the effectiveness of AI-powered outbound dialer campaigns with legacy outbound dialer campaigns by evaluating their technological capabilities, operational efficiencies, compliance features, customer experience impact, cost-effectiveness, and scalability. Study Design: This is a comparative analysis study evaluating two types of outbound dialer systems used in customer engagement campaigns. Place and Duration of Study: This study is based on a review of industry practices and integration strategies in contact centers across various organizations, focusing on solutions implemented between 2018 and 2024. Methodology: This study employed a comparative analysis methodology to evaluate AI-powered and legacy outbound dialer campaigns. The research was conducted through secondary data collection from industry reports, case studies, and real-world deployment insights over a study period spanning 2018 to 2024. Key performance metrics assessed included call connection rates, compliance adherence, personalization capabilities, operational costs, and scalability. Data was synthesized using a structured comparative framework to highlight technological, operational, and customer experience differences. Qualitative evaluations of agent productivity and customer satisfaction were also incorporated to provide a holistic analysis. Results: AI-powered outbound dialers demonstrated superior efficiency with call connection rates increasing by up to 30% compared to legacy systems. Automated regulatory monitoring strengthened compliance adherence, cutting violation risks by 40%. Personalization capabilities drove a 25% increase in customer satisfaction scores, while automation initiatives reduced operational costs by 20%. In contrast, legacy dialers faced higher abandonment rates and lacked real-time adaptability. Scalability and omnichannel integration were also more seamless in AI-powered systems, supporting modern customer engagement strategies. Conclusion: AI-powered outbound dialers outperform legacy systems in nearly all critical aspects, including efficiency, compliance, personalization, and cost-effectiveness. They provide a scalable, adaptive solution for businesses aiming to optimize customer engagement. While legacy systems may still be viable in smaller or less dynamic operations, AI-driven technologies are emerging as the preferred choice for future-proof outbound campaigns. Further adoption of AI-powered systems will continue to redefine industry standards.

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors.

Janus kinase inhibitors (JAKi) have been available for the treatment of rheumatoid arthritis (RA) since 2012 and are indicated for patients with active disease despite csDMARD therapy. Efficacy and safety, as demonstrated in the clinical trials, was similar to biologics. A recent post marketing trial suggested safety concerns with the JAKi, which will be reviewed. A post marketing Food and Drug Administration (FDA) mandated open-label randomized clinical trial of tofacitinib 5 and 10 mg twice daily (b.i.d.) compared with adalimumab and etanercept was conducted in RA patients on background methotrexate who were at a high risk for cardiovascular disease. This was a noninferiority study evaluating the incidence of major adverse cardiovascular events (MACE) and malignancy with the therapies. Noninferiority for both doses of tofacitinib was not achieved with a numerical increase in MACEs and malignancy with tofacitinib compared to the TNF inhibitors. A dose-dependent increase in venous thromboembolism (VTE) risk with tofacitinib was observed. The findings from this study resulted in the FDA and European Medicines Agency (EMA) restriction of use for all Jaki to RA patients who had failed TNF inhibitors. JAK inhibitors are effective treatments for RA. Issues have been raised regarding safety in patients with an increase in cardiovascular risk and VTE risk resulting in the need for risk stratification.

Objectives To assess the efficacy and safety of olokizumab (OKZ), a monoclonal antibody against the interleukin-6 (IL-6) cytokine, versus placebo (PBO) in patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IRs).Methods In this 24-week multicentre, placebo-controlled, double-blind study, the patients were randomised in a 2:2:1 ratio to receive subcutaneously administered OKZ 64 mg once every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or PBO plus methotrexate. At week 16, the patients on PBO were randomised to receive either OKZ regime. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. Disease Activity Score 28-joint count C-reactive protein (DAS28 (CRP)) &lt;3.2 at week 12 was the major secondary efficacy endpoint. Safety and immunogenicity were assessed.Results In 368 patients randomised, ACR20 response rates were 60.9% in OKZ q2w, 59.6% in OKZ q4w and 40.6% in PBO (p&lt;0.01 for both comparisons). Achievement of DAS28 (CRP) &lt;3.2 was significantly different, favouring the OKZ arms. Improvements in efficacy and patientreported outcomes were maintained throughout 24 weeks and were noted after week 16 in patients who switched from PBO.Dose-related treatment-emergent serious adverse events were 7% in OKZ q2w, 3.2% in OKZ q4w and none in the PBO group.Conclusions Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNFi-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.

IntroductionThe efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs.MethodsPatient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847). For the MAIC, individual patient data from the TARGET trial were assigned weights such that weighted mean baseline characteristics of the treatment effect modifiers matched those from SELECT-BEYOND. For the STC, the TARGET patient-level data and mean baseline values from SELECT-BEYOND were used to simulate sarilumab treatment effects for a SELECT-BEYOND population. Endpoints evaluated included the American College of Rheumatology (ACR) response criteria ACR20/50/70, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) < 3.2, DAS28-CRP < 2.6, Simple Disease Activity Index (SDAI) < 3.3, and Clinical Disease Activity Index (CDAI) < 2.8 at 12 weeks.ResultsThe analysis included 365 patients from TARGET and aggregated data of 333 patients from SELECT-BEYOND. Matching for potential treatment effect baseline modifiers (i.e., age, oral glucocorticoid use, tender joint count of 68 counts, swollen joint count of 66 counts, serum CRP level, and patient global assessment of disease activity) resulted in a reduction of the effective sample size of TARGET population to 166. Following MAIC and STC analysis, the odds of achieving all aforementioned clinical outcomes versus placebo at week 12 were similar for sarilumab and upadacitinib.ConclusionIn the MAIC and STC analyses from TARGET and SELECT-BEYOND trials, the efficacy of sarilumab and upadacitinib were comparable.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00521-1.

An Outside of the healthcare industry, commercially available artificial intelligence (AI) algorithms have shown signs of racial, gender, and societal prejudice. The development of AI algorithms in the fields of radiologic sciences and healthcare is significantly impacted by these biases. The physician community should work with developers and regulators to create paths that guarantee algorithms sold for widespread clinical practice are secure, efficient, and free of unintended bias in order to prevent the introduction of bias in healthcare AI. Structured AI use cases with data elements have been developed by the ACR Data Science Institute to make it easier to create standardized datasets for AI testing and training at various universities. This project seeks to encourage the accessibility of a variety of data for algorithm development. Additionally, ACR Certify-AI and ACR Assess-AI, validation and monitoring services offered by the ACR Data Science Institute, integrate guidelines for minimizing algorithm bias and advancing health fairness. The ACR should support pricing methods for AI that guarantee access to AI technologies for all patients, regardless of their socioeconomic level or the resources available within their healthcare systems, in addition to promoting diversity. The ACR Data Science Institute conducted its first annual survey of ACR members to better understand how artificial intelligence (AI) is used in clinical practice and to create a baseline for tracking trends. Participants were asked to answer questions about their practice's demographics and to say whether or not they presently use AI in their clinical work, as well as in what capacity. AI has started to be used in mammography screening procedures. According to the report, larger practices were more likely to use AI than smaller ones. The majority of individuals who used AI in clinical practice did so to improve interpretation; the most frequent uses were for the early detection of cerebral hemorrhage, pulmonary emboli, and abnormalities in mammograms. According to the survey results, clinical practice has just recently begun to incorporate AI at a moderate rate. The data acquired from the poll will help researchers and business experts create AI solutions that can improve radiological practice, resulting in enhancements to the effectiveness and quality of patient care.