Patients Completed Treatment Research Articles

Curative treatment for oligometastatic gastroesophageal cancer– results of a prospective multicenter study

PurposeOligometastatic gastroesophageal cancer is a clinical entity with no standard treatment recommendation. Treatment with curative intent has recently emerged as an option for selected patients in contrast to the traditional palliative treatment strategy. This prospective study aimed to assess the safety and efficacy of combined systemic and local treatment with curative intent for patients with oligometastatic gastroesophageal cancer.MethodsIn a multicenter study, consecutive patients with gastroesophageal cancer and metastases in the liver and/or extra-regional lymph nodes were screened for inclusion. Eligible patients were offered curatively intended perioperative chemotherapy followed by surgical resection or liver ablation. Primary endpoints were treatment safety and feasibility. Secondary outcomes included postoperative mortality, treatment response, progression-free survival, and overall survival. Subgroup analyses were stratified based on oligometastatic location.ResultsA total of 29 (82.9%) patients completed treatment with surgical resection (93.1%), liver ablation (3.4%), or definitive chemoradiotherapy (3.4%). Postoperative complications were found in 19 (73.1%) patients, whereas postoperative mortality was 0%. The most common complications included infection (34.6%) and respiratory complications (34.6%). Median overall survival was 20.9 months (interquartile range 11.2–42.6) from diagnosis and 17.0 months (interquartile range 6.4–35.9) from surgery in patients who were treated with neoadjuvant chemotherapy followed by surgery. Median progression-free survival was 5.8 months (interquartile range 3.1–11.3).ConclusionThis study found curative treatment to be a relatively safe option, with an overall survival of 20.8 months and no postoperative mortality.

Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study.

Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC. This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data. Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment. This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.

CTIM-27. DOC1021 CELL-BASED VACCINATION AS ADJUVANT THERAPY FOR GLIOBLASTOMA: PHASE I CLINICAL TRIAL ANALYSIS

Abstract Glioblastoma is an aggressive tumor for which median survival remains 14-18 months despite aggressive standard of care. Cellular immunotherapy approaches have recently shown promise. Homologous antigenic loading is an ex-vivo technique that leverages p38MAPK and mTORC1 signaling cascades to initiate powerful cDC1-like skewing in monocyte-derived dendritic cells, leading to downstream induction of tissue-infiltrating, cytolytic effector memory T-cells. This open-label phase I clinical trial evaluated the autologous dendritic cell vaccine DOC1021 prepared through homologous antigenic loading and administered bilaterally near the deep cervical lymph nodes. Three courses of vaccine were administered every 2 weeks after completion of chemoradiation, adjuvanted concurrently with six weeks of weekly type I interferon. Four dose levels from 3.5x106 to 3.6x107 total vaccine cells were tested. Tumor progression prior to vaccination was not an exclusion criterion. Sixteen newly diagnosed IDH-WT patients completed treatment, median age 63 years and 94% MGMTp unmethylated. The most common related AEs were grade 1 injection-site reactions and grade 1-3 fatigue and urticaria. No DLTs were observed. Immunohistochemistry of tumors derived from early post-vaccination second resections showed enhanced CD8+ T-cell infiltration and pathologic findings consistent with residual rather than relapsed GBM in 2/3 patients. Analysis of post-vaccination PBMC in dose level cohorts 2-4 indicated expansion of both CD4+ (13/13) and CD8+ (11/13) central memory T-cell compartments (p&amp;lt;0.002 and p&amp;lt;0.05, respectively) as well as expansion of CD8+CD127+ T-cells (12/13; p&amp;lt;0.001). Among three patients for whom tissue was obtained pre- and post-vaccination, clinical outcomes correlated with Visium spatial transcriptomic analysis. Median survival for the MGMTp unmethylated cohort (n=15) has not yet been reached but is statistically greater (p&amp;lt;0.05) than that of matched historic controls. The results indicate that DOC1021 is safe, can be effectively integrated within existing standards of care and is potentially efficacious in a challenging patient population.

Socioeconomic Deprivation Correlates With Incomplete Radiotherapy Treatment in Head and Neck Cancer

There is a high burden of socioeconomic deprivation across Merseyside and, along with this, poorer cancer outcomes. The incidence of head and neck squamous cell carcinoma (HNSCC) within this region is higher than the national average and there are often additional complexities to individual treatment pathways such as poor health literacy, lack of social support and transport options which can impact on adherence to prescribed treatments. AimsThis work aims to understand the impact of deprivation on patients diagnosed with HNSCC undergoing chemoradiotherapy (CRT) or radiotherapy (RT) treatment by identifying barriers to adherence. Materials and methodsPatients with HNSCC treated between June 2022 and June 2023 were included and data was collected through retrospective case note review. Approval was obtained from relevant NHS institution audit departments. Key examined variables were indices of multiple deprivation (IMD), unplanned admission rate, hospital transport use, social support network and provision of additional ad hoc appointments during treatment courses. All were correlated with missed radiotherapy appointments. ResultsOut of 359 evaluable patients there were high levels of unplanned appointments with health professionals during CRT/RT (71% of those receiving CRT and 55% of those having RT). 11% (n = 39) missed at least one radiotherapy appointment with the commonest reason being unplanned admission to hospital. Despite missed appointments, 25/39 patients completed treatment within prescribed window due to effective RT compensation strategies. On multivariate analysis, unplanned admission, hospital-provided transport and crime deprivation quintiles (p=<0.001, p = 0.007 and p = 0.027, respectively) were found to significantly increase the chance of missed radiotherapy treatment appointments. ConclusionHigh levels of unplanned encounters with health care professionals are encouraging adherence to non-surgical HNSCC treatments. Formalising these ad hoc appointments will provide an equitable, robust service. Undertaking hospital transport increases the potential for missed treatment appointments. Gaining insight into patient experiences and investing in improved transport services are essential for maximising adherence.

Mechanisms of functional asymmetry of the face formation in patients with dysfunctional condition of temporomandibular joint

Objective. To give a detailed description of clinical manifestations, diagnosis and treatment of functional asymmetry of the face in patients with dysfunctional condition of temporomandibular joint (TMJ). Materials and methods. A complete examination of 34 (25 %) patients with symptomatic facial asymmetry of the 3rd type according to H.S. Hwang classification was carried out. The group consisted of 5 males (14,71 %) and 29 females (85,29 %). Screening protocol included standard dental care, cone beam computer tomography of both jaws and TMJ, MRI of TMJ with functional load. Results. 24 patients (70.59 %) completed complex dental treatment; 10 (29.41 %) people stopped treatment for various reasons and were excluded from further study. Complete restoration of facial symmetry was achieved in 21 people (87.5 %), partial restoration in 3 (12.5 %) patients. The height of the lower facial part and the synchrony of occlusal contacts were restored in all patients. Noise in the joint area persisted in 3 (8.8 %) cases, which is associated with arthrosis in the articular heads. In patients with unreducible dislocations, the intensity of the clicks decreased, and there was no pain at the end of treatment. It should be noted that all patients of this group refused subsequent surgical treatment. Conclusion. Functional asymmetry of the face results from multifactorial impact on the human organism and is multimorbid by nature. This condition is accompanied by complicated dental pathology, such as increased hard tooth tissues attrition, functional overload with traumatic nodes formation, disturbance of muscles and TMJ functions. It requires following diagnostic and treatment algorithm under the supervision of internal medicine specialists to correct sleep, postural stability, impaired psychoneurological status.

Safety and Effectiveness of Two Different Fluid-Filled Intragastric Balloons: A Single Center Experience.

The aim of the study is to compare weight loss and safety outcomes of two different commonly available fluid-filled intragastric balloons (IGBs) used for weight loss. A retrospective cohort study of a prospectively maintained database of adult patients who underwent IGB insertion between July 2020 and November 2021 in a single private clinic in Kuwait. The patient either received the Elipse™ or Orbera365™ balloon and was followed until the end of treatment. A total of 358 patients were included, of which 265 and 93 each received the Elipse and Orbera365 balloons, respectively. The mean age of patients was 32.8 (SD 9), the mean body mass index (BMI) was 35kg/m2 (SD 4.8), and 72.1% of patients were female. In the Elipse group, 254 patients completed treatment, and 84 patients completed the treatment with Orbera365. Weight loss outcomes were measured at the end of treatment: 4months after Elipse insertion, and 12months after Orbera365 insertion. Interim 4months weight loss outcomes were also measured for the Orbera365 balloon. Patients in the Orbera365 group had significantly better total body weight loss (%TBWL, 14.7kg [SD 8.9]) compared to the Elipse group (%TBWL 10kg, [SD 5.6], p ≤ 0.0001) at the end of treatment, while there was no difference in weight loss outcomes between the two balloons at 4months. There were more complications requiring premature balloon removal in the Orbera365 group (9.7%) compared to the Elipse group (3.4%). IGBs provide significant weight loss with an acceptable safety profile. The Orbera365 ballon shows better weight loss outcomes compared to the Elipse, likely due to longer duration of treatment. However, there was a higher rate of complications requiring premature balloon removal in the Orbera365 group. Studies with larger patient cohort is needed to verify the findings of this study.

Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study

Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.

Lnsights into Adjuvant Systemic Treatment Selection for Patients with Stage III Melanoma: Data from the Dutch Cancer Registry.

Patient demographics and shared decision making might influence the choice of adjuvant therapy for stage III melanoma. To identify factors for treatment selection of patients diagnosed with stage III melanoma to better understand current treatment decisions and improve further treatment counseling. Data from 2007 patients diagnosed with stage III melanoma, between December 2018 and 2021, sourced from the Dutch Cancer Registry, were analyzed. Among the cohort, 48.7% received no therapy, 45.8% received checkpoint inhibition, and 5.5% received targeted therapy (TT). Patients foregoing therapy were significantly older [67.0 years (range 53.0-77.0) vs. 62.0 year (range 52.0-72.0)], had poorer performance scores (PS), and higher Charlson Comorbidity Index scores compared to those receiving therapy (p<0.001). Patients undergoing therapy had significantly higher median Breslow thickness (3.3mm vs. 2.2mm) and higher prevalence of ulceration (49.9% vs. 38.1%). Those with connective tissue disease and/or congestive heart disease were more likely to receive TT [odds ration (OR) 8.1; 95% confidence interval (CI) 1.7-37.6 and OR 9.3; 95% CI 1.2-72.2, respectively]. Median treatment time among strata for disease recurrence was 4.26months (3.69-4.82) for immunotherapy and 3.1months (0.85-5.36) for TT (p=0.298). Patients who developed recurrent disease were equal across treatment types (p=0.656). The number of patients with grade 3 complications was different for each treatment type [immunotherapy: 17.8% vs. TT: 37.3% (p<0.001)]. Age, PS, and Breslow thickness seem to influence adjuvant treatment decisions. Clinicians' preference for immunotherapy might play a role in counseling BRAF-positive patients for adjuvant therapy, this however, cannot be confirmed in this dataset. Overall, only a small proportion of patients completed adjuvant treatment.

Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study.

Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID)

BackgroundTrimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death.MethodsAdults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6–29) and 28-day all-cause mortality (Days 1–29).ResultsOne-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable.A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 109/L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: −4.46, 34.78; P = 0.096).ConclusionAlthough there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation.ESsCOVID was registered prospectively at ClinicalTrials.gov on October 6, 2020.NCT04576728

Stereotactic centralized ablative radiation therapy: A novel methodology in treating bulky tumor and its technical realization.

159 Background: Bulky tumors pose significant challenges to traditional treatment modalities such as surgery, chemotherapy, and conventional radiotherapy. This study introduces a novel therapeutic approach named as Stereotactic-Core-Ablative-Radiation-Therapy (SCART), designed to deliver an ablative dose to a substantial core of the bulky tumor while quickly decreasing to a lower dose at the tumor periphery. Methods: A SCART-Treatment-Volume (STV) at the core of the GTV was predefined to administer an ablative radiation dose, aiming to induce DNA damage in cancer cells and potentially trigger biological cancer-killing effects. Utilizing Linac-based VMAT or Cyberknife techniques with 6MV photon beams, multiple radiation fields intersect and optimize at STV, generating an ablative dose at the STV. The dose rapidly diminishes to a safe level at the edge of GTV sparing the surrounding tissue. In the phase-1 trial, nineteen patients with 21 bulky tumors enrolled, receiving SCART at five dose levels (15GyX1, 15GyX2, 15GyX3, 18GyX3, 21GyX3, and 24GyX3), while maintaining the GTV's peripheral dose at 5Gy each fraction. Results: All patients completed treatment with average beam-on time of 8.9min and average treatment time of 18.5min. Mean follow-up time is 15.4 month. No grade-III or higher toxicity was observed. 7/19 patients still survive, with the overall survival of 40% at 30 months. Mean tumor volume shrinks by 60% between initial 301cc and post-SCART volumes of 118cc. Long-term follow-up revealed that 14/21 tumors achieved Partial Response, 2/21 Complete-Response, 3/21 Stable-Disease, and 1/21 Progressive-Disease, leading to an encouraging local control of 95%. Conclusions: SCART emerges as a safe and effective strategy for treating bulky malignant tumors, demonstrating excellent local control and overall survival. Multiple treatment courses were feasible. The results from phase-1 study suggest that SCART could revolutionize the treatment landscape for bulky tumors, offering a promising avenue for further exploration and application in clinical practice.

Preliminary analysis of PD-1 inhibitors combined with chemotherapy as neoadjuvant therapy for local advanced non-small cell lung cancer (NSCLC).

200 Background: The benefits of neoadjuvant immunotherapy and chemotherapy for resectable NSCLC suggest that this combined treatment may provide more surgical opportunities and survival benefits for potentially resectable locally advanced NSCLC. Methods: We retrospectively collected data from 28 patients with stage III EGFR/ALK/ROS wild-type NSCLC. Eligible patients received 2-8 cycles of neoadjuvant chemoimmunotherapy (squamous carcinoma: PD-1 inhibitor combined with albumin-bound paclitaxel and cisplatin/carboplatin; adenocarcinoma: PD-1 inhibitor combined with pemetrexed and carboplatin), followed by re-evaluation for surgery. Afterwards, patients underwent surgery after downstaging, with some receiving adjuvant immunotherapy maintenance for one year. Primary endpoints included major pathological response (MPR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: All 28 patients were male, with 7 (25%) in stage IIIA, 10 (35.7%) in IIIB, 4 (14.3%) in IIIC, 2 (7.14%) in IVA, and 2 (7.14%) in IVB. There were 22 cases of squamous cell carcinoma, 4 of adenocarcinoma, 1 of large cell lung cancer, and 1 of lymphoepithelioma-like carcinoma. 23 patients (82.1%) completed neoadjuvant treatment and underwent resection, achieving 100% R0 resection rate (23/23); 5 patients did not undergo surgery, 3 of whom received combined radiochemotherapy due to disease progression, 1 delayed surgery due to immunotherapy associated myocardial damage, and 1 died from massive hemoptysis and hemorrhagic shock. The objective response rate (ORR) was 60.7%, 95%CI [40.6-78.5%] and the disease control rate (DCR) was 85.7%, 95%CI [67.3-96.0%]. Among the 23 patients who underwent surgery, the pCR was 60.9%, 95%CI [38.5-80.3%], MPR was 4.3%, 95%CI [0.1-21.9%], clinical downstaging rate was 50%, 95%CI [30.6-69.4%] and pathological downstaging rate was 86.9%, 95%CI [66.4-97.2%]. 17 patients (77.3%) underwent lobectomy, and 5 (22.7%) underwent bilobectomy with a median blood loss of 100 ml, IQR [55.0-100]. There were no surgery-related deaths. Postoperatively, one patient developed chylothorax, one had a lung infection, and the two improved after conservative treatment. 11 patients (47.8%) received post-surgery immunotherapy maintenance, and 2 of them (8.7%) developed immune-related pneumonia. As of April 7, 2024, the median follow-up time was 21.5 months (95%CI: 17-34 Mo), At 12 months。 PFS rate was 82.1% (95%CI: 69.1-97.6%); OS rate was 96.3% (95%CI: 89.4-100%). Conclusions: Neoadjuvant immunotherapy combined with surgery for unresectable locally advanced NSCLC may benefit patients and significantly extend survival.

Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study.

Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics. This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every4weeks (Q4W); guselkumab at Weeks0and 4, thenQ8W; or placebo with crossover to guselkumab Q4W at Week24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders. 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week100. Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

Long-term immune changes in patients with relapsed/refractory chronic lymphocytic leukemia following treatment with venetoclax plus rituximab.

Immune dysregulation is a hallmark of chronic lymphocytic leukemia (CLL). Anti-CD20 antibodies (e.g., rituximab [R]) can be combined with venetoclax (Ven) to treat CLL. However, anti-CD20 antibodies can increase hypogammaglobulinemia risk, while the effects of Ven on immune dysregulation are still uncertain. We report long-term immune changes in VenR- and bendamustine-R (BR)-treated patients with relapsed/refractory CLL in the MURANO trial (NCT02005471). Patients were randomized to fixed-duration VenR (2 years Ven; VenR for the first 6 months) or BR (6 months). Immune cell levels were evaluated at the end of combination treatment (EOCT), end of treatment (EOT; VenR arm only), and 12 and 24 months post-EOCT. Overall, 130/194 VenR- and 134/195 BR-treated patients completed treatment without progressive disease. In patients who completed VenR combination therapy, median immunoglobulin (Ig)G and IgM levels decreased from baseline to EOT (p ≤ 0.01 and p ≤ 0.0001, respectively); by 24 months, post-EOT IgG had returned to baseline level and IgM had increased from baseline (p ≤ 0.001). Median IgA levels increased from baseline to 12 (p ≤ 0.0001) and 24 months post-EOT (p ≤ 0.0001). In BR-treated patients, changes in IgG, IgA, and IgM levels across the assessed time points were not significant, and by 24 months, post-EOCT IgG, IgA, and IgM were above baseline levels. Grade ≥3 infection rates on treatment were low. Overall, immune recovery was observed with VenR and BR, with stabilization of Ig levels after treatment. Post-treatment infection rates were generally low, making these very tolerable therapies for CLL.

Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors.

Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified inthe IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p<0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p<0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi.

Impact of real-world implementation of evidence-based insomnia treatment within a large payor-provider health system: initial provider and patient-level outcomes.

Insomnia has substantial and wide-ranging negative effects on clinical and functional outcomes and on health care expenditures, yet few individuals receive gold-standard insomnia treatment. The current article examines provider and patient outcomes associated with real-world implementation of Cognitive Behavioral Therapy for Insomnia (CBT-I), as part of a pilot initiative designed to establish initial capability for evidence-based insomnia treatment within one of the largest payor-provider systems in the United States. Provider training outcomes were assessed using the CBT-I Competency Rating Scale and self-report measures. Patient outcomes were assessed using the Insomnia Severity Index (ISI) and Patient Health Questionnaire-9. All clinicians (N = 11) achieved competency in CBT-I and reported large increases in knowledge and confidence related to insomnia and insomnia treatment. Clinicians also reported high intention to deliver CBT-I and significant improvements in overall job satisfaction following competency-based CBT-I training. Among all patients who initiated CBT-I (N = 48), mixed effects modeling demonstrated significant reduction in average ISI scores (12.57 to 5.88, SEs = 1.08-1.14). More than two-thirds of patients (68.8%) completed treatment. Among completers of this brief treatment, mean insomnia severity improvement was 71% (Hedges g = 1.56). Findings provide support for the feasibility and effectiveness of real-world CBT-I implementation, extending past findings to a private, payor-provider context. Patient and provider-level outcomes suggest the significant opportunity private systems may have in increasing the availability of gold-standard treatment for insomnia.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis

Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Integrated model of care for functional movement disorder: targeting brain, mind and body

Purpose To describe the therapy approaches and clinical outcomes of an integrated care model for patients with functional movement disorder (FMD). Materials and Methods A retrospective chart review was conducted for all treated individuals with a primary diagnosis of FMD between January 2020 and July 2022. Patients received time-limited integrated therapy (n = 21) (i.e., simultaneous therapy delivered by psychiatry, neurology and physiotherapy), physiotherapy (n = 18) or virtual physiotherapy alone (n = 9). Primary outcomes included the Simplified-Functional Movement Disorders Rating Scale (S-FMDRS) and Clinical Global Impression-Improvement scale (CGI-I) collected at baseline and post-intervention. Results Forty-eight patients completed treatment (42% male; mean age, 48.5 ± 16.6 years, median symptom duration 30 months). The most common presentations were gait disorder, tremor and mixed hyperkinetic FMD. Common comorbidities included pain and fatigue. Three-quarters of patients had a comorbid psychiatric diagnosis. There was a significant reduction in S-FMDRS score following therapy (71%, p < 0.0001) and 69% had “much” or “very much” improved on the CGI-I. There was no difference between therapy groups. Attendance rates were high for both in-person (94%) and virtual (97%) visits. Conclusions These findings support that a time-limited integrated model of care is feasible and effective in treating patients with FMD.

Comparison of efficacy and safety between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma.

The purpose of this study was to compare efficacy and side effects between oral propranolol combined with and without intralesional injection of lauromacrogol for infantile hemangioma (IH). This was a single center randomized controlled prospective study, all participants were firstly diagnosed with IH between August 2022 and January 2023 in our hospital and without any treatment before. Patients were randomized into two groups. PRO group: oral propranolol (2 mg/kg/day) continued for 6 months; PRO + LAU group: oral propranolol (2 mg/kg/day) for 6 months and intralesional injection of lauromacrogol for 2-4 times within 6 months. The dimensions, color, consistency, photographic documentation were well recorded based on Visual Analogue Scale (VAS) before and after starting treatment. According to the treatment response after 6 months, the results were classified into four levels: Grade 1, complete resolution achieved; Grade 2, with ≥50% reduction in size of IH; Grade 3, with <50% reduction in size of IH; Grade 4, no response or worsening of IH. A total of 67 patients were involved in the study (17 boys, 50 girls; mean age, 3.6 months, range, 1.1-7.2 months) and randomized to receive oral propranolol combined with or without intralesional injection of lauromacrogol (29 in PRO group, 38 in PRO + LAU group). All patients completed treatment. Eleven patients (37.9%) in PRO group were in Grade 1, 14 patients (48.3%) in Grade 2, 4 patients (13.8%) in Grade 3, compared with these in PRO + LAU group, 11 patients (28.9%) in Grade 1, 24 patients (63.2%) in Grade 2, and 3 patients (7.9%) in Grade 3. No patient was in Grade 4, and no severe side effects were observed in both group. In PRO group, it takes an average of 17.1 ± 5.4 weeks from the start of treatment to cure, and in PRO + LAU group, the average time is 13.7 ± 4.9 weeks. Oral propranolol with intralesional injection of lauromacrogol was a safety treatment strategy for IH. But it was not superior to oral propranolol in final cure rates (P = 0.45), moreover, it cannot certainly offer the benefits of shortening the duration of oral drug treatment (P = 0.24).

Progress Toward Tuberculosis Elimination and Tuberculosis Program Performance - National Tuberculosis Indicators Project, 2016-2022.

Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.