Greater Response Rate Research Articles

ADP101 multifood oral immunotherapy for food-allergic patients: Harmony phase 1/2 randomized clinical trial.

Oral immunotherapy is an established approach to desensitize the immune system in the context of allergic disease; however, the only currently approved product is for peanut allergy. ADP101 is a novel, pharmaceutical-grade, multifood oral immunotherapy in development to simultaneously treat single or multiple food allergies, containing allergenic proteins from 15 foods in equal parts by protein weight. The phase 1/2 Harmony trial (NCT04856865) evaluated efficacy and safety of ADP101 in participants with qualifying allergy to 1 to 5 foods in ADP101, defined as dose-limiting symptoms with a ≤100 mg challenge dose during double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomized to low-dose (1500 mg/d; 100 mg protein per food) or high-dose (4500 mg/d; 300 mg protein per food) ADP101, or matched placebo, with dose escalation followed by daily maintenance dosing over 40 weeks. The primary endpoint was the proportion of participants tolerating a ≥600 mg challenge dose of a single qualifying food without dose-limiting symptoms at the Week 40 Exit DBPCFC (ie, responders). In the primary analysis population (61 pediatric participants aged 4-17 years), a greater response rate was observed in both the high-dose ADP101 (55.0%) and low-dose ADP101 (38.1%) groups compared with pooled placebo (20.0%) (nominal P= .048, P= .306, respectively; adjusted for multiple comparisons, P= .097, P= .306, respectively). Desensitization to ≥2 foods was observed in individuals with multiple food allergies, as was desensitization at levels over 600 mg. ADP101-treated participants showed an overall reduction in skin-prick test reactivity, with an increase in maximum tolerated dose across the majority of foods tested. Adverse events were mostly mild or moderate, with no life-threatening events or deaths. The study did not meet its primary endpoint, but ADP101 demonstrated a favorable safety profile and increased the reactive threshold in DBPCFC in pediatric participants with single or multiple food allergies across multiple endpoints, warranting further clinical investigation.

Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review.

Propranolol, a nonselective β-blocker, is the first-line treatment for infantile hemangioma (IH). Topical timolol has recently been proposed as a novel IH treatment with fewer adverse effects. This study was conducted to compare the efficacy and safety of oral propranolol and topical timolol for treating IH. Studies were included after searching PubMed, Embase, Web of Science, and the Cochrane Library via the keywords of "propranolol", "timolol", "infantile hemangioma" and their synonyms. A meta-analysis with pooled odds ratios was performed using the fixed-effect model. Seven articles with 2071 patients were included in this meta-analysis. Compared with topical timolol, oral propranolol had a greater response rate (OR = 2.12, P < 0.001), but it was also associated with a greater risk of adverse events (OR = 2.31, P < 0.001). For superficial IH, timolol demonstrated similar efficacy to propranolol (OR = 1.28, P = 0.34) but with fewer adverse events (OR = 2.30, P = 0.001). Additionally, compared with topical timolol, propranolol at a dosage of 2mg/kg/d had a better response rate (OR = 2.62, P < 0.001), whereas the 1.0∼1.5mg/kg/d propranolol group showed no significant difference (OR = 1.34, P = 0.38). Oral propranolol presents superior therapeutic efficacy in the treatment of IH compared to topical timolol. However, topical timolol can serve as an alternative to oral propranolol for treating superficial IH, providing similar efficacy with fewer adverse effects. Additionally, propranolol at a dosage of 2mg/kg/d offers greater efficacy with a comparable safety profile, whereas the 1.0∼1.5mg/kg/d propranolol dosage shows no significant difference in efficacy compared to timolol but is associated with more adverse events. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024603724, identifier CRD42024603724.

Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy.

Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC. We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups. Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0months vs. 3.0months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy. Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis

AbstractThe ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non–transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542.

Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study.

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1year and 9 treated for > 3years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028). Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: • Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. •Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate.

Abstract C126: Communicating breast cancer risk to Spanish-speaking Hispanic women

Abstract INTRODUCTION Disparities in breast cancer (BC) screening are observed between Hispanic and non-Hispanic White women and stronger amongst Hispanic women with under- and uninsured statuses.1-2 Risk-based screening has been recommended by professional societies, including American Cancer Society, starting at age 30 and may be an important strategy for reducing disparities.3 The purpose of the study was to characterize whether women had been told their personal risk of BC and to identify differences in characteristics of patients informed of their personal risk. METHODS This is a cross-sectional analysis of data from a supplemental self-reported survey to an NIH-funded randomized trial conducted at a large Federally Qualified Health Center (FQHC) in Arizona (R01 MD09682-05). The survey was sent to a randomized 600 of the 1,356 participants. Between November 2022 and April 2023, 177 women completed the survey (response rate 29.5%). Participants were asked if a doctor or other healthcare provider had ever talked to them about their personal risk for BC. Differences between those who recalled being told their personal risk for BC and those who did not were assessed using Fisher exact test. RESULTS Overall, 66.3% were 50 years or older, 81.8% who speak primarily Spanish, and 64.8% of respondents had less than a high school education. Also, 22.4% reported a family history of BC, 27.4% have been previously recalled for additional imaging, 10.8% have had a history of prior breast biopsy, 59.9% stated having a regular provider, and 53.1% were found to have dense breast category C or D at screening visit. 40% did not report having a regular doctor although all participants received care at an FQHC. 30.5% of respondents stated that a healthcare professional had ever talked to them about their personal risk for BC. There was a trend toward women with a main doctor being more likely to recall being told their personal risk for BC as compared to those without a main doctor (38.5% vs 22.5%, p=0.06). CONCLUSIONS In this cohort of primarily Spanish-speaking Hispanic women who have had mammography screening and written report of their breast density, about a third of respondents recall being informed of their personal BC risk. These observations need to be confirmed in a larger population with greater response rate, but these results suggest that there is a cohort of patients who need different approaches for conveying risk. REFERENCES 1. Jadav, S., Rajan, S. S., Abughosh, S., &amp; Sansgiry, S. S. (2015). The Role of Socioeconomic Status and Health Care Access in Breast Cancer Screening Compliance Among Hispanics. Journal of Public Health Management and Practice, 21(5), 467–476. https://www.jstor.org/stable/48517175 2. American Cancer Society. (2017). Breast cancer facts &amp; figures 2017-2018. Atlanta, GA: American Cancer Society, Inc. 3. ACS Breast Cancer Screening Guidelines. (2022, January 14). https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.htm Citation Format: Jhenitza P. Raygoza Tapia, Sarah M. Jenkins, Jennifer L. Ridgeway, Aaron D. Norman, Crystal R. Gonzalez, Valentina Hernandez, Bhavika K. Patel, Celine M. Vachon, Jessica D. Austin. Communicating breast cancer risk to Spanish-speaking Hispanic women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C126.

Efficacy of Guselkumab on Axial-Related Symptoms Through up to 2 Years in Adults with Active Psoriatic Arthritis in the Phase 3, Randomized, Placebo-Controlled DISCOVER-2 Study.

Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week0, week4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6-1.7 for ASDAS; 49-54% achieved BASDAI50 and 39% achieved ASDAS major improvement at week 100. Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Clinicaltrials.gov NCT03158285.

Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis

BackgroundATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens.MethodsA systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses.ResultsWe obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses’ findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease.ConclusionIFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.

The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: A systematic review and meta-analysis.

A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache. Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the 'meta' package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences. Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (-0.502 standard deviations [-0.945, -0.058]), headache frequency (-2.830 days/month [-4.082, -1.578]), daily headache duration (-0.965 [-1.860, -0.069]) and the frequency of acute pain medication use (-2.200 days/month [-3.485, -0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient. Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted. Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616).

Do web-based follow-up surveys have a better response rate than traditional paper-based questionnaires following outpatient arthroscopic rotator cuff repair? A randomized controlled trial

IntroductionConsidering the extensive use of smartphones in current societies, web-based applications could be considered as a new option for patient follow-up in surgery. By means of such tool, automated and periodic questionnaires could improve the rigor, accuracy and the comprehensiveness of postoperative monitoring, as well as early detection of complications, especially in the current context of evolving ambulatory surgery. HypothesisThe web-based surveys would improve the quality of immediate postoperative monitoring. Material and methodsFor 7 months, we included all patients who underwent outpatient arthroscopic rotator cuff repair. After preoperative randomization, each patient was asked postoperatively to complete either paper-based forms or digital questionnaires via a website (Orthense.com®, Digikare Inc. Blagnac, France). Both media (i.e. paper and digital) followed the same postoperative agenda (i.e., D+3, D+14, D+28, D+45, D+90) and had the same content, including pain and discomfort assessments, functional scores (i.e. Shoulder subjective value, simple shoulder test and auto-constant scores). The main objective was to investigate the quality of postoperative follow-up after outpatient arthroscopic rotator cuff surgery, using either printed questionnaires or web-based surveys. The hypothesis was that using a web-based survey would result in greater response rates and increased patient satisfaction regarding follow-up. Primary outcomes were questionnaire response rates at D+45 and D+90, while secondary outcomes were overall response rates, patient recommendation for the monitoring medium and overall patient satisfaction regarding their follow-up using the net promoter score (NPS). ResultsAmong the 59 consecutive patients who were included, there were 27 females and 26 males with a mean age of 57±10.2 years; 27 patients completed the web-based survey (Group A) and 26 patients answered paper-based questionnaires (Group B). Regarding the D+45 questionnaire, response rates were 85.2% (n=23) in group A and 42.3% (n=11) in group B (p=.005); a similar significant difference was observed regarding the D+90 questionnaire, with response rates of 70.4% and 34.6%, respectively (p=.027). The mean NPS for the survey was 10 in Group A and 8.29 in Group B (p=.016). Overall, satisfaction regarding postoperative care did not differ between the two groups. DiscussionCompared to traditional paper-based forms, web-based surveys appear to increase patient adherence to short-term postoperative monitoring. If these findings were to be confirmed in long-term follow-up, such straightforward and cost-effective tool could be of great use in clinical care and research. Level of evidenceI; Randomized controlled clinical trial.

Stimuli-responsive heterojunctions based photo-electrocatalytic membrane reactors for reactive filtration of persistent organic pollutants

The design of semiconducting metal oxide heterojunctions is promising to overcome conventional limitations associated to photocatalysis or electrocatalysis, such as fast recombination of electron-hole pairs and poor long-term stability leading to low catalytic performance. A route to tackle this issue is to design catalysts at the atomic levels by arranging order and controlling nanoscale interfaces to yield catalytic materials with greater response rates and stability to dissolution or corrosion. The present study focuses on the formation of such nanoscale heterojunctions between TiO2 and ZnO via atomic layer deposition across conductive and porous stainless-steel substrates to develop enhanced photo-electro-responsive catalytic membrane reactors. The heterojunction nano-sheet based structures produced higher density of electron and hole pairs and offered efficient separation of charges, longer lifetime of photo-generated electrons compared to single metal oxides, resulting in enhanced photocurrent efficiency. The tailoring of both the nanoscale dimensions of the metal oxide layers and the stacking of these inorganic nano-sheets led to the development of multi-heterojunctions, of a few tens of nanometres, deposited across conductive porous substrates. The high electron mobility across the heterojunction nano-sheets increased the oxygen evolution potential from 1.4 to 1.7 eV, leading to enhanced electrochemical reactions, as well as offered photocurrent densities 2–3 times higher than pristine single metal oxide membranes. The formation of type II heterojunction structures between TiO2 and ZnO leads to band alignment at the interface, yielding an efficient charge separation mechanism and high catalytic performance. A prototype of novel cross-flow filtration module was designed in this study to support the coupling of photo-electrocatalysis on the membrane surface and simultaneous pressure driven membrane processes. The designed 3D printed modules demonstrated highly enhanced degradation of several persistent organic pollutants, leading to reactivity up to 75 × 10−3 min−1 up to 500 % greater compared to single metal oxides generated with the same conditions. The intimate and synergistic interactions across the stacked metal oxide nano-sheets enabled high catalytic efficiency and stability, opening new avenues stimuli-responsive membranes scale up and implementation in wastewater remediation and compact reactors design, where sieving and reactivity are of prime importance.

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

Background and purposeIntravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE.MethodsThis was a retrospective study in one referral center of all consecutive VPA‐naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics.ResultsAmong 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7–58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg.ConclusionsA high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25–30 mg/kg appears adequate in SE.

Responses to Ixekizumab in Male and Female Patients with Psoriatic Arthritis: Results from Two Randomized, Phase 3 Clinical Trials.

IntroductionDifferences in psoriatic arthritis (PsA) treatment response between sexes for ixekizumab, an interleukin-17A antagonist, are largely unexplored. This analysis used data from randomized clinical trials (RCTs) evaluating ixekizumab to study differences in treatment response between male and female patients with PsA.MethodsWe used pooled data from patients enrolled in SPIRIT-P1 and SPIRIT-P2 (NCT01695239 and NCT02349295, respectively), phase 3 RCTs evaluating ixekizumab every 4 and 2 weeks in patients with active PsA. Subgroups of patients were defined by sex (male, female). Efficacy was measured by the proportion of male and female patients achieving American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70), minimal disease activity or very low disease activity (MDA/VLDA), and Disease Activity Index for Psoriatic Arthritis (DAPSA) scores representing low disease activity (LDA) or remission through week 156. Changes from baseline in components of the above measures were also assessed through week 156.ResultsCompared to male patients at baseline, female patients were older, had higher body mass index and lower C-reactive protein levels, and had worse tender joint count, Health Assessment Questionnaire Disability Index, and Leeds Enthesitis Index scores. Through week 156, female patients in all treatment arms had lower response rates than male patients in all analyzed composite measures (ACR20/50/70; MDA/VLDA; DAPSA LDA/remission), with significant differences observed at multiple timepoints in both ixekizumab treatment arms. Female patients also had smaller numeric changes from baseline in the composite measures’ individual components.ConclusionCompared to female patients, male patients had greater response rates in ACR20/50/70, MDA/VLDA, and DAPSA LDA/remission and numerically larger improvements in these measures’ individual components, although clinical significance is unclear. Continued efforts to understand sex differences in treatment response may provide insights that can help optimize clinical decision making.Trial registrationClinicalTrials.gov identifiers, NCT01695239 and NCT02349295.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00445-w.

Early Biologic Initiation After Chronic Pouch Inflammation Diagnosis Does Not Impact Clinical Outcomes

Approximately 20% of patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) develop chronic pouch inflammation (CPI).1 Given the involvement of the small bowel in CPI, there is no consensus on whether it should be managed more like UC or Crohn's disease (CD). Despite limited evidence, biologics are often used for CPI with clinical response rates of 20%-60% with adalimumab and infliximab, 50%-80% with ustekinumab, and 30%-70% with vedolizumab.2,3 Earlier biologic therapy has been associated with greater rates of response and favorable long-term outcomes in patients with CD, however not UC.4-7 The impact of earlier initiation of biologic therapy on CPI clinical outcomes has not been elucidated. The aim of this study was to assess whether timing of biologic initiation relative to CPI diagnosis impacts clinical and endoscopic remission.

Association between immune-related adverse event timing and treatment outcomes

ABSTRACT The timing of immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI) is highly variable. Although the development of irAE has been associated with ICI clinical benefit, how irAE timing influences this association is unknown. We analyzed two independent cohorts including 154 patients with non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors at a single institution (UTSW cohort) and a multi-center cohort of 433 patients with NSCLC who received second-line anti-PD-1/PD-L1 therapy (Global cohort) to assess the association between ICI outcomes and irAE timing. In both cohorts, late-onset irAE occurring more than 3 months after ICI initiation compared to irAE occurring earlier were associated with greater rates of radiographic response (UTSW cohort, 41% versus 28%, P = .26; Global cohort, 60% versus 35%, P = .02), longer progression-free (UTSW cohort, 13.7 versus 5.6 months, P < .01; Global cohort, not reached versus 6.0 months, P < .01) and overall survival (UTSW cohort, 30.9 versus 14.6 months, P < .01; Global cohort, not reached versus 10.6 months, P < .01). Modified landmark analysis at 6 months confirmed an overall survival difference between early- and late-onset irAE. Late-onset irAE was similarly associated with greater response rates and prolonged survival in a cohort of 130 patients with non-NSCLC malignancies, suggesting a conserved association across tumor types. The favorable association between irAE and ICI clinical outcomes may be attributed to later-onset events, which is not wholly explained by survivor bias. These results allude to a distinct biology between early- and late-onset irAE and may guide clinician expectations and thresholds for continuing or modifying immunotherapy.

2020 Association for Applied and Clinical Sociology Membership Survey

The Association for Applied and Clinical Sociology (AACS) was formed in 2005 by the merger of the Society for Applied Sociology and the Sociological Practice Association giving name recognition to both applied and clinical sociology, and a professional home for all sociological practitioners. In an effort to provide greater benefit and value to members, and to better meet the needs of its members, the AACS conducted a membership survey. On October 9, 2020, a membership survey was sent to AACS members to gather data. While the current survey results could have benefited from a greater response rate, the data gathered provides some degree of insight to members’ characteristics and attitudes toward the AACS. It is recommended that the AACS consider conducting future membership studies periodically to determine how to better meet member needs, and to estimate the value of AACS to its members.

Customer participation in service innovation using SNS smartphone apps: an investigation of the Indian hotel service industry

PurposeExisting research lacks a comprehensive understanding of the individual factors that may transform an “ordinary” customer into an active participator in the service innovation process and/or the situational factors that determine a customer's participation in any stage of the service innovation process. The purpose of this paper is to fill these research gaps by developing and validating a conceptual framework on CPSIB in the Indian hotel industry by using smartphones to access SNS apps.Design/methodology/approachA cross-sectional survey design method was used in this study to collect representative samples with greater response rates. The target population included in this study were hotel guests of all of the star category hotels in New Delhi who had earlier experiences of staying in star category hotels. Structured questionnaire was formulated, which was later pre-tested to confirm its reliability and validity. Out of 400 questionnaires, 348 usable responses were obtained.FindingsThis research examines CPSIB in the Indian hotel industry using SNS smartphone apps. It confirms that user innovativeness and perceived trust in the service provider determine customers' participative service innovation behavior, which further results in positive adoption intention via SNS smartphone apps.Research limitations/implicationsThis research provides valuable insights into the hotel industry, specifically in the context of India. However, it has a few limitations that must be taken into account when generalizing its results.Practical implicationsFirst, investigating the key antecedents and consequences of CPSIB has important implications for marketing practitioners. Moreover, it was observed that hotel guests with higher innovativeness and trust in the service provider would show positive participative service innovation behavior toward innovating new services along with the hotel service providers, which may result in a positive adoption intention toward the newly developed services. Second, hoteliers should integrate hotel guests into hotel service innovation via the use of SNS smartphone apps.Social implicationsThis research conceptualizes that user innovativeness is a driving factor for CPSIB that may further generate a positive adoption intention toward newly developed services.Originality/valueTo the best of the authors’ knowledge, only a very few studies have tested the interrelationships between individual factors and customer participation behavior in the mobile technology-mediated service ecosystem simultaneously. Furthermore, research examining the individual and situational factors influencing CPSIB and adoption intention towards newly developed services using SNS smartphone apps is still in a nascent stage.

Immune Checkpoint Inhibitor in First-Line Treatment of Metastatic Renal Cell Carcinoma: A Review of Current Evidence and Future Directions

The incidence of renal cell carcinoma (RCC) is rising and metastatic RCC carries a very poor prognosis. The treatment paradigm for metastatic RCC has shifted dramatically in the last decade with multi-targeted tyrosine kinase inhibitors (TKI) previously used as first-line treatment but its utility is limited by short-lived efficacy and rapid disease progression. The dysregulation of immune cells in the tumour microenvironment contributes to unregulated growth of RCC. Thus, the use of immune checkpoint inhibitors has become first-line treatment for metastatic RCC and has offered dramatic improvement in clinical benefit and survival. Treatment with immune checkpoint inhibitor in combination with TKI appears to be promising in offering even greater response rates. The treatment for metastatic RCC continues to evolve and ongoing advances with new targeted agents and biomarkers are needed to continue to improve prognosis in the future.

Review and Meta-analysis on the Impact of the ADRA2A Variant rs1800544 on Methylphenidate Outcomes in Attention-Deficit/Hyperactivity Disorder

BackgroundMethylphenidate is among the most prescribed medications for treating attention-deficit/hyperactivity disorder (ADHD). However, nearly half of pediatric patients with ADHD do not respond to methylphenidate treatment. Pharmacogenetic testing can aid in identifying patients for whom methylphenidate is unlikely to be safe or effective, leading to improved methylphenidate outcomes and increased use of alternative treatment options for ADHD. This article aimed to summarize findings from studies of the ADRA2A gene variant, rs1800544, and its association with methylphenidate outcomes in ADHD. MethodsWe systematically reviewed and meta-analyzed available literature on the impact of rs1800544 on methylphenidate outcomes in ADHD. ResultsFourteen studies met inclusion criteria for review, 9 of which were eligible for meta-analysis. The included studies compared methylphenidate outcomes in patients with ADHD categorized by rs1800544 genotype. G-allele carriers experienced significantly greater improvements in ADHD symptom scores (Swanson, Nolan, and Pelham Version-IV Scale or ADHD Rating Scale-IV) relative to noncarriers (odds ratio 3.08, 95% confidence interval 1.71–5.56, p = .0002) and greater response rates as measured by a ≥50% improvement in symptom scores (odds ratio 2.68, 95% confidence interval 1.23–5.82, p = .01); no significant difference in response rate as measured by Clinical Global Impressions score ≤2 was found. Stouffer’s z-score method showed significant improvement across all methylphenidate outcomes in G-allele carriers relative to noncarriers (z = 3.03, p = .002). ConclusionsThese findings suggest that carriers of rs1800544 may have improved ADHD outcomes following methylphenidate treatment. However, the extent to which these improvements are clinically impactful remain unclear. Additional studies are required to determine if rs1800544 carrier status should influence clinical recommendations for treatment of ADHD symptoms.

Abstract CT174: Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma

Abstract BACKGROUND Trastuzumab is a monoclonal antibody targeting HER2 standardly administered with multi-agent chemotherapeutics in the 20-30% of metastatic gastric and esophageal adenocarcinomas that overexpress HER2. Preclinical data shows that trastuzumab requires a functional adaptive immune system for efficacy, suggesting synergy of trastuzumab combined with immune checkpoint inhibitors. Moreover, cytotoxic chemotherapy facilitates tumor antigen presentation, and the combination of anti-PD-1 therapy and chemotherapy was recently found to improve progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone in HER2-negative metastatic gastric cancer. We hypothesized that the addition of the anti-PD-L1 antibody avelumab to trastuzumab and FOLFOX chemotherapy would result in a greater response rate than expected with trastuzumab + FOLFOX alone in HER2-amplified gastroesophageal cancer. METHODS HCRN GI17-319 was a multicenter, single-arm, phase II clinical trial with a prespecified 6-subject safety run-in of avelumab, trastuzumab, and mFOLFOX6 in previously untreated, metastatic, HER2-amplified gastric and esophageal adenocarcinomas (NCT03783936). The primary endpoint was best response rate within the first 24 weeks. Secondary endpoints included PFS and adverse events (AEs). Subjects received 9 cycles of induction avelumab, trastuzumab, and mFOLFOX6 every 14 days, followed by maintenance avelumab + trastuzumab every 14 days. The study was initially designed as a Simon's two stage trial, but enrollment was stopped after the 18-subject first stage for reasons unrelated to safety or efficacy. RESULTS A total of 18 subjects, including the 6-subject safety run-in, were enrolled 4/2019-8/2020. The 24-week response rate was 11/18 (61%; 95% CI 39-84%), including one complete response. The confirmed overall response rate is 7/18 (39%), but 3 unconfirmed responders are still on treatment. With 11 progression events, median PFS was 8.0 mo (95% CI 4.2-11.9). The regimen was well tolerated, with most common treatment-related grade 3-4 AEs of decreased neutrophil count (28%), decreased platelet count (11%), anemia (11%), and hypokalemia (11%). CONCLUSIONS The combination of avelumab, trastuzumab, and FOLFOX chemotherapy demonstrated evidence of activity, and response rate and median PFS compared favorably to results expected with trastuzumab + chemotherapy from historical data. These outcomes corroborate with results from prior small studies of chemotherapy, trastuzumab, and immune checkpoint inhibitors in patients with HER2-amplified metastatic gastroesophageal adenocarcinoma and demonstrate the exciting potential for addition of immune checkpoint inhibitors in this setting. Correlative studies from tumor specimens and peripheral blood collected on study are in progress. Citation Format: Michael S. Lee, Joseph Chao, Mary F. Mulcahy, Pashtoon M. Kasi, Angela T. Alistar, Sarbajit Mukherjee, Mehmet Akce, Dominic T. Moore, Cheryl A. Carlson, Autumn J. McRee. Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT174.