Advances in Therapy最新文献

{"title":"Clinical Remission is Achievable for Adult Patients with Severe Asthma Receiving Mepolizumab: A European Retrospective Chart Review.","authors":"Stephen G Noorduyn, Samantha N Valliant, Steven Gould, Louise H Yu, Rose Chang, Rui Song, Megan Pinaire, Leili Young-Xu, Mei S Duh, Stefano Aliberti","doi":"10.1007/s12325-026-03692-3","DOIUrl":"https://doi.org/10.1007/s12325-026-03692-3","url":null,"abstract":"<p><strong>Introduction: </strong>The introduction of precision therapy in severe asthma is shifting treatment goals from asthma control towards the more ambitious target of clinical remission. This study evaluated clinical remission in patients with severe asthma receiving mepolizumab in Europe.</p><p><strong>Methods: </strong>A retrospective, physician panel-based chart review was conducted based on anonymised data from patients who initiated mepolizumab in Italy, Germany, and France from 30 June 2017 to 30 June 2022. Primary outcome was clinical remission at Year 1 post-initiation, defined as the absence of severe or clinically significant asthma exacerbations, no maintenance oral corticosteroid use in Month 12, and an Asthma Control Test score ≥ 20, plus either lung function stabilisation (no worsening of forced expiratory volume in 1 s [FEV₁] from baseline) or lung function optimisation (FEV₁ ≥ 80% predicted). Individual components of clinical remission were compared before versus after mepolizumab initiation, and clinical remission at Year 2 was also assessed.</p><p><strong>Results: </strong>Data from 308 patients were included by 117 physicians. Clinical remission based on lung function stabilisation was achieved by 37.8% of patients (101/267) at Year 1 and 58.7% (108/184) at Year 2. Remission based on lung function optimisation was achieved by 18.8% (58/308) at Year 1 and 28.6% (55/192) at Year 2. Regardless of the lung function definition used, ≥ 90% of patients who achieved remission at Year 1 maintained it until Year 2 (among those with evaluable data). Individual components of clinical remission, including FEV₁ ≥ 80% predicted, showed significant improvements at 12 months compared with baseline (all p < 0.001).</p><p><strong>Conclusion: </strong>This real-world study demonstrates that clinical remission is an ambitious and achievable treatment goal for patients with severe asthma treated with mepolizumab in Europe. Graphical abstract available for this article.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intraoperative Transcutaneous Electrical Acupoint Stimulation Attenuates Postoperative Mechanical Pain Sensitization and Visceral Pain After Elective Cesarean Delivery: A Randomized Controlled Trial.","authors":"You Yang, Qiuxia Deng, Xiaodong Zhu, Meiying Hu, Jing Chen, Guangyou Duan, Rong Liao, Maojun Li","doi":"10.1007/s12325-026-03746-6","DOIUrl":"https://doi.org/10.1007/s12325-026-03746-6","url":null,"abstract":"<p><strong>Introduction: </strong>Postoperative pain after cesarean delivery remains prevalent despite multimodal analgesia. This randomized controlled trial evaluated whether continuous intraoperative transcutaneous electrical acupoint stimulation (TEAS) attenuates postoperative mechanical pain sensitization and improves clinical pain outcomes.</p><p><strong>Methods: </strong>Eighty parturients undergoing elective cesarean delivery under neuraxial anesthesia were randomized 1:1 to TEAS (PC6 and LI4; from 30 min before incision until 10 min after closure) or sham control. The primary outcome was mechanical pain sensitization, quantified by the 30-min postoperative-to-baseline pressure pain threshold (PPT) ratio. Secondary outcomes included PPT and pain tolerance threshold (PTO) at 30 min and 24 h, threshold change ratios, postoperative pain scores, patient-controlled intravenous analgesia (PCIA) use, adverse events, and hospital stay.</p><p><strong>Results: </strong>Seventy-nine participants were analyzed. TEAS significantly increased the 30-min PPT ratio compared with control (mean difference 0.208, 95% CI 0.057-0.359; P = 0.008). PPT and PTO remained higher in the TEAS group at 24 h, and all four threshold change ratios favored TEAS (all P < 0.05). Clinically, TEAS reduced uterine cramping pain scores at 6 h and 24 h and lowered the incidence of severe visceral pain (15.38% vs. 40.00%; in the multivariable model, the adjusted OR was 0.26 [95% CI 0.08-0.73; P = 0.005]). Hospital stay was shorter in the TEAS group (median 6.00 vs. 7.00 days; P = 0.010). No intervention-related adverse events were observed. Static and dynamic incisional pain outcomes and cumulative analgesic consumption did not differ significantly between groups.</p><p><strong>Conclusion: </strong>Continuous intraoperative TEAS was associated with attenuated postoperative mechanical pain sensitization and reduced visceral pain burden after elective cesarean delivery. Its effects were less evident for incision-related pain and opioid consumption. TEAS may serve as a safe, valuable non-pharmacological adjunct to multimodal post-cesarean analgesia. Apart from the primary outcome, secondary findings (including visceral pain, hospital stay, and threshold change ratios) were not adjusted for multiple comparisons and should be regarded as exploratory and hypothesis-generating. Graphical Abstract available for this article.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry (ChiCTR2200058422).</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperkalemia Management in the US Cohort of the Prospective, Observational, Real-World TRACK Study.","authors":"Elvira O Gosmanova, Javed Butler, Johanna P Contreras, Linda F Fried, Amarnath Kathresal, Wolfgang C Winkelmayer, Hungta Chen, Pooja Desai, Mark Sanford, Eric Wittbrodt, Judith Hsia","doi":"10.1007/s12325-026-03738-6","DOIUrl":"https://doi.org/10.1007/s12325-026-03738-6","url":null,"abstract":"<p><strong>Introduction: </strong>The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study demonstrated that clinical practice guidelines for hyperkalemia are inconsistently implemented and a conservative approach to management is often preferred. We report additional analyses focusing on routine clinical practice in the USA.</p><p><strong>Methods: </strong>TRACK was an observational prospective cohort study (July 2022-December 2024) including adults in the USA with a recent index hyperkalemia episode (serum potassium [K⁺] > 5.0 mmol/L ≤ 21 days of enrollment). Primary and secondary data were obtained from participants, their respective healthcare professionals (HCPs), and medical records. Clinical characteristics, hyperkalemia management decisions and rationales, and treatment outcomes over 12 months were evaluated.</p><p><strong>Results: </strong>The final cohort included 229 participants, of whom 66.4% and 30.6% had mild (serum K⁺ > 5.0 and ≤ 5.5 mmol/L) and moderate (serum K⁺ > 5.5 and ≤ 6.5 mmol/L) hyperkalemia at baseline, respectively. Only 51.5% of participants received renin-angiotensin-aldosterone system inhibitors (RAASis) at baseline, despite 95.2% having concomitant chronic kidney disease (CKD), heart failure (HF), or both. HCP-reported hyperkalemia management approaches at baseline and month 12, respectively, included monitoring serum K⁺ levels (79.5%; 79.3%), a low-K⁺ diet (73.4%; 72.6%), continuation of RAASi therapy (49.8%; 49.0%), and prescription of a K⁺ binder (28.4%; 15.4%). The most commonly reported rationales for management decisions at baseline and month 12, respectively, were ease of treatment (47.3%; 55.3%), alignment with CKD treatment guidelines (46.4%; 36.7%), and safety (20.7%; 21.1%). Over 12 months, 82.5% of participants achieved K⁺ normalization (≤ 5.0 mmol/L) at any timepoint. Hyperkalemia recurrence was reported in 32.9% of participants at month 6, 34.2% at month 9, and 28.0% at month 12.</p><p><strong>Conclusions: </strong>This study shows that conservative hyperkalemia management and hyperkalemia recurrence are common in routine practice in the USA. Additionally, among individuals with hyperkalemia at baseline, only half of eligible patients with CKD and/or HF were prescribed RAASi therapy. These data highlight the need for effective strategies to treat hyperkalemia and to improve implementation of guideline-directed therapy for CKD and HF. Graphical Abstract available for this article.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05408039.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRIDGE-2M: Optimizing Bridging Therapy Prior to CAR-T Therapy in Multiple Myeloma: A Modified Double-Blind Delphi Panel of US Physicians.","authors":"Rahul Banerjee, Hamza Hashmi, Preet M Chaudhary, Shebli Atrash, Kimberly Green, Sabyasachi Ghosh, Todd Bixby, Denise De Wiest, Matthew Perciavalle, David H Vesole, Forat Lutfi, Waqas Jehangir, Gurbakhash Kaur, Adeel M Khan, Rahma Warsame, Ashwathi Puravankara Menon, Mark A Price, Guru Subramanian Guru Murthy, Danai Dima, Brian J Carney, Zaina P Qureshi, Saurabh Chhabra","doi":"10.1007/s12325-026-03737-7","DOIUrl":"10.1007/s12325-026-03737-7","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to achieve consensus on optimal bridging therapy (BT) selection for patients with relapsed/refractory multiple myeloma (RRMM) undergoing chimeric antigen receptor T-cell (CAR-T) therapy.</p><p><strong>Methods: </strong>We conducted a double-blind, three-round modified Delphi panel among U.S.-based hematologist-oncologists/hematologists using CAR-T therapy for RRMM.</p><p><strong>Results: </strong>Panelists (N = 15; all managing -60-100 patients with RRMM within the past year; > 5 years of practice: 86.7%) reached consensus on key attributes influencing BT selection (disease burden, aggressive disease, performance status, comorbidities, line of therapy, age, frailty). Unique patient attributes were linked to clinical objectives (≥ 65 years or frailty: disease stabilization [71% consensus]; poor performance status: end-organ function preservation; comorbidities: functional preservation; high disease burden: preventing clinical decline; aggressive disease: cytoreduction [all 100% consensus]). Goals of BT were to decrease disease burden and promote CAR-T efficacy and safety (100% consensus). While talquetamab was preferred for bridging in later lines (66.7%), 73.3% would consider earlier-line use if approved.</p><p><strong>Conclusion: </strong>This study synthesized expert physician perspectives to develop a consensus-based framework to optimize BT selection, linking five key patient attributes to clinical objectives, with goals extending beyond disease stabilization to enhancing CAR-T efficacy and safety. Graphical abstract available for this article 10.6084/m9.figshare.33016328.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative Complications Associated with Advanced Therapies in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.","authors":"Mohammed Nabil Quraishi, Maryam A AlAhmad, Alaa El-Hussuna, Badr Al-Bawardy","doi":"10.1007/s12325-026-03748-4","DOIUrl":"https://doi.org/10.1007/s12325-026-03748-4","url":null,"abstract":"<p><strong>Introduction: </strong>Whether preoperative advanced therapy increases postoperative complications in inflammatory bowel disease (IBD) is contested. We conducted a cross-class systematic review distinguishing crude from confounding-adjusted estimates.</p><p><strong>Methods: </strong>Five databases were searched to May 2026 for studies of patients with IBD undergoing abdominal surgery. Random-effects meta-analysis estimated comparative odds ratios (ORs) with 95% confidence intervals (CIs) versus unexposed patients across 13 pre-specified outcomes. Confounding-adjusted estimates were pooled separately by inverse-variance, contrasted with crude, meta-regressed on adjustment quality, and rated by GRADE.</p><p><strong>Results: </strong>Ninety-four publications were included. Across the pooled comparisons, advanced therapies were not associated with a uniform excess of postoperative complications; an isolated deep vein thrombosis signal (OR 2.62) most plausibly reflects disease-severity confounding. Crude anti-tumour necrosis factor (anti-TNF) exposure was associated with higher overall complications (OR 1.14, 95% CI 1.02-1.28) and, most reproducibly, intra-abdominal abscess (1.18, 1.01-1.39; 1.34 good-quality); infliximab with sepsis (2.38, 1.30-4.38). Infectious complications, SSI and anastomotic leak were non-significant, and signals were confined to Crohn's disease. After confounding adjustment, anti-TNF odds remained elevated (overall 1.53, 1.12-2.08, k = 18; infectious 1.51, 1.18-1.92) but were heterogeneous, attenuated with adjustment depth to non-significance in the most-adjusted stratum, and null in the only study confirming exposure by measured serum drug levels rather than a preoperative calendar window (infection 1.05). Vedolizumab showed no complication increase but higher readmission (1.70) and reoperation (1.65), consistent with channelling bias.</p><p><strong>Conclusions: </strong>Although there was a signal for association of advanced-therapy with certain complications, the signal is small, heterogeneous, of very low certainty, and absent in drug-level-confirmed evidence. These data are not robust evidence of independent harm and do not justify routine preoperative discontinuation or delay of necessary surgery.</p><p><strong>Trial registration: </strong>This systematic review was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261323118).</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Assessment of Healthcare Resource Utilization-Defined Manic and Depressive Events Among Patients with Bipolar I Disorder Treated with Cariprazine Versus Aripiprazole.","authors":"Roger S McIntyre, Mousam Parikh, Enrico Zanardo, François Laliberté, Huy-Binh Nguyen, Eric J Christopher, Lauren C Aronin, Kaixin Zhang, Sophie Ma, Jamie Ta","doi":"10.1007/s12325-026-03654-9","DOIUrl":"https://doi.org/10.1007/s12325-026-03654-9","url":null,"abstract":"<p><strong>Introduction: </strong>Atypical antipsychotics (AAs) are first-line treatments for bipolar I disorder (BP-I). While cariprazine is approved in the US for the treatment of both BP-I manic/mixed and depressive episodes, most other AAs are only approved for one affective pole but are utilized across the disease spectrum. For example, aripiprazole is only approved for BP-I manic/mixed episodes. This real-world analysis compared the rates of healthcare resource utilization (HRU)-defined manic and depressive events among patients treated with cariprazine versus aripiprazole.</p><p><strong>Methods: </strong>A retrospective observational cohort study was conducted using IQVIA^® PharMetrics^® Plus Database (5/28/2018-6/30/2022). Adults diagnosed with BP-I with ≥ 2 dispensings for cariprazine or aripiprazole were included. Cohorts were balanced via inverse probability of treatment weighting. Manic and depressive events were identified using a claims-based algorithm and reported per person-year (PPY) by setting of care [inpatient, emergency department (ED), and outpatient] and overall (any setting). Manic and depressive events during the ≥ 3-month on-treatment period were compared between cohorts via rate ratios (RRs) with P values and 95% CIs generated using nonparametric bootstrap procedures.</p><p><strong>Results: </strong>The cariprazine cohort included 2530 patients with 604 manic and 884 depressive overall events, while the aripiprazole cohort included 7057 patients with 2301 manic and 2958 depressive overall events. The overall rate of HRU-defined manic events PPY was 37% lower in the cariprazine versus aripiprazole cohort [RR (95% CI): 0.63 (0.43, 0.94); P < .05]. Rates of outpatient-defined manic events were also significantly lower for cariprazine versus aripiprazole [0.62 (0.39, 0.94); P < .05], whereas inpatient and ED-defined manic events were similar. The overall rate of HRU-defined depressive events PPY was 28% lower for cariprazine than aripiprazole [0.72 (0.59, 0.90); P < .001], which was driven by the significantly lower rate of outpatient-defined events for cariprazine [0.72 (0.58, 0.89); P < .001]; inpatient- and ED-defined events were similar.</p><p><strong>Conclusion: </strong>In this real-world analysis, overall rates of HRU-defined manic and depressive events were significantly lower for cariprazine versus aripiprazole, demonstrating the relative real-world value of cariprazine versus aripiprazole, and underscoring the potential HRU benefits of cariprazine's full-spectrum efficacy.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Costs of Comorbidities and Complications Associated with Type 2 Diabetes: A Retrospective, Cohort Study.","authors":"Kendra A Terrell, Maureen J Lage, William J Valentine, Jim S Paik, Kristina S Boye","doi":"10.1007/s12325-026-03753-7","DOIUrl":"https://doi.org/10.1007/s12325-026-03753-7","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes (T2D) is often accompanied by complications and comorbidities. This retrospective study used a large medical claims database to examine the annualized, direct costs associated with T2D-related comorbidities and complications among US adults diagnosed with T2D. It also examined excess costs associated with substandard glycemic control (glycated hemoglobin [HbA1c] ≥ 7%).</p><p><strong>Methods: </strong>Optum's de-identified Market Clarity Data (Optum^® Market Clarity) database was used to identify the 2021-2023 health records of a cohort of adults with T2D. Generalized linear models were used to estimate the age- and sex-adjusted additional costs associated with T2D-related comorbidities and complications. Multivariable analyses were used to examine the costs associated with having HbA1c either within (HbA1c < 7%) or above (HbA1c ≥ 7%) the target range.</p><p><strong>Results: </strong>The study cohort consisted of 108,498 adults, with 50.6% female and average age 66.3 years (standard deviation [SD] = 11.9 years). Results illustrate a substantial burden associated with T2D-related comorbidities. Over half (52.1%) of this cohort of US adults with T2D had three or more comorbidities or complications during the study period, while 22.1% had five or more. The annual, per-person medical costs for these conditions averaged $13,614 and ranged from $5418 (SD = $3598) for knee pain to $23,313 (SD = $11,728) for heart failure. The estimated costs per 100,000 adults with T2D extended from $7.4 million (M) (SD = $8.3M) for severe vision loss/no light perception to $377.4M (SD = $197.9M) for neuropathy. HbA1c above target, compared with HbA1c < 7%, was associated with an additional average annual cost of $5367 per person.</p><p><strong>Conclusion: </strong>The results of this research illustrate potential economic benefits of improving patient comorbidity and complication profiles and achieving HbA1c < 7%. These findings underscore the importance of effective diabetes management strategies that both reduce the risk of complications and alleviate the economic burden on patients and the healthcare system.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Efficacy and Pharmacokinetics of DMB-3115 and its Originator Ustekinumab in Patients with Chronic Plaque Psoriasis: An Exposure-Response Analysis.","authors":"Hironori Konishi, Takeyuki Shindo, Kazuya Ishiwata, Jun Morita","doi":"10.1007/s12325-026-03756-4","DOIUrl":"https://doi.org/10.1007/s12325-026-03756-4","url":null,"abstract":"<p><strong>Introduction: </strong>DMB-3115 is a biosimilar to ustekinumab (Stelara^®). Although a single-dose study conducted in Europe showed that the pharmacokinetics of DMB-3115 was equivalent to that of ustekinumab, another single-dose study in Japan suggested that the maximum serum concentration (C_max) of DMB-3115 might be slightly lower than that of ustekinumab in the Japanese population. Thus, we conducted a post hoc analysis of randomized controlled studies.</p><p><strong>Methods: </strong>The single-dose DMB-3115-1 and DMB-3115-3 studies enrolled healthy participants. The DMB-3115-2 study enrolled patients with moderate-to-severe chronic plaque psoriasis. It comprised 2 periods (Weeks 0-28 and 28-52), and we used the data through Week 12, during which patients received the assigned treatments at Weeks 0 and 4. Across all studies, participants were randomized to receive subcutaneous DMB-3115 or Stelara. We conducted regression analysis to investigate the relationships between the C_max and efficacy outcomes using the data of participants receiving DMB-3115 or Stelara in the DMB-3115-2 study. We also conducted population pharmacokinetic (PK) analysis using the data of participants receiving DMB-3115 in the DMB-3115-1, -2, and -3 studies. Based on its results, we simulated the C_max in the Japanese population.</p><p><strong>Results: </strong>In the regression analysis, the combined C_max of DMB-3115 and ustekinumab was not statistically associated with the percent change in Psoriasis Area and Severity Index (PASI) score from baseline to Week 12 or PASI-75 achievement (at least 75% improvement from baseline) at Week 12. Additionally, the gradual slopes of the regression line and curve suggested that the difference in C_max is not expected to have a meaningful impact on clinical efficacy. In the population PK analysis, the simulated maximum concentrations in the Japanese population were within the range of those observed in the DMB-3115-2 study.</p><p><strong>Conclusion: </strong>The difference in C_max of DMB-3115 is not expected to have a meaningful impact on its efficacy.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics, Safety, and Immunogenicity of DMB-3115, a Ustekinumab Biosimilar for Immune-Mediated Diseases, in Healthy Japanese Male Participants: A Randomized, Double-Blind, Single-Dose Study.","authors":"Hironori Konishi, Takeyuki Shindo, Michio Yagi, Takashi Eto, Rie Yazawa, Makoto Yono, Naoki Cho, Hideki Fushimi, Jun Morita","doi":"10.1007/s12325-026-03755-5","DOIUrl":"https://doi.org/10.1007/s12325-026-03755-5","url":null,"abstract":"<p><strong>Introduction: </strong>DMB-3115 is a biosimilar to ustekinumab (Stelara®). We conducted a randomized controlled study to determine the similarity of bioavailability between DMB-3115 and Stelara (distributed in Japan) in healthy Japanese participants.</p><p><strong>Methods: </strong>Healthy Japanese male participants aged 18 to 55 years were randomly assigned in a 1:1 ratio to receive a single subcutaneous injection (45 mg) of DMB-3115 or Stelara. Participants were followed for 112 days. The primary pharmacokinetic (PK) endpoints were area under the concentration-time curve from time zero to the final sampling time point t (AUC_t) and maximum serum concentration (C_max).</p><p><strong>Results: </strong>This study was conducted between April 11, 2022 and November 22, 2022. A total of 150 participants (75 in each group) received the study drug and were included in the safety analysis, whereas 147 participants (74 in the DMB-3115 group and 73 in the Stelara group) with properly measured PK data were included in the PK analysis. The 90% confidence interval (CI) for the geometric least squares mean (LSM) ratio (DMB-3115/Stelara) of AUC_t (n = 74/73) ranged from 0.826 to 1.011, which was contained within the prespecified bioequivalence range of 0.80 to 1.25. By contrast, the 90% CI for the geometric LSM ratio of C_max (n = 74/73) ranged from 0.762 to 0.984. The proportion of participants experiencing any adverse event (AE) was 37.3% (28 participants) in the DMB-3115 group and 48.0% (36 participants) in the Stelara group. The most common AE in the DMB-3115 group (n = 75) was blood creatine phosphokinase increased. All AEs were mild or moderate in severity. The proportions of participants with post-dose anti-drug antibodies and neutralizing antibodies were lower in the DMB-3115 group (n = 75).</p><p><strong>Conclusion: </strong>Bioavailability of DMB-3115 was considered similar to that of Stelara in the Japanese population. DMB-3115 was well tolerated without any new safety concern.</p><p><strong>Trial registration: </strong>Clinical Trial Registration Japan Registry of Clinical Trials (jRCT2071210135; registered March 22, 2022).</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Examination into the Anti-stress and Anti-fatigue Effects of an Ashwagandha Extract (Ashwa.30™) in Stressed Adults: A Randomised, Double-Blind, Placebo-controlled Trial.","authors":"Adrian L Lopresti, Stephen J Smith, Bharathi Bethapudi, Auxi Arobana R, Deepak Mundkinajeddu, Prashanth D'Souza, Suresh Lakshmikanthan","doi":"10.1007/s12325-026-03740-y","DOIUrl":"https://doi.org/10.1007/s12325-026-03740-y","url":null,"abstract":"<p><strong>Introduction: </strong>Ashwagandha supplementation has been associated with reduced self-reported stress and anxiety, although most trials have used doses of 250-600 mg daily for 6-8 weeks. This study examined the effects of a low-dose ashwagandha extract (Ashwa.30™) on perceived stress, mood, fatigue, and stress reactivity in stressed adults.</p><p><strong>Methods: </strong>In this 28-day, randomised, double-blind, placebo-controlled trial, 60 adults aged 18-65 years with self-reported stress were randomly allocated to receive ashwagandha 30 mg/day or placebo. Outcomes included the Depression, Anxiety, and Stress Scale, daily mood ratings, and the Chalder Fatigue Scale. The Socially Evaluated Cold-Pressor Test (SECPT) was conducted on Days 7 and 28, with subjective stress and fatigue, cardiovascular and electrodermal measures, skin temperature, and salivary cortisol and chromogranin A assessed.</p><p><strong>Results: </strong>Compared to the placebo, ashwagandha intake was associated with greater reductions in self-reported stress in the full analysis set (primary analysis; p = 0.046). The per protocol set analysis was directionally consistent but not statistically significant. Mean daily stress ratings were also lower in the ashwagandha group (p = 0.043). During the Day 28 SECPT, the ashwagandha group reported lower stress ratings (p = 0.044), and salivary cortisol concentrations remained relatively stable in the ashwagandha group but increased in the placebo group, suggesting attenuation of cortisol reactivity (p = 0.047). However, no statistically significant between-group differences were detected for other secondary and physiological outcomes.</p><p><strong>Conclusions: </strong>An ashwagandha extract (Ashwa.30™) administered at 30 mg daily was associated with reduced self-reported stress in the Full Analysis Set and attenuation of SECPT-related salivary cortisol reactivity. These preliminary findings support further investigation in larger, adequately powered trials.</p><p><strong>Trial registration: </strong>Australian and New Zealand Clinical Trials Registry: (ACTRN12625000129482) https://www.anzctr.org.au/ACTRN12625000129482p.aspx .</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}