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Objective: Our aim was to assess efficacy and safety of Rituximab (RTX) in patients with refractory Idiopathic inflammatory myopathies (IIM) from a monocentric cohort. Thereafter, we evaluated the efficacy of a low-dose RTX regimen as a remission-maintenance therapy., Methods: We retrospectively evaluated a cohort of patients affected with IIM treated with RTX. All patients were refractory to glucocorticoids (GC) and at least one immunosuppressant. Two infusions of 1 g two weeks apart were considered as standard cycle of RTX, a single dose of 1 g every six months was deemed as a low-dose RTX regimen. Complete and partial response were defined according to physician's judgment, laboratory and radiological features., Results: Thirty-six patients affected with IIM were enrolled. Eighteen patients (50%) required the use of RTX for muscular involvement, 6 (16.7%) for interstitial lung disease (ILD), 12 (33.3%) for both myositis and ILD. We observed complete response to RTX in 25 patients (69.4%), partial response in 7 (19.4%) and no response in 4 (11.1%), with an overall response of 88.8% (partial and complete response). From the subgroup of twenty-five patients that achieved a complete response, six were treated with a low dose maintenance therapy maintaining a complete response to RTX. Twenty-six patients who achieved a complete or partial response were able to decrease the mean daily GC dose. Infections were the major adverse events detected in our study., Conclusions: RTX shows favorable outcomes in refractory patients with IIM. A low-dose regimen of RTX appears to be effective in maintaining remission after induction with standard dose. Key Points • The precise pathogenic mechanism of idiopathic inflammatory myopathies (IIM) remains elusive; however, a growing body of data support the autoimmune hypothesis. In this context, rituximab, a B cell-depleting agent, has emerged as a second-line therapeutic option in IIM. • Several studies have assessed It its effectiveness in refractory IIM patients. • Limited information exists on the use of Rituximab as maintenance therapy in patients who have achieved remission following induction therapy with Rituximab., (© 2024. The Author(s).)

Objective: Bipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ)., Methods: We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7)., Results: Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses., Conclusions: This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.

Ethnopharmacological Relevance: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by non-specific inflammation. Managing UC presents significant challenges due to its chronic nature and high recurrence rates. Indigo naturalis has emerged as a potential therapeutic agent in clinical UC treatment, demonstrating advantages in alleviating refractory UC and maintaining remission periods compared to other therapeutic approaches., Aim of Review: This review aims to elucidate the potential mechanisms underlying the therapeutic effects of indigo naturalis in UC treatment, assess its clinical efficacy, advantages, and limitations, and provide insights into methods and strategies for utilizing indigo naturalis in UC management., Materials and Methods: Comprehensive data on indigo naturalis were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration., Results: Clinical studies have demonstrated that indigo naturalis, either alone or in combination with other drugs, yields favorable outcomes in UC treatment. Its mechanisms of action involve modulation of the AHR receptor, anti-inflammatory properties, regulation of intestinal flora, restoration of the intestinal barrier, and modulation of immunity. Despite its efficacy in managing refractory UC and prolonging remission periods, indigo naturalis treatment is associated with adverse reactions, quality variations, and inadequate pharmacokinetic investigations., Conclusion: The therapeutic effects of indigo naturalis in UC treatment are closely linked to its ability to regulate the AHR receptor, exert anti-inflammatory effects, mcodulate intestinal flora, restore the intestinal barrier, and regulate immunity. Addressing the current shortcomings, including adverse reactions, quality control issues, and insufficient pharmacokinetic data, is crucial for optimizing the clinical utility of indigo naturalis in UC management. By refining patient-centered treatment strategies, indigo naturalis holds promise for broader application in UC treatment, thereby alleviating the suffering of UC patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Maintenance therapy following first-line chemotherapy is of particular significance in patients diagnosed with recurrent or metastatic nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to investigate the impact of maintenance therapy (MT) on the survival prognosis of individuals with recurrent or metastatic NPC., Methods: The databases Embase, PubMed, and the Cochrane Library were thoroughly searched in a comprehensive manner. Prospective studies of MT for recurrent or metastatic NPC are required. Study endpoints included progression-free survival (PFS) and overall survival (OS)., Results: Two randomized controlled clinical trials, with a total of 294 participants, were analyzed. The maintenance therapy group consisted of 140 participants, while the remaining participants were in the non-maintenance therapy (non-MT) group. The MT group showed a notable enhancement in PFS compared to the non-MT group, with a hazard ratio(HR) of 0.44 and a 95% Confidence interval [CI] of 0.34-0.58 (p < 0.0001). Overall survival was also significantly improved (HR0.42, 95% CI 0.30-0.58; p < 0.0001). The incidence of grade 3 or 4 side effects in the MT group was leukopenia (2.9%), thrombocytopenia (0.7%), and anemia (4.3%), hand-foot syndrome (5.8%), and thrombocytopenia (0.7%). oral mucositis (1.5%), and nausea and vomiting (2.2%)., Conclusions: Maintenance therapy with S-1 (tegafur/gimeracil/oltiracetam) or capecitabine following first-line chemotherapy significantly enhanced OS and PFS in patients with recurrent or metastatic nasopharyngeal carcinoma, while exhibiting minimal incidence of grade 3-4 side effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Pre-HSCT disease control, suboptimal long-term prognosis, and a high recurrence incidence (RI) continue to pose significant challenges for hematopoietic stem cell transplantation (HSCT) in juvenile myelomonocytic leukemia (JMML) patients., Methods: This retrospective cohort study assessed the effectiveness of a decitabine (DAC)-based protocol in JMML patients undergoing HSCT. The pre-HSCT treatment includes initial and bridging treatment. The efficacy of DAC monotherapy versus DAC combined with cytotoxic chemotherapy(C-DAC) as initial treatment was compared, followed by DAC plus FLAG (fludarabine, cytarabine, and GCSF) as bridging treatment. The HSCT regimens were based on DAC, fludarabine, and busulfan. Post-HSCT, low-dose DAC was used as maintenance therapy. The study endpoints focused on pretransplantation simplified clinical response and post-HSCT survival., Results: There were 109 patients, including 45 receiving DAC monotherapy and 64 undergoing C-DAC treatment. 106 patients completed bridging treatment. All patients were administered planned HSCT regimens and post-HSCT treatment. The initial treatment resulted in 88.1% of patients achieving clinical remission without a significant difference between the DAC and C-DAC groups ( p= 0.769). Clinical remission rates significantly improved following bridging treatment ( p= 0.019). The 5-year overall survival, leukemia-free survival, and RI were 92.2%, 88.4%, and 8.0%, respectively. A poor clinical response to pre-HSCT treatment emerged as a risk factor for OS (hazard ratio: 9.8, 95% CI: 2.3-41.1, p= 0.002)., Conclusion: Implementing a DAC-based administration strategy throughout the pre-HSCT period, during HSCT regimens, and in post-HSCT maintenance significantly reduced relapse and improved survival in JMML patients. Both DAC monotherapy and the DAC plus FLAG protocol proved effective as pre-HSCT treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Peng, Gao, Huang, He, Tang, Zong, Pei, Pei, Ge, Liu, Yue, Zhou, Li, Yue, Chen, Chen, Wu, Feng and Li.)

Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication., Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software., Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01)., Conclusion: The study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yuefeng Zhang reports financial support was provided by Medical and health science and technology plan of Zhejiang province of China. Yuefeng Zhang reports a relationship with Medical and health science and technology plan of Zhejiang province of China that includes: employment. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Introduction: Studies have found associations between Opioid Agonist Maintenance Treatment during incarceration and reduced recidivism among recently released formerly incarcerated persons. However, the role of community-based Opioid Agonist Maintenance Treatment in reducing recidivism post-release remains less explored. This study examines whether pre-release arranged, prison-to-rehabilitation Opioid Agonist Maintenance Treatment in the community following release is associated with reduced rates and lengths of re-incarceration among justice-involved individuals with Opioid Use Disorder., Methods: A retrospective matched cohort study was conducted using linked records of 208 individuals with a history of Opioid Use Disorder and treatment during their incarceration. The primary predictor variable was the duration of Opioid Agonist Maintenance Treatment, with re-incarceration rates and lengths of stay after re-incarceration being the primary outcomes examined., Results: Analysis showed a significant decrease in re-incarcerations and or lengths of stay in prison among those who have been re-incarcerated and have undergone Opioid Agonist Maintenance Treatment in the community for >24 months., Conclusions: Maintaining Opioid Agonist Maintenance Treatment over 24 months may reduce re-incarcerations, and may be significantly associated with a reduction in the length of prison stay for re-incarcerated individuals. The effects were consistent across the overall population and the individuals receiving the treatment. Various other unmeasured factors, including judicial discretion, individual motivation, type of offense, and employment status, could influence this association., Competing Interests: Declaration of competing interest Author PS, author PR, author TD, author HBN, author SM, author RB and author BS declare that they have no conflict of interest. The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately. Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498). Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies. Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Shao, Zhao, Xue and Zheng.)

Some patients with neuromyelitis optica spectrum disorder (NMOSD) experience relapse after rituximab (RTX) treatment. In this retrospective study, we analyzed the recurrence-related clinical features, laboratory investigation results, and dosing protocol of 30 female patients with relapsing NMOSD with immunoglobulin G autoantibodies against aquaporin-4 and relapses during repeated 0.5 g RTX infusions as maintenance treatment. The median follow-up period was 6.62 years. Thirty-five episodes were observed, with myelitis being the most frequent. The median expanded disability status scale change score was 0.50. The recurrence rate decreased by 44.23%/year with RTX infusion. Approximately 85.71% of the patients showed relapse without RTX infusion within 10 months. Overall, RTX may be effective for relapsing NMOSD cases., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP)., Methods: This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice., Results: Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died., Conclusion: Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies., Competing Interests: SHP has served in consulting or advisory roles for Janssen; reports honoraria from Merck, Ono Pharmaceutical, and Pfizer; and reports research funding from Ono Pharmaceutical and Sanofi. SYR reports advisory roles and speaker services for and has received research funding from Merck. HKS has received research funding from Astellas, AstraZeneca, Basilea, Janssen, Merck, MSD, Ono-BMS, and Roche; and reports consulting, advisory roles, and speaker services for Astellas, Boehringer Ingelheim, Janssen, MSD, Ono-BMS, and Roche. BK has served in advisory roles for ABL Bio, AstraZeneca, CbsBioscience, Cellid, Genexine, Handok, Merck, MSD, and Trial Informatics; reports speaker services from AstraZeneca, Merck, and MSD; and served as coordinating principal investigator for AstraZeneca, MSD, and Ono Pharmaceutical. MK has served in consulting or advisory roles for Eisai, Ipsen, MSD, Ono-BMS, and Yuhan. Y-HH reports employment at Merck Ltd., Seoul, Republic of Korea, an affiliate of Merck KGaA. J-LL reports stock and other ownership interests in Amgen, Black Diamond Therapeutics, Innovent Biologics, Johnson & Johnson/Janssen, Karyopharm Therapeutics, Merck, and Zymeworks; reports honoraria from Astellas, AstraZeneca, BMS, MSD, and Pfizer; has served in consulting or advisory roles for AstraZeneca, BMS, GI Innovation, Merck, MSD, Oscotec, Pfizer, and Sanofi; and has received institutional research funding from Amgen, AstraZeneca/MedImmune, Bayer Schering Pharma, BMS, GI Innovation, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Seagen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Merck Ltd. The funder had the following involvement in the study: providing administrative roles for the present study., (Copyright © 2024 Park, Shin, Rha, Beom, Seo, Keam, Kim, Hong, Yoon and Lee.)

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD., (© 2024 World Psychiatric Association.)

Purpose: Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC)., Methods: JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay)., Results: No significant interaction between treatment and PD-L1 status was observed for OS. Clinically meaningful and robust survival data were observed in favor of avelumab using the different ≥ 1% TC/IC PD-L1 expression cutoff., Conclusions: These results demonstrate the benefit of avelumab maintenance in la/mUC regardless of PD-L1 expression, consistent with approved labels., (© 2023. The Author(s).)

Objectives: B cell depletion therapy with rituximab is effective in most patients with IgG4-related disease (IgG4-RD) but requires repeated cycles to prevent disease flares. We here aimed to assess B cells after rituximab to predict relapse of IgG4-RD and guide retreatment., Methods: Patients with active IgG4-RD included in this retrospective study fulfilled the ACR/EULAR Classification Criteria. Total CD19+ B cells, plasmablasts, naïve and memory B cells were measured on peripheral blood by flow-cytometry at baseline and six months after rituximab. All patients were treated with two 1 g infusions of rituximab 15 days apart and monitored for 48 months. Disease response was assessed using the IgG4-RD Responder Index., Results: Thirty-three patients were included. Six months after rituximab, disease response was observed in all patients. Complete depletion of CD19+ B cells, plasmablasts, naïve and memory B cell depletion was achieved in 30%, 55%, 39%, and 42% of cases, respectively. Twenty-three relapses (70%) were observed at a median time of 24 months after rituximab. Relapse rate was significantly higher in patients who failed to achieve complete depletion of CD19+ cells (60% vs 17%, p= 0.02), naïve B cells (54% vs 15%, p= 0.01), or memory B cells (50% vs 16%, p= 0.03) six months after rituximab. The median relapse free survival time was shorter in patients who failed to achieve complete depletion of CD19+ cells (19 vs 38 months, p= 0.02), naïve B cells (16 vs 38 months, p= 0.01), or memory B cells (19 vs 38 months, p= 0.03) six months after rituximab., Conclusions: The degree of B cell depletion six months after rituximab may predict disease flare and may instruct on the pacing of B cell depletion therapy in IgG4-RD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Long-acting injectable (LAI) antipsychotics are recommended in the treatment non-adherence. Despite the widespread use of LAI antipsychotics, there is limited data on clinical outcomes in bipolar I disorder (BD-I) patients with real-world data. We aimed to compare BD-I patients treated with LAI and oral antipsychotics (OAP) in terms of treatment effectiveness in a 1-year follow-up period., Methods: The study was conducted retrospectively with electronic health records of 116 BDI patients. The primary outcomes were whether patients in the LAI group and the OAP group differed in relapse, rehospitalization, emergency room (ER) visits, and all-cause treatment discontinuation at 1-year follow-up after a mania episode. Cox regression modeling was used to predict the recurrence of any mood episode and all-cause treatment discontinuation during follow-up. The secondary outcomes evaluated were the effects of sociodemographic and clinical parameters and concomitant psychotropic medications on the course of the illness and treatment adherence., Results: Of all 116 patients, 33 (28.4%) were under LAI, and 83 (71.6%) were under OAP treatment. LAI users had a history of more hospitalizations and total mood episodes. Patients in the LAI group had more treatment non-adherence before the index hospitalization. At 1-year follow-up, there was no difference between the groups in terms of any mood relapse, rehospitalization, ER visits, and all-cause treatment discontinuation. As a secondary outcome, lithium users were found to have fewer new episodes and discontinuations of treatments., Conclusions: In real-world data, there is no evidence that LAI antipsychotics (compared to OAP) are superior in the maintenance treatment of BD. These results are important in terms of reflecting clinical practices for the treatment of BD-I. These results do not devalue the use of LAI therapy in BD; however, more studies are needed to identify positive predictors for LAI treatments in BD.

Background: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment., Methods: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit., Results: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM., Limitations: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times., Conclusion: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In the phase 3 QUAZAR AML-001 trial (NCT01757535) of patients with acute myeloid leukaemia (AML) in remission following intensive chemotherapy (IC) and ineligible for haematopoietic stem cell transplant (HSCT), oral azacitidine (Oral-AZA) maintenance significantly prolonged overall survival (OS) versus placebo. The impact of subsequent treatment following maintenance has not been evaluated. In this post hoc analysis, OS was estimated for patients who received subsequent AML therapy, and by regimen received (IC or lower-intensity therapy). First subsequent therapy (FST) was administered after treatment discontinuation in 134/238 Oral-AZA and 173/234 placebo patients. OS from randomization in patients who received FST after Oral-AZA versus placebo was 17.8 versus 12.9 months (HR: 0.82 [95% CI: 0.64-1.04], median follow-up: 56.7 months); OS from FST was similar between arms. Among patients who received injectable hypomethylating agents as FST, median OS was 8.2 versus 4.9 months in the Oral-AZA versus placebo groups (HR: 0.66 [95% CI: 0.41-1.06]). Forty-eight patients (16/238 Oral-AZA, 32/234 placebo) received HSCT following treatment discontinuation, including six Oral-AZA patients still in first remission; Oral-AZA OS benefit persisted when censoring these patients. Oral-AZA maintenance can prolong AML remission duration without negatively impacting survival outcomes after salvage therapies., (© 2023 Bristol Myers Squibb and The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Melasma is a chronic hypermelanosis of the skin that affects approximately 1% of the global population, predominantly affects women, and is more prevalent in skin of color. Melasma is a common driver for patients with skin of color to seek out a dermatologist for treatment, and ensuring the right approach for these patients is important because some treatments may be associated with adverse side effects. Because of the chronicity of the disease and established psychosocial and emotional impacts, there is a large need to ensure care follows the best available evidence on the treatment of patients with melasma., Objective: Here, we summarized current available topical treatments for melasma with considerations dermatologists should have for their patients with skin of color., Methods: Steering committee consensus on clinical best practices., Results: We describe a flexible and focused treatment algorithm that reflects both treatment and maintenance periods that is a consensus of our extensive clinical experience., Limitations: Use of real-world evidence and potential for individual practice bias., Conclusion: Melasma can be challenging to treat, particularly in patients with skin of color, and our recommendations for best practices for patients in the United States are an important step toward standardizing care., Competing Interests: Conflicts of interest Dr Desai has served as a consultant and/or investigator for Galderma, Pfizer, Dermavant, Scientis, AbbVie, and several other organizations. He also serves in multiple leadership roles with dermatologic organizations. Dr Alexis has received grants from LEO Pharma, Novartis, Almirall, Bristol Myers Squibb, Amgen, Vyne, Galderma, Valeant (now Bausch Health), Cara, Arcutis, Dermavant, AbbVie, and Castle and consulting fees or honoraria from Leo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Beiersdorf, Ortho, L’Oreal, Bristol Myers Squibb, Bausch Health, UCB, Vyne, Arcutis, Janssen, Allergan, Almirall, AbbVie, Sol-Gel, Amgen, VisualDx, Eli Lilly, Swiss American, Cutera, Cara, EPI, and Incyte. He has also received speaker fees from Regeneron, Sanofi-Genzyme, Pfizer, and Bristol Myers Squibb. Dr Elbuluk has received fees, research funding, or stock options for consulting, speaking, or participating in advisory boards from Allergan, Avita Medical, Beiersdorf, Estée Lauder, Galderma Laboratories, Incyte, Janssen, La Roche-Posay, L’Oreal, Scientis, Unilever, and VisualDx. Dr Grimes has served as a consultant and/or investigator for Procter & Gamble, Clinuvel, L’Oreal, Galderma Laboratories, LaserOptek, Versicolor Technologies, Incyte, Pfizer, AbbVie/Allergan, and SkinBetterScience. Dr Weiss served on the advisory board for Galderma Laboratories and Valeant Pharmaceuticals International (now Bausch Health), receiving honoraria. He also served as consultant for Abbott Laboratories, Celgene Corporation, LEO Pharma, and Sebacia, receiving honoraria. Dr Hamzavi is a consultant to AbbVie, Pfizer, Incyte, UCB, Boerhinger Ingelheim, Sonoma, Union therapeutics, Novartis, Janssen, Avita, and for Galderma Laboratories. Dr Hamzavi is an investigator for LENICURA, Pfizer, Incyte, Avita, and L’Oreal/La Roche-Posay. He is a board member and past president of the HS Foundation and Global Vitiligo Foundation. Dr Taylor reports service as an investigator for Concert Pharmaceuticals, Croma-Pharma, Eli Lilly, and Pfizer. Dr Taylor has received salaries, fees, honoraria, and stock options as a consultant, advisor, board member, and speaker for Mercer Strategies, AbbVie, Arcutis Biotherapeutics, Armis Scientific, Beiersdorf, Biorez, Cara Therapeutics, EPI Pharma, Evolus, Galderma Laboratories, Glo Getter, Hugel America, Janssen, Johnson & JohnsonJohnson & Johnson, L’Oreal, Medscape/WebMD, MJH Life Sciences, Piction Health, Regeneron, Scientis US, UCB, and Vichy Laboratoires., (Published by Elsevier Inc.)

Background: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients., Methods: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment., Results: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy., Conclusions: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression-free survival (PFS) of 6-16 months. Ibrutinib penetrates the blood-brain barrier and has shown activity in PCNSL., Methods: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2-year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60-85 years old who responded to first-line high-dose methotrexate (HDMTX)-based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity., Results: Twenty patients were enrolled, with a median age of 72 years (range, 61-80). Median time on ibrutinib maintenance was 12.5 (range, 2-46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1- and 2-year PFS are 90% and 72.6%, respectively, and the 2-year OS is 89%., Conclusions: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly., (© 2023 American Cancer Society.)

Introduction: Durvalumab is a check-point inhibitor against programmed death ligand-1 (PD-L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES-SCLC patients., Methods: This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum-based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., Discussion: We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES-SCLC patients., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

The JAVELIN Bladder 100 phase III trial led to the incorporation of avelumab first-line (1L) maintenance treatment into international guidelines as a standard of care for patients with advanced urothelial carcinoma (UC) without progression after 1L platinum-based chemotherapy. JAVELIN Bladder 100 showed that avelumab 1L maintenance significantly prolonged overall survival (OS) and progression-free survival in this population compared with a 'watch-and-wait' approach. The aim of this manuscript is to review clinical studies of avelumab 1L maintenance in patients with advanced UC, including long-term efficacy and safety data from JAVELIN Bladder 100, subgroup analyses in clinically relevant subpopulations, and 'real-world' data obtained outside of clinical trials, providing a comprehensive resource to support patient management. Extended follow-up from JAVELIN Bladder 100 has shown that avelumab provides a long-term efficacy benefit, with a median OS of 23.8 months measured from start of maintenance treatment, and 29.7 months measured from start of 1L chemotherapy. Longer OS was observed across subgroups, including patients who received 1L cisplatin + gemcitabine, patients who received four or six cycles of 1L chemotherapy, and patients with complete response, partial response, or stable disease as best response to 1L induction chemotherapy. No new safety signals were seen in patients who received ≥1 year of avelumab treatment, and toxicity was similar in those who had received cisplatin or carboplatin with gemcitabine. Other clinical datasets, including noninterventional studies conducted in Europe, USA, and Asia, have confirmed the efficacy of avelumab 1L maintenance. Potential subsequent treatment options after avelumab maintenance include antibody-drug conjugates (enfortumab vedotin or sacituzumab govitecan), erdafitinib in biomarker-selected patients, platinum rechallenge in suitable patients, nonplatinum chemotherapy, and clinical trial participation; however, evidence to determine optimal treatment sequences is needed. Ongoing trials of avelumab-based combination regimens as maintenance treatment have the potential to evolve the treatment landscape for patients with advanced UC., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

For over half a century, it has been widely known that lithium is the most efficacious maintenance treatment for bipolar disorder. Despite thorough research on the long-term effects of lithium on renal function, a number of important questions relevant to clinical practice remain. The risk of polyuria, reflecting renal tubular dysfunction, is seen in a substantial proportion of patients treated with long term lithium therapy. The duration of lithium may be the most important risk factor for lithium-induced polyuria. Most, but not all, studies find that lithium is associated with higher rates of chronic kidney disease compared to either age matched controls or patients treated with other mood stabilizers. Age, duration of lithium therapy and medical disorders such as hypertension and diabetes mellitus are risk factors for chronic kidney disease in lithium-treated patients. The relationship between polyuria and chronic kidney disease is inconsistent but poorly studied. Although not all studies agree, it is likely that lithium may increase the risk for end stage renal disease but in a very small proportion of treated patients. Patients whose renal function is relatively preserved will show either no progression or improvement of renal function after lithium discontinuation. In contrast, patients with more renal damage frequently show continued deterioration of renal function even after lithium discontinuation. Optimal management of lithium treatment requires obtaining a baseline measure of renal function (typically estimated glomerular filtration rate [eGFR]) and regular monitoring of eGFR during treatment. Should the eGFR fall rapidly or below 60 ml/minute, patients should consider a consultation with a nephrologist. A decision as to whether lithium should be discontinued due to progressive renal insufficiency should be made using a risk/benefit analysis that takes into account other potential etiologies of renal dysfunction, current renal function, and the efficacy of lithium in that individual patient., (© 2023. The Author(s).)

Purpose: This study assessed and compared preferences for treatment attributes of maintenance therapies post-hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and in physicians who treat these patients., Patients and Methods: Patients with AML post HSCT and physicians from the United States, United Kingdom, Canada, and Australia (physicians only) completed a web-based discrete choice experiment (DCE). The DCE used inputs identified via a targeted literature review and qualitative interviews to ascertain relevant treatment attributes and associated levels. Six treatment attributes were selected (chance of 2-year relapse-free survival, quality of life [QoL], risk of serious infections, risk of nausea, chance of achieving transfusion independence, and duration of hospitalization annually), each with three or four levels. The experimental design included 36 choice tasks that presented a pair of hypothetical treatment profiles with varying attribute levels; participants chose a preferred treatment for each choice task. Choice tasks were divided into three blocks of 12 tasks each in the patient survey and 4 blocks of 9 tasks each in the physician survey; survey participants were randomly assigned to one of the blocks. Random parameter logit regression models were used to assess the impact of stated attributes on preferences for maintenance treatment post HSCT., Results: Surveys from 84 patients and 149 physicians were assessed. For patients, QoL was the most important attribute, followed by duration of hospitalization and chance of 2-year relapse-free survival. For physicians, chance of 2-year relapse-free survival was the most important attribute, followed by QoL and risk of serious infections., Conclusion: Differences in how patients and physicians valued post-HSCT maintenance treatment attributes were identified. These differences suggest that patient-centered decision-making may help physicians choose maintenance treatments for patients with AML post HSCT that better meet their treatment needs and improve their treatment satisfaction., Competing Interests: Lalit Saini received consulting fees and honoraria for participation on an advisory board from Astellas. James D. Griffin received consulting fees from Astellas and reports grants from Novartis Pharma, outside the submitted work. Bhavik J. Pandya is an employee of Astellas. Manasee V. Shah is a former employee of Astellas. Mo Zhou received consulting fees paid to Analysis Group from Astellas. Hongbo Yang received consulting fees paid to Analysis Group from Astellas. Yan Song received consulting fees paid to Analysis Group from Astellas. Deborah A. Marshall received consulting fees from Astellas. She also reports travel expenses and honorarium from ISPOR, travel expenses from Illumina, and consulting services paid to institution (UCalgary) from Novartis, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Saini et al.)

Standard-of-care first-line treatment for metastatic urothelial carcinoma (mUC) is platinum-based chemotherapy (CTx). Maintenance immunotherapy is a treatment option for patients without progressive disease (PD) after induction CTx. IMvigor130 was a randomised, phase 3 study evaluating atezolizumab plus platinum-based CTx (arm A), atezolizumab monotherapy (arm B), or placebo plus platinum-based CTx (arm C) as first-line treatment for mUC. The primary progression-free survival (PFS) analysis showed a statistically significant PFS benefit favouring arm A versus arm C, which did not translate into overall survival (OS) benefit at the final OS analysis. We report exploratory analyses based on response to combination induction treatment (arm A vs arm C) using final OS data. Post-induction OS was analysed for patients without PD during induction (4-6 CTx cycles) who received at least one dose of single-agent atezolizumab/placebo maintenance treatment. Post-progression OS was analysed for patients with PD during induction CTx. Addition of atezolizumab to CTx did not impact OS outcomes, regardless of response to induction CTx, with hazard ratios of 0.84 (95% confidence interval [CI] 0.63-1.10) for patients without PD and 0.75 (95% CI 0.54-1.05) for those with PD during induction CTx. Treatment effects appeared to be greatest for patients treated with cisplatin and for those with PD-L1-high tumours., Patient Summary: The IMvigor130 trial showed that addition of atezolizumab to chemotherapy (CTx) did not improve survival over CTx alone in patients with bladder cancer. Overall, patients whose cancer did not progress during initial treatment tended to live longer than patients whose cancer did progress, but addition of atezolizumab to CTx did not help either group live longer in comparison to CTx alone. However, the results suggest that patients who received a certain CTx drug (cisplatin) or who had high levels of a marker called PD-L1 in their tumour may get the most improvement from addition of atezolizumab to CTx.The IMvigor130 trial is registered on ClinicalTrials.gov as NCT02807636., (© 2023 The Authors.)

Introduction: No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine., Methods: This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use., Results: Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28-4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68-16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73-2.70; p = 0.30)., Conclusion: The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Individuals with panic disorder frequently face ongoing symptoms, suboptimal treatment adherence, and increased relapse rates. Although mobile health interventions have shown promise in improving treatment outcomes for numerous mental health conditions, their effectiveness, specifically for panic disorder, has yet to be determined., Objective: This study investigates the effects of a mobile-aided case management program on symptom reduction and quality of care among individuals with panic disorder., Methods: This 3-year cohort study enrolled 138 participants diagnosed with panic disorder. One hundred and eight participants joined the mobile-aided case management group and 30 in the treatment-as-usual group. Data were collected at baseline, 3-month, 6-month, and 12-month treatment checkpoints using self-report questionnaires, in-depth interviews, direct observation, and medical record analysis., Results: During the maintenance treatment phase, the mobile-assisted case management group decreased both panic severity ( p  = 0.008) and state anxiety ( p  = 0.016) more than the control group at 6 months. Participants who underwent case management experienced enhanced control over panic symptoms, heightened self-awareness, and elevated interpersonal support., Conclusion: The mobile-aided case management is beneficial in managing panic disorder, especially maintenance treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tsai, Christian and Lai.)

For patients with advanced gastric cancer after chemotherapy, the optimal mode of maintenance therapy is not yet clear. This research aimed to compare the efficacy and adverse effects of S-1 maintenance therapy and follow-up observation in patients with advanced gastric cancer without disease progression after first-line combined chemotherapy. This study retrospectively analyzed 106 patients from January 2018 to December 2021. The primary endpoints were overall survival and progression-free survival, the secondary endpoint was chemotherapy-related toxicity, and the curative effects and baseline characteristics of the patients were analyzed. Longer progression-free survival and overall survival were observed in the S-1 maintenance treatment group than in the follow-up observation group ( p  < 0.001). No obvious differences existed in the subgroup results regarding progression-free survival or overall survival ( p  > 0.05). In the maintenance treatment group, the occurrence of thrombocytopenia and hand-foot syndrome was significantly increased ( p  < 0.001). No toxicity-related deaths occurred. The included patients without disease progression after first-line combined chemotherapy can achieve significant survival benefits by receiving S-1 maintenance therapy. The patient's tolerance to S-1 maintenance therapy was good., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Lupus nephritis (LN) treatment aims to control and prevent flares and irreversible kidney damage. Around 30% of patients are unresponsive to treatment; however, real-world LN treatment patterns have not been reported. Objectives of this retrospective cohort study (GSK 209758) were to quantify the time to switching/re-initiating induction therapy in patients with LN initiating immunosuppressant therapy and conversion from induction to maintenance immunosuppressant therapy, and to assess corticosteroid use., Methods: Patients with LN initiating induction or maintenance immunosuppressant therapy were identified using claims data. Patients were followed up from the index date (immunosuppressant initiation date) until treatment discontinuation, death, disenrollment, administrative censoring, or the end of follow-up period. The cumulative incidence of switching/re-initiating induction therapy and conversion to maintenance therapy was estimated using outpatient pharmacy claims and procedure codes. Corticosteroid use was estimated using pharmacy claims; a mean daily dose of ≥ 7.5 mg/day was considered high., Results: In total, 5000 patients with LN contributed 5516 treatment episodes (induction cohort, N = 372; maintenance cohort, N = 5144). In the induction cohort, the cumulative incidence (95% confidence interval) of switching between induction therapies was 24.6% (20.1-30.0) at 12 months, while 59.6% (52.4-66.1) of patients converted to maintenance therapy at 12 months. In the maintenance cohort, 21.2% (19.9-22.5) re-initiated induction therapy at 12 months. Oral corticosteroid use decreased during the follow-up in both cohorts, but 21.5% of patients remained on a high dose at 12 months in the induction cohort, while 15.8% in the maintenance cohort were taking a high dose at 24 months., Conclusions: Around a quarter of patients with LN initiating immunosuppressant therapy switched within 12 months, while a fifth re-initiated induction therapy within 12 months. Use of high corticosteroid doses were observed during 24 months of follow-up. These data suggest that many patients do not respond to existing standard LN therapies., (© 2023. The Author(s).)

Background: No standard maintenance treatment has been obtained to prolong the response duration of soft tissue sarcoma (STS) after first-line chemotherapy. In this study, we aimed to evaluate the efficacy and safety of anlotinib as a maintenance treatment after chemotherapy in STS., Methods: In this multicentre, open-label, single-arm phase 2 trial, patients with advanced STS who achieved partial response or stable disease after first-line anthracycline-based chemotherapy were enrolled between April 2019 and January 2022. All patients received anlotinib as a maintenance treatment. The primary endpoint was progression-free survival (PFS) of anlotinib maintenance treatment. Other endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov, NCT03890068., Findings: At the data cut-off date (August 8, 2022), 49 patients were enrolled, including 17 with liposarcoma (35%) and 15 with leiomyosarcoma (31%). After a median follow-up of 17.1 months (IQR 9.0-27.2), the median PFS from the beginning of maintenance treatment was 9.1 months (95% CI 5.7-12.5), and the median OS was not reached, and the 1-year OS rate for anlotinib maintenance treatment was 98.0%. The best ORR and DCR were 16% (8/49, 95% CI 7-30) and 94% (46/49, 95% CI 83-99), respectively. Most of the treatment-related adverse events were grade 1-2. Of the grade 3-4 adverse events, the most common were hypertension (10%) and hand-foot syndrome reaction (6%)., Interpretation: Postchemotherapy maintenance treatment with anlotinib exhibits promising efficacy and tolerable toxicity in patients with advanced STS., Funding: Chia Tai Tianqing Pharmaceutical Group Co., Ltd., the National Key Research and Development Program of China, and the National Natural Science Foundation of China., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Anti-EGFR antibodies plus doublet chemotherapy is the standard of care in RAS/BRAF wild-type metastatic colorectal cancer (mCRC). No phase-3 level of evidence is available to guide treatment de-escalation after anti-EGFR-based first-line. Several randomised clinical trials investigated de-intensification strategies with 5-fluorouracil/leucovorin (5-FU/LV) and/or anti-EGFR., Methods: We performed an individual patient data pooled analysis of Valentino, Panama, MACRO-2, COIN-B trials including RAS wild-type mCRC patients who received first-line therapy with FOLFOX plus panitumumab or cetuximab followed by pre-specified maintenance strategy. Only patients who started maintenance according to the assigned arm were included. Patients were categorised by type of maintenance (i.e. 5-FU/LV, anti-EGFR or 5-FU/LV + anti-EGFR). Progression-free survival (PFS) and overall survival (OS) were calculated from the start of maintenance; toxicity was evaluated for the maintenance treatment period., Results: A total of 518 patients were included in the pooled analysis. Overall, 123, 185 and 210 patients received maintenance with 5-FU/LV, anti-EGFR, 5-FU/LV + anti-EGFR, respectively. Median PFS was 5.6, 6.0 and 9.0 (P = 0.009) and OS was 25.7, 24.0 and 28.0 months (P = 0.134) in 5-FU/LV, anti-EGFR and 5-FU/LV + anti-EGFR arms, respectively. Monotherapy maintenance (either 5-FU/LV or anti-EGFR) was inferior to combination in terms of PFS (hazard ratios [HR] 1.26, P = 0.016) and non-significantly trending also in OS (HR 1.20, P = 0.111). An increase of overall any grade and grade ≥ 3 AEs and selected AEs was reported in combination compared to either 5-FU/LV or anti-EGFR arms., Conclusions: This pooled analysis including four randomised phase II supports the use of 5-FU/LV plus anti-EGFR as the preferred maintenance regimen. Data provide rational for a more individualised maintenance treatment approach based on tumour and patients features., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AR: Honoraria for lectures from Elma Academy and Servier. Travel support: Amgen. HW: honoraria as a speaker and/or in an advisory role from Pierre Fabre, Merck KGaA, Incyte, Merck Sharp Dohme, Servier, Bayer, Roche Genentech and SIRTEX. EA: Honoraria for advisory role from Amgen, Bayer, Bristol Myers Squibb, Merck, Roche, Sanofi. FM: Honoraria from Servier, Lilly, Pierre-Fabre and received research grants from Incyte. FP: Honoraria from Amgen, Bayer, Servier, Merck-Serono, Lilly, MSD, BMS, Astrazeneca, Astellas, Organon, Pierre-Fabre and received research grants from Bristol-Myers Squibb, Astrazeneca, Agenus, Incyte. DPM: Honoraria for lectures and advisory boards: Merck, Amgen, Servier, Pierre Fabre, Sanofi, Lilly, BMS, MSD, AstraZeneca, G1, Cureteq, Takeda, Taiho, Onkowissen.de; GSK, Seagen, COR2ED. Travel support: Amgen, Servier. Research funding (inst): Amgen, Servier. All other authors declared no disclosures., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background/aim: To determine if maintenance treatment can be performed effectively and safely in patients with platinum-sensitive relapsed ovarian cancer., Patients and Methods: We carried out a multi-center study to investigate progression-free survival (PFS) and adverse events (AEs) in 229 patients receiving maintenance treatment for platinum-sensitive relapsed ovarian cancer., Results: The median PFS in the 229 patients with maintenance treatment was 14.0 months (95% confidence interval=10.3-17.6 months). The hematological toxicities included ≥grade 3 anemia in 33.2% of cases. Anemia during maintenance treatment was significantly more common than anemia during chemotherapy given before maintenance treatment (p<0.001). Anemia during chemotherapy prior to maintenance treatment significantly increased the risk of anemia during maintenance treatment, compared with other clinical features (p<0.001)., Conclusion: Maintenance treatment can be performed safely and effectively in patients with platinum-sensitive relapsed ovarian cancer. Anemia during chemotherapy given before maintenance treatment significantly increased the risk of developing anemia during maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Fluoropyrimidine (FP) with oxaliplatin-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (mCRC); however, oxaliplatin-induced neuropathy critically affects the quality of life of patients. Maintenance strategies with FP plus bevacizumab have been well-established; nonetheless, the real-world outcomes of maintenance therapy with FP and cetuximab are unclear. We investigated the clinical outcomes of patients who underwent maintenance therapy with cetuximab., Methods: We retrospectively identified and analyzed patients with mCRC who were treated between 2012 and 2021 with first-line oxaliplatin-based induction chemotherapy (IC) plus biologic agents (either cetuximab or bevacizumab), and underwent maintenance therapy (IC regimen without oxaliplatin) after IC., Results: In total, 19 patients who were treated with mFOLFOX6 (FP/leucovorin/oxaliplatin) with cetuximab, and 26 patients who were treated with mFOLFOX6 with bevacizumab were included. In the cetuximab group, all patients were KRAS-, NRAS-, and BRAF-wild type, whereas most patients in the bevacizumab group harbored KRAS or BRAF V600E or NRAS mutants. During the maintenance treatment, seven patients (four [21%] in the cetuximab group and three [11%] in the bevacizumab group) achieved partial response after achieving nadir during induction chemotherapy. The disease control rates of maintenance therapy were 79% and 74% in the cetuximab and bevacizumab groups, respectively. The median progression-free survival of maintenance therapy and overall survival was 5.98 months and 32.4 months in the cetuximab group, and 4.83 months and 25.6 months in the bevacizumab group, respectively., Conclusions: Maintenance therapy with FP plus biologic agents (either bevacizumab or cetuximab) is a feasible strategy for appropriate mCRC patients according to their RAS/BRAF status. Further large-scale randomized studies are needed to validate the efficacy of anti-epidermal growth factor receptor-based maintenance therapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China., Methods: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0., Results: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA., Conclusions: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013-01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28-day cycles of pomalidomide 4 mg daily on days 1-21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow-up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression-free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug-related non-haematological AEs (>5%) comprised 13% infections. Long-term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries., Methods: Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety., Results: A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8-NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43-1.26]); median PFS was 5.6 months (95% CI, 2.0-7.5) vs. 1.9 months (95% CI, 1.9-1.9), respectively (HR, 0.58 [95% CI, 0.38-0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%)., Conclusions: Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance as standard of care for Asian patients with advanced UC that has not progressed with first-line platinum-containing chemotherapy. NCT02603432., Competing Interests: Declaration of Competing Interest J.-L. Lee reports stock and other ownership interests in Amgen, BeiGene, Black Diamond Therapeutics, Innovent Biologics, Johnson & Johnson/Janssen, Karyopharm Therapeutics, Myovant Sciences, the healthcare business of Merck KGaA, Darmstadt, Germany, and Zymeworks; has received honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Merck & Co., Kenilworth, NJ, and Pfizer; served in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, GI Innovation, Merck & Co., Kenilworth, NJ, Oscotec, Pfizer, Sanofi Korea, and the healthcare business of Merck KGaA, Darmstadt, Germany; and has received research funding from Amgen, AstraZeneca/MedImmune, Bayer Schering Pharma, Bristol Myers Squibb, GI Innovation, Janssen, Merck & Co., Kenilworth, NJ, Novartis, Pfizer, Roche/Genentech, and Seagen. C. Desai has served in a consulting or advisory role for Novartis, Pfizer, Roche, and the healthcare business of Merck KGaA, Darmstadt, Germany; and has provided speakers services for Dr. Reddy's, Lupin Pharmaceuticals, Novartis, and Pfizer. S. H. Park has served in a consulting or advisory role for Janssen Oncology; has received honoraria from Ono Pharma Korea, Pfizer, and the healthcare business of Merck KGaA, Darmstadt, Germany; and has received research funding from Ono Pharmaceutical and Sanofi. N. Tsuchiya has received honoraria from Astellas, Bayer, Bristol Myers Squibb, Eisai, Janssen, Merck & Co., Kenilworth, NJ, Pfizer, Takeda, and the healthcare business of Merck, KGaA, Darmstadt, Germany; and has received institutional research funding from Eisai. P.-J. Su has served in a consulting or advisory role for Bristol Myers Squibb, Merck & Co., Kenilworth, NJ, Ono Pharmaceutical, Pfizer, and the healthcare business of Merck KGaA, Darmstadt, Germany; and has provided speakers services for Bristol Myers Squibb, Merck & Co., Kenilworth, NJ, Ono Pharmaceutical, Pfizer, Roche, and the healthcare business of Merck KGaA, Darmstadt, Germany. T. T. W. Chan has nothing to disclose. H. Gurney has served in consulting or advisory roles for AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen-Cilag, Merck & Co., Kenilworth, NJ, Pfizer, Roche, and the healthcare business of Merck KGaA, Darmstadt, Germany; reports speakers services for the healthcare business of Merck KGaA, Darmstadt, Germany; and has received travel and accommodations expenses from AstraZeneca. S. Gao reports employment by Merck Pte. Ltd., Singapore, an affiliate of Merck KGaA, Darmstadt, Germany at the time the research was conducted. J. Wang reports employment by Pfizer. R. Sandner reports employment by and stock and other ownership interests in Pfizer. A. di Pietro reports employment by and stock and other ownership interests in Pfizer. M. Eto has served in a consulting or advisory role for AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Eisai, Johnson & Johnson, Ono Pharmaceutical, Pfizer, Takeda, and the healthcare business of Merck KGaA, Darmstadt, Germany; has provided speakers services for Bristol Myers Squibb, Janssen, Merck & Co., Kenilworth, NJ, Novartis, Ono Pharmaceutical, Pfizer, Takeda, and the healthcare business of Merck KGaA, Darmstadt, Germany; and has received research funding from Astellas Pharma, Bayer, Ono Pharmaceutical, Sanofi, and Takeda., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.

Objective: The purpose of this study was to retrospectively assess the pattern, compliance, efficacy and safety of bevacizumab in Chinese ovarian cancer patients., Methods: We reviewed the clinicopathological data of patients with histologically confirmed epithelial ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma, who were diagnosed and treated at the Department of Gynecologic Oncology of Peking University Cancer Hospital between May 2012 and January 2022., Results: A total of 155 patients were eventually enrolled in this study, with 77 as first-line chemotherapy (FL) and 78 as recurrence therapy (RT) among which 37 patients were platinum sensitive and 41 were platinum resistant. Among the 77 patients in the FL group, 35 received bevacizumab during neoadjuvant chemotherapy (NACT) alone (NT), 23 received bevacizumab during both neoadjuvant and first-line chemotherapy (NT + FL) and 19 received bevacizumab during first-line chemotherapy alone (FLA). Among the 43 patients of NT and NT + FL groups undergoing interval debulking surgery (IDS), 38(88.4%) patients achieved optimally debulking and 24 (55.8%) patients had no residual disease after IDS. The patients in the FL group had a median progression free survival (PFS) of 15(95%CI: 9.951-20.049) months, and the 12-month PFS was 61.7%. In the RT group, the overall response rate (ORR) was 53.8%. According to multivariate analysis, the patients' platinum sensitivity had a significant impact on the PFS in the RT group. 13(8.4%) patients discontinued bevacizumab due to toxicity. Seven patients were in the FL group while 4 patients were in the RT group. The most common adverse event associated with bevacizumab therapy was hypertension., Conclusion: Bevacizumab is effective and well-tolerated in the real world setting of ovarian cancer treatment. Adding bevacizumab to NACT is feasible and tolerable. Receiving the regimen containing bevacizumab in the last preoperative chemotherapy did not result in increased intraoperative bleeding of IDS. Platinum sensitivity is the most important factor affecting the effectiveness of bevacizumab in recurrent patients., (© 2023. The Author(s).)

The introduction of inhibitors of poly-(ADP-ribose) polymerase (PARP) for the treatment of women with epithelial ovarian cancers (EOC) has radically changed the treatment in maintenance setting after responding to first- and second-line chemotherapy. The aim of this paper was to assess the pharmacological costs of PARP inhibitors (olaparib, niraparib, rucaparib and veliparib) in maintenance treatment after responding to first-line chemotherapy in EOC. Incremental cost-effectiveness ratio (ICER) was calculated as the ratio between the difference of the costs in the intervention and in the control groups (pharmacy costs) and the difference between the effect in the intervention and in the control groups (progression-free survival (PFS)). We have considered the pivotal phase III randomized controlled trials (RCTs). Three different populations were considered: the overall population, patients with germline BRCA mutation (gBRCA) and homologous recombination deficiency (HRD) patients non-gBRCA mutation. Three thousand four hundred and twenty patients and 1209 patients were considered in maintenance treatment after responding to first- and second-line chemotherapy in EOC, respectively. At the actual price, the treatment with PARP inhibitors is not cost-effective in maintenance treatment after responding to first-line and second-line chemotherapy in EOC. A reduction in pharmacological costs is mandatory.

Since their first application in psychiatry seventy years ago, antipsychotic drugs, besides schizophrenia, have been widely used in the treatment of mood disorders. Such an application of antipsychotics is the subject of this narrative review. Antipsychotic drugs can be arbitrarily classified into three generations. First-generation antipsychotics (FGAs), such as phenothiazines and haloperidol, were mainly applied for the treatment of acute mania, as well as psychotic depression when combined with antidepressants. The second-generation, so-called atypical antipsychotics (SGAs), such as clozapine, risperidone, olanzapine, and quetiapine, have antimanic activity and are also effective for the maintenance treatment of bipolar disorder. Additionally, quetiapine exerts therapeutic action in bipolar depression. Third-generation antipsychotics (TGAs) started with aripiprazole, a partial dopamine D2 receptor agonist, followed by brexpiprazole, lurasidone, cariprazine, and lumateperone. Out of these drugs, aripiprazole and cariprazine have antimanic activity, lurasidone, cariprazine, and lumateperone exert a significant antidepressant effect on bipolar depression, while there is evidence for the efficacy of aripiprazole and lurasidone in the prevention of recurrence in bipolar disorder. Therefore, successive generations of antipsychotic drugs present a diverse spectrum for application in mood disorders. Such a pharmacological overlap in the treatment of schizophrenia and bipolar illness stands in contrast to the dichotomous Kraepelinian division of schizophrenia and mood disorders.

Background: Maintenance therapy with the poly (ADP-ribose) polymerase inhibitors (PARPis) for platinum-sensitive recurrent ovarian carcinoma (OC) have proven to be effective compared with placebo. We aimed to evaluate the cost-effectiveness (CE) of maintenance fuzuloparib compared to routine surveillance (RS), niraparib and olaparib for platinum-sensitive recurrent OC from the Chinese healthcare systems. Method: A partitioned survival model with three-state (progression-free, progressed, death) was constructed utilizing TreeAge Pro 2011 software to evaluate the economic value of fuzuloparib, niraparib and olaparib maintenance treatment for platinum-sensitive recurrent OC based on the clinical data derived from FZOCUS-2, ENGOT-OV16/NOVA and ENGOT-Ov21/SOLO2. Transition probabilities were estimated from the reported survival probabilities in those trials. Cost and health preference data were derived from the literature. The quality-adjusted life-years (QALYs) and lifetime costs were measured for this analysis. A 5 years horizon and 5%/year discount rates were used. One-way analysis, and probabilistic sensitivity analysis (PSA) were performed to explore the model uncertainties. Results: Total cost of fuzuloparib, niraparib and olaparib were $31628.10, $48183.48 and $54605.54, whereas they had an incremental cost-utility ratio of $31992.69, $32216.08 and $23359.26 per additional progression-free survival (PFS) QALYs gained compared with RS, relatively. Model showed that maintenance fuzuloparib achieved at least an 85.5% probability of CE at the threshold of $37654.50/QALY. One-way sensitivity analysis revealed that the results were sensitive to the PFS and the price of medicines. Conclusion: Fuzuloparib was less cost-effective for patients with germline BRCA1/2 mutation and platinum-sensitive recurrent OC compared to olaparib, but was superior to niraparib from the Chinese healthcare systems perspective., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nie, Wu, Sun, Ding, Luan and Wu.)

Background and Hypothesis: Although maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced., Study Design: We systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through January 2021 and reviewed randomized controlled trials (RCTs) that reported relapse rates after antipsychotic dose reduction or discontinuation in patients with chronic schizophrenia. We calculated relative risks (RRs) with 95% confidence intervals (CIs) per person-year and sought to identify potential risk factors for relapse. The study is registered with PROSPERO (CRD42017058296)., Study Results: Forty-seven RCTs (54 patient cohorts, 1746 person-years) were included. The RR for psychotic relapse with dose reduction/discontinuation versus maintenance treatment was 2.3 per person-year (95% CI: 1.9 to 2.8). The RR was higher with antipsychotic discontinuation, dose reduction to less than 3-5 mg haloperidol equivalent (HE), or relatively rapid dose reduction (<10 weeks). The RR was lower with long-acting injectable agents versus oral antipsychotic dose reduction. Other factors that increased the risk of psychotic relapse were younger age and short follow-up time., Conclusions: Clinicians should take several risk factors for psychotic relapse into account when considering dose reduction in patients with chronic schizophrenia. Studies of a relatively fast reduction in antipsychotic dose support a minimum dose of 3-5 mg HE. However, if the dose is tapered more gradually, relapses related to medication withdrawal might be avoided, possibly enabling lower-end doses to be achieved., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Platinum-based chemotherapy (PBCT) is the standard first-line treatment for advanced urothelial carcinoma (UC). Potential cross-sensitivity can be hypothesized between platinum drugs and poly-ADP ribose-polymerase (PARP) inhibitors., Objective: To compare maintenance treatment with the PARP inhibitor niraparib plus best supportive care (BSC) versus BSC alone in patients with advanced UC without disease progression after first-line PBCT., Design, Setting, and Participants: Meet-URO12 is a randomized, multicenter, open-label phase 2 trial. Patients with advanced UC, without disease progression after four to six cycles of PBCT, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, were enrolled between August 2019 and March 2021. Randomization was stratified by ECOG performance status (0/1) and response to PBCT (objective response/stable disease)., Intervention: Patients were randomized (2:1) to experimental arm A (niraparib 300 or 200 mg daily according to body weight and baseline platelets, plus BSC) or control arm B (BSC alone)., Outcome Measurements and Statistical Analysis: The primary endpoint was progression-free survival (PFS). The analysis was performed on an intention-to-treat basis. The secondary endpoints reported in this primary analysis are progression-free rate at 6 mo and safety (adverse event rate)., Results and Limitations: Fifty-eight patients were randomized (39 in arm A and 19 in arm B). The median age was 69 yr, ECOG performance status was 0 in 66% and 1 in 34%; and the best response with chemotherapy was objective response in 55% and stable disease in 45%. The median PFS was 2.1 mo in arm A and 2.4 mo in arm B (hazard ratio 0.92; 95% confidence interval 0.49-1.75, p = 0.81). The 6-mo progression-free rates were 28.2% and 26.3%, respectively. The most common adverse events with niraparib were anemia (50%, grade [G]3 11%), thrombocytopenia (37%, G3-4 16%), neutropenia (21%, G3 5%), fatigue (32%, G3 16%), constipation (32%, G3 3%), mucositis (13%, G3 3%), and nausea (13%, G3 3%). The main limitation of the study is the small sample size: in March 2021, approval of maintenance avelumab for the same setting rendered randomization of patients in the control arm to BSC alone unethical, and accrual was stopped prematurely., Conclusions: Addition of maintenance niraparib to BSC after first-line PBCT did not demonstrate a significant improvement in PFS in patients with UC. These results do not support the conduction of a phase 3 trial with single agent niraparib in this population., Patient Summary: In this trial, we tested the efficacy of niraparib as maintenance treatment in patients affected by advanced urothelial cancer after the completion of first-line chemotherapy. We could not demonstrate a significant improvement in progression-free survival with maintenance niraparib., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Mood recurrences in bipolar disorder (BD) are often associated with poor treatment adherence. Despite long-acting injectable antipsychotics (LAIs) may favor treatment compliance, their use in BD is still poorly explored., Methods: This mirror-image study investigated the effect of LAIs initiation on the number of emergency department (ED) visits and days of hospitalization, among individuals with BD from the mental health services of a large area of the Metropolitan City of Milan. The mirror periods were 365 days either side of the LAI initiation. Individual medical records were retrospectively reviewed., Results: Sixty-eight individuals with BD initiating a LAI over the index period were included. We estimated that LAI initiation overall reduced both ED visits (p = 0.002) and days of hospitalization (p < 0.001). This remained true only for those participants who i) continued LAI for the entire 12-month period of observation and ii) were treated with a second-generation antipsychotic LAI. In addition, LAI initiation reduced number of hospitalization days during hypo/manic (p = 0.013), but not depressive (p = 0.641) episodes, as well as compulsory admission days (p = 0.002)., Limitations: Due to the retrospective design, we could not collect systematic information on symptom severity and reasons of LAI discontinuation. Moreover, the limited sample size did not allow us to estimate effectiveness of single LAI agents., Conclusions: Our study provides additional insight on the effectiveness of LAIs in BD, supporting their clinical utility for pragmatic outcomes such as ED visits and hospitalizations. Further longitudinal research is needed to clarify the real-world effectiveness of LAIs for BD clinical management., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Despite the established safety of electroconvulsive therapy (ECT), ECT-related anxiety (ERA) remains one of the most distressing complications of ECT. ERA is reported to diminish during an acute course of ECT, but it was never studied during maintenance ECT (M-ECT). Our aim was to study the trajectories of ERA during M-ECT and how they differ from trajectories during the acute course., Methods: Thirty-nine patients with unipolar or bipolar depression, retained for M-ECT after an acute ECT course, were included. ERA was assessed the morning before each ECT session using the ECT-related Anxiety Questionnaire (ERAQ)., Results: ERA remained stable during M-ECT (RC = -0.05 (SE = 0.06), t(8.35) = -0.86, p = 0.42), while ERA declined significantly during the acute course (RC = -0.85 (SE = 0.30), t(33.6) = -2.81, p = 0.0082). During the acute course, patients with a psychotic depression were more anxious at baseline (t(32)= -2.42, p = 0.02), and showed a significant decline in ERAQ scores (RC = -1.65 (SE = 0.46), t(31.6) = -3.56, p = 0.0012), whereas patients with a non-psychotic depression were less anxious at baseline and retained stable ERAQ scores during the acute course (RC = -0.06 (SE = 0.41), t(32.1) = -0.14, p = 0.89). Whereas a correlation (r = 0.48) was noticed between the decline of depression severity and ERA during the acute course, this was not the case during M-ECT., Conclusion: ERA runs a stable course during M-ECT, after having decreased during the acute course. During the acute course, ERA trajectories differed significantly between patients with a psychotic and non-psychotic depression. Decline of depression severity and ERA are significantly connected during the acute course of ECT. Both depression severity and ERA remain stable during M-ECT., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Urothelial carcinoma (UC) is the ninth most commonly diagnosed cancer worldwide, with a 3.8/1 male to female ratio. Platinum-based chemotherapy is the first line standard of care for fit patients with advanced UC. However, despite a response rate (RR) for approximately half of patients receiving standard chemotherapy, durable responses are rare (median progression-free progression (PFS) around 8 months). Recently, immune checkpoint inhibitors (ICI) have emerged as new therapeutic options. Among them, Avelumab, an anti-PD-L1 antibody, was assessed in maintenance treatment, demonstrating an overall survival improvement in the JAVELIN Bladder-100 phase III trial. These findings led to its approval as first line maintenance therapy for patients with locally advanced or metastatic UC who have not progressed on prior platinum-containing chemotherapy. However, disease progression as best response was noticed for 37% of patients under Avelumab as maintenance treatment. UC has targetable genomic alterations, including DNA damage repair (DDR) alterations. DDR deficiency is known to major sensitivity to both platinum-based chemotherapy and PD-1/PD-L1 blockade and the combination of ICI and PARP inhibitors showed promising results. It therefore warrants to assess the interest of combining ICI plus PARP inhibitors as maintenance treatment in UC patients., Methods: The TALASUR trial is a single-arm multicenter phase 2 study aiming to assess the antitumor activity of the combination of Avelumab with Talazoparib among patients with locally advanced/metastatic UC in maintenance therapy after platinum-based chemotherapy. The primary objective is to determine the efficacy of the combination, assessed through PFS. Secondary objectives are as follows: safety profile of the association, objective response, duration of tumoral response, disease control rate, time to subsequent therapy, quality of life. A blood and tumor collections will be also constituted. Patient will receive the combination therapy of daily oral Talazoparib (1 mg/day) and intra-venous Avelumab 800 mg on days 1 and 15, in a 28-day cycle. Fifty patients will be enrolled., Discussion: Talazoparib with Avelumab combination may have additive activity when administrated jointly. We hypothesize that combination will increase the antitumor activity in UC first line maintenance setting with an acceptable safety profile., Trial Registration: NCT04678362, registered December 21, 2020., Protocol Version:  Version 1.3 dated from 2020 09 11., (© 2022. The Author(s).)

Introduction: Real-world evidence for the effectiveness and safety of golimumab (GLM) in patients with ulcerative colitis (UC) is limited. The aim of this study was to investigate the 52-week effectiveness and safety of GLM treatment for UC., Methods: This prospective, multicentre, post-marketing surveillance study is conducted in 393 patients with UC in Japan (UMIN000027542). Clinical remission (partial Mayo score ≤2), adverse drug reactions (ADRs) and their predictors, and treatment persistence were analysed., Results: The safety analysis sets comprised 391 patients. Patients in clinical remission at baseline were excluded, and 336 were used for effectiveness analysis. Clinical remission was 47.9%, 48.5%, 44.6%, and 39.6% at weeks 6, 22, 36, and 52, respectively, in the intent-to-treat analysis. In biologic-naive patients, clinical remission was slightly higher than that in biologic-experienced patients. At week 52, patients who concomitantly used corticosteroids at baseline showed numerically lower clinical remission rates than non-users of corticosteroids (34.9% vs. 44.5%). Multivariate analysis showed that smoking history ( p = 0.040, odds ratio [OR] = 1.911, 95% confidence interval [CI] 1.030-3.546) was an independent factor associated with clinical remission at week 52. ADRs occurred in 71 patients (18.2%) and included 9 cases of rash. Serious ADRs occurred in 40 patients (10.2%), including 8 cases of UC exacerbation. Additionally, the presence of comorbidities was associated with ADR incidence ( p = 0.010, OR = 2.000, 95% CI: 1.183-3.380)., Conclusion: The real-world effectiveness of GLM treatment was confirmed in biologic-naive and experienced populations. The safety profile of GLM treatment was consistent with previous findings., Competing Interests: Teita Asano, Yoshihito Tanaka, Kanami Sugimoto, and Shinichi Yoshigoe are full-time employees of Janssen Pharmaceutical K.K. Shiro Nakamura has received speaking fees from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K. and served as a consultant for Janssen Pharmaceutical K.K. Yasuo Suzuki has received speaking fees from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., ZERIA Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., received grants/research support from AbbVie GK, EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., and JIMRO Co., Ltd., and served as a consultant for Janssen Pharmaceutical K.K., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background: Multiple myeloma (MM) is a plasma cell malignancy, while MM outcomes have significantly improved due to novel agents and combinations, MM remains an incurable disease. The key goal of treatment in MM is to achieve a maximal response and the subsequent consolidation of response after initial therapy. Many studies analyzed an improved progression-free survival (PFS) following lenalidomide alone maintenance versus placebo or observation after autologous stem cell transplant (ASCT) in patients with NDMM. In the SWOG S0777 clinical trial, patients newly diagnosed with MM (NDMM) without ASCT received lenalidomide plus low-dose dexamethasone (DXM) maintenance until progressive disease, where PFS and overall survival (OS) were significantly improved. In the present study, we assessed the efficacy and toxicity of the different doses of DXM combined with lenalidomide for maintenance treatment of NDMM for transplant noneligible patients in the standard-risk group., Aim: To investigate the efficacy and adverse effects of different administration modes of DXM combined with lenalidomide for maintenance treatment of MM in standard-risk patients ineligible for transplantation., Methods: A total of 96 MM patients were enrolled in this study, among whom 48 patients received maintenance treatment that consisted of oral administration of 25 milligrams (mg) of lenalidomide from days 1-21 and 40 mg of DXM on days 1, 8, 15, and 22 (DXM 40 mg group), repeated every 4 wk. Another group was treated with oral administration of 25 mg of lenalidomide from days 1-21 and 20 mg of DXM on days 1-2, 8-9, 15-16, and 22-23 (DXM 20 mg group), which was also repeated every 4 wk., Results: The median PFS was 37.25 mo in the DXM 40.00 mg group and 38.17 mo in the DXM 20 mg group ( P = 0.171). The median OS was 50.78 mo in the DXM 40 mg group and 51.69 mo in the DXM 20 mg group ( P = 0.171). Fourteen patients in the DXM 40 mg group and 6 patients in the DXM 20 mg group suffered from adverse gastrointestinal reactions after the oral administration of the DXM tablet ( P = 0.044). Ten patients suffered from abnormal glucose tolerance (GTA), impaired fasting glucose (IFG), or diabetes mellitus in the DXM 40 mg group during our observation time compared to 19 patients with GTA, IFG, or DM in the DXM 20 mg group ( P = 0.033). Abnormal β-crosslaps or higher were found in 5 patients in the DXM 40 mg group and 12 patients in the DXM 20 mg group ( P = 0.049). Insomnia or an increase in insomnia compared to the previous condition was evident in 2 patients in the DXM 40 mg group after maintenance treatment for more than 6 mo compared to 11 patients in the DXM 20 mg group ( P = 0.017)., Conclusion: The DXM 40 mg group exhibited efficacy similar to that of the DXM 20 mg group. However, the DXM 40 mg group had significantly decreased toxicity compared with the DXM 20 mg group in the long term., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)