Safety Of Combination Therapy Research Articles

Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials

Abstract Background Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p < 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p < 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p < 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p < 0.000 01] while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p < 0.000 01]. There were no severe adverse events during treatment. Conclusions SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Efficacy and safety of methotrexate plus hydroxychloroquine combination therapy vs. methotrexate monotherapy in the treatment of rheumatoid arthritis: A randomized controlled clinical trial.

To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Tumor necrosis factor inhibitors enhance corticosteroid therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis linked to immune checkpoint inhibitors: a prospective study.

Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients. In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052). Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α. Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.

The efficacy and safety of combined therapy with endobronchial tamponade and bronchial artery embolization for massive hemoptysis

BackgroundMassive hemoptysis is characterized by its life-threatening nature, potentially leading to airway obstruction and asphyxia. The objective of this study was to evaluate the clinical effectiveness of combining endobronchial tamponade with bronchial artery embolization (BAE) in the treatment of massive hemoptysis.MethodsBetween March 2018 and March 2022, a total of 67 patients with massive hemoptysis who underwent BAE were divided into two groups: the combination group (n = 26) and the BAE group (n = 41). Technical and clinical success rates were assessed, and adverse events were monitored following the treatment. Blood gas analysis and coagulation function indicators were collected before and after the treatment, and recurrence and survival rates were recorded during the follow-up period.ResultsAll patients achieved technical success. There were no significant differences in the clinical success rate, recurrence rates at 3 and 6 months, and mortality rates at 3 months, 6 months, and 1 year between the combination group and the BAE group. However, the hemoptysis recurrence rate at 1 year was significantly lower in the combination group compared to the BAE group (15.4% vs. 39.0%, P = 0.039). No serious adverse events were reported in either group. After treatment, the combination group showed higher levels of arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), fibrinogen (FIB), and D-dimer (D-D) compared to the BAE group (P < 0.05). Multivariate regression analysis demonstrated a significant correlation between combined therapy and hemoptysis-free survival.ConclusionCombination therapy, compared to embolization alone, exhibits superior efficacy in improving respiratory function, correcting hypoxia, stopping bleeding, and preventing recurrence. It is considered an effective and safe treatment for massive hemoptysis.

Efficacy and safety of the combination or monotherapy with GLP-1 receptor agonists and SGLT-2 inhibitors in Type 2 diabetes mellitus: An update systematic review and meta-analysis

PurposeTo evaluate the efficacy and safety of combination therapy with sodium-glucose cotransporter2(SGLT-2) inhibitors and glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus (T2DM). MethodsTo construct an exhaustive database of randomized controlled trials (RCTs) concerning SGLT-2 inhibitors and GLP-1 agonists, a methodical search was undertaken across a range of databases, such as Embase, PubMed, and the Cochrane Central Register of Controlled Trials, from their inception to January 2023. Following this, a meta-analysis was executed to amalgamate the collected data, which allowed for the calculation of standardized mean differences (SMDs), odds ratios (ORs), and 95 % confidence intervals (CIs) for a spectrum of outcomes. This analytical approach was designed to yield a quantitative evaluation of the therapeutic efficacy and safety profile of SGLT-2 inhibitors and GLP-1 agonists for the treatment of diabetes mellitus. ResultsWhen compared to GLP-1 agonist therapy alone, the combination therapy did not significantly reduce fasting plasma glucose (FPG) levels (95 % confidence interval [CI]: -0.27, 0.10; p = 0.35), body weight (95 % CI: -0.18, 0.18; p = 1.00), Glycosylated Hemoglobin, Type A1C (HbA1c) (95 % CI: -0.29, 0.07; p = 0.22), or systolic blood pressure (SBP) values (95 % CI: -0.29, 0.06; p = 0.21). In contrast, when compared to SGLT-2 inhibitor therapy alone, combination therapy significantly decreased FPG by 0.24 mmol/L (95 % CI: -0.43, -0.05; p = 0.01), HbA1c by 0.45 % (95 % CI: -0.72, -0.18; p = 0.001), and SBP by 0.12 mmHg (95 % CI: -0.24, 0.00; p = 0.05). However, the combination therapy failed to demonstrate a significant reduction in body weight when compared with either SGLT-2 inhibitor therapy (95 % CI: -0.20, 0.05; p = 0.24) or GLP-1 agonist therapy (95 % CI: -0.18, 0.18; p = 1.00). Additionally, the combination therapy did not increase the incidence of hypoglycemia. It should be noted that data regarding mortality and cardiovascular outcomes were limited. ConclusionsThe combination treatment of SGLT-2 inhibitors and GLP-1 receptor agonists effectively reduces HbA1c, FPG, and SBP without elevating the risk of hypoglycemia when compared to monotherapy with SGLT-2 inhibitors. However, these beneficial effects were not observed when the combination therapy was compared with GLP-1 receptor agonist treatment alone.

Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study

BackgroundIn 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS).MethodsCTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups.ResultsTwenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups.ConclusionsThis study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD.

Efficacy and Safety of Combination Therapy With Vaginal and Urethral Erbium-Doped Yttrium-Aluminum-Garnet (Er:YAG) Laser for Overactive Bladder With Urinary Incontinence.

This retrospective cohort study with propensity score (PS) matching aimed to evaluate the efficacy and safety of a combination therapy with vaginal and urethral erbium:yttrium aluminum garnet laser (VEL+UEL) (SP Dynamis; Fotona d.o.o., Ljubljana, Slovenia) in the treatment of overactive bladder with urinary incontinence (OAB-wet). The study included female OAB-wet patients aged 65 and above who were already taking OAB medication. Data obtained from electronic medical records were subjected to propensity score matching. All patients received instructions on pelvic floor exercises and were prescribed an appropriate dose of OAB medication. The VEL+UEL group (n=30) underwent three monthly laser sessions, while the control group (n=30) did not receive the treatment. Clinical outcomes were evaluated using the Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), three-day urination diary, and Vaginal Health Index Score (VHIS). Medication usage and adverse events were also assessed. Statistical analysis and R code were performed using the AI chatbot GPT-4.0. The VEL+UEL group showed significant improvements in OABSS score, ICIQ-SF score, voided volume, daytime frequency, nocturia, and VHIS after 12 months of treatment (p<0.001). Notably, 13.3% of patients transitioned from OAB-wet to OAB-dry. In contrast, the control group did not exhibit significant changes. Medication use was significantly reduced in the VEL+UEL group compared to the control group (p<0.001). No long-term side effects were reported. Combination therapy with VEL+UEL demonstrated efficacy and safety in the treatment of OAB-wet. Improvements in OAB symptoms, voided volume, frequency, nocturia, and vaginal health were observed, with a subset of patients transitioning to OAB-dry. VEL+UEL therapy offers a potential treatment option for OAB-wet, reducing medication use and improving patient outcomes. Further research is warranted to investigate the mechanism, long-term effects, safety, and cost-effectiveness of VEL+UEL therapy.

Novel Approach: Diphenhydramine and Lidocaine Combination Therapy for Alleviating Inflammatory and Allergic Skin Conditions with Coexisting Itch

Skin inflammatory and allergic conditions often result in symptoms such as erythema, edema, and pruritus, significantly impacting patients' quality of life. Traditional treatment approaches target either the inflammatory or allergic components individually, leaving the accompanying itch inadequately addressed. This study aims to explore the efficacy and safety of a combination therapy using diphenhydramine and lidocaine for managing inflammatory and allergic skin conditions with coexisting itch. Diphenhydramine, a first-generation antihistamine, exhibits potent antiallergic properties by inhibiting histamine receptors (H1). Lidocaine, a local anesthetic, possesses analgesic effects and alleviates pruritus by blocking sensory neurons and reducing capillary permeability. The synergistic effects of diphenhydramine and lidocaine hold promise in providing a comprehensive treatment option for individuals with inflammatory and allergic skin conditions. In this study, the efficacy and safety of combination therapy with diphenhydramine and lidocaine will be evaluated through its effects on symptom relief, inflammatory markers and patient satisfaction. Furthermore, we will analyze dermatoses where the combination therapy used had the best results. The study will also focus on market analysis and formulation availability. This investigation into the diphenhydramine and lidocaine combination therapy represents an innovative approach in dermatology, offering a unique solution for addressing both the underlying inflammation and the troublesome itch associated with inflammatory and allergic skin conditions.

Efficacy and safety of combination therapy with binimetinib, encorafenib, and cetuximab for BRAF non-V600E mutated metastatic colorectal cancer: Results from a phase 2 BIG BANG trial (EPOC1703).

3585 Background: BRAF mutations which are found in 8-12% of metastatic colorectal cancer (mCRC) can be classified into three groups; Class 1 and 2 tumors do not respond to anti-EGFR antibody therapy because of the RAS independent activity, while previous studies suggested potential anti-tumor activity of anti-EGFR antibody for class 3 tumor. Combination therapy with binimetinib, encorafenib, and cetuximab showed the substantial efficacy for BRAF V600E mutated mCRC in the BEACON CRC trial, however, the clinical activity of these triplet therapy for BRAF non-V600E mutated mCRC is unknown. Here, we conducted a multicenter phase 2 trial to assess the efficacy and safety of combination therapy with binimetinib, encorafenib, and cetuximab in patients with BRAF non-V600E mutated mCRC. Methods: We enrolled patients with RAS wild-type and BRAF non-V600E mutated mCRC, refractory or intolerant to at least one fluoropyrimidine-based chemotherapy, and no prior history of anti-EGFR antibody (primary analysis cohort) or refractory to prior anti-EGFR antibody (anti-EGFR antibody refractory cohort). Enrolled patients receive binimetinib (45 mg BID), encorafenib (300 mg QD), and cetuximab (initially 400 mg/m2 and subsequently 250 mg/m2, weekly) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed confirmed objective response rate (ORR) in the primary analysis cohort with sample size of 21 patients. Results: Between May 2018 and March 2023, 12 and 20 patients were enrolled in the primary analysis cohort and the anti-EGFR antibody refractory cohort, respectively (same order in the following abstract). 7 and 19 patients had a history of ≥ 2 lines of previous chemotherapy, respectively. The most frequent mutation overall was BRAF D594G (n=14, 43.8%). There were each 2 responders in both cohorts, resulting in 16.7% (95%CI, 2.1-48.4%) and 10.0% (95%CI, 1.2-31.7%) of confirmed ORR, respectively. Among 7 patients harboring class 1 or 2 tumors in both cohorts combined, there were 2 responders (ORR 28.6%). Median progression-free survival was 3.3 months and 3.0 months, respectively. Grade 3 or higher adverse events occurred in 4 and 10 patients, respectively, and no new safety signals were identified. Conclusions: The combination therapy with binimetinib, encorafenib, and cetuximab showed modest efficacy for BRAF non-V600E mutated mCRC, with a manageable safety profile, although there was not enough statistical power due to slow accrual. Circulating-tumor DNA analyses at the timepoint of before and after treatment are ongoing. Clinical trial information: UMIN000031857. [Table: see text]

Efficacy and safety of combination therapy with envafolimab and lenvatinib in patients with endometrial cancer after failure of first-line platinum-based therapy.

Efficacy and safety of combination therapy with envafolimab and lenvatinib in patients with endometrial cancer after failure of first-line platinum-based therapy.

Efficacy and safety of SBRT combined with sintilimab and IBI305 in patients with advanced HCC and previously failed immunotherapy: study protocol of a phase 2 clinical trial

IntroductionHepatocellular carcinoma (HCC) is a leading cause of cancer-related death in China. The combination of immune checkpoint inhibitors (ICIs) and antiangiogenic drugs, such as bevacizumab and tyrosine kinase inhibitors, has...

Efficacy and safety of various drug combinations in treating plaque Psoriasis: A meta-analysis

Background Psoriasis, a chronic inflammatory disease affecting the skin, joints, and nails (2-3% worldwide), significantly affects quality of life. Genetic and environmental factors also play key roles. Topical corticosteroids, calcineurin inhibitors, and oral corticosteroids help to manage plaque psoriasis symptoms, but combination therapies might offer greater effectiveness and improved safety profiles. These combinations could potentially reduce medication dosages and side effects in patients. Objective To assess the efficacy and safety of various drug combinations over conventional monotherapies in the treatment of moderate to severe plaque psoriasis, which incorporates palmoplantar psoriasis and psoriasis vulgaris, by discovering and utilizing research articles comprising the same or similar variables as PASI 75 and evaluating the information using RevMan v5.4.1. Method We reviewed the efficacy and safety of combination therapy vs. monotherapy/placebo for moderate-to-severe plaque psoriasis (palmoplantar and vulgaris) using PASI 75 via RevMan v5.4.1. Risk of bias assessment and funnel plots were employed to assess the heterogeneity of each paper. Inclusion criteria – Publications &lt; 20yrs, RCTs, plaque/palmoplantar/psoriasis vulgaris; exclusion criteria – Guttate/arthritic psoriasis, pediatric and pregnant individuals, publications &gt; 20 yrs. Results Seventeen studies were analyzed, comprising a total of 2291 patients (n=1147 with combination regimens and n=1144 with control regimen in the analysis). A significant PASI 75- response was observed in the pioglitazone combination subgroup as compared to placebo (OR=4.92,95% CI 2.19-11.05, P = 0.0001); methotrexate combination subgroup as compared to placebo (OR=2.56, 95% CI 1.67-3.94, P&lt; 0.0001) test of subgroup differences showed P= 0.14, I2= 34%. Incidence rate of abnormality in levels of liver enzymes (OR=1.89,9.5% CI 6.69-5.22, P=0.22), nausea (OR=1.28,95% CI 0.77-2.14, P=0.34), headache (OR=1.28,95% CI 0.77-2.14, P=0.58), fatigue (OR=0.89, 95% CI 0.41-1.90, P=0.45).] Conclusion This study showed that combination therapy is very effective for plaque psoriasis, with promising combinations of pioglitazone. While safety seems similar between the groups, larger studies are needed to determine the long-term effects. These findings suggest that personalized treatment plans could improve outcomes; however, confirmation through larger trials is crucial before wider use. This opens doors to research on optimal combinations for individual patients.

Adding Letrozole to Growth Hormone and Gonadotropin-Releasing Hormone Analog Increases Height in Girls With Short Stature: A Hospital Record–Based Retrospective Study

ObjectiveThere have been rare data on letrozole for height improvement in girls. This study aimed to clarify the efficacy and safety of combination therapy with recombinant human growth hormone (rhGH), GnRHa, and letrozole in improving the height of girls with short stature and advanced bone age. MethodsThis was a hospital record–based retrospective study. Follow-up was conducted on girls with short stature who received treatment with rhGH, GnRHa, and letrozole in our hospital. The treatment group included a total of 29 participants. Before treatment, the mean age of the patients was 11.17 years, and the mean treatment duration was 17.31 months. The control group consisted of 29 short-statured girls who received rhGH/GnRHa treatment, with the mean age and treatment duration of 12.43 years and 16.59 months, respectively. ResultsThe predicted adult heights (PAHs) before and after treatment were 155.38 and 161.32 cm (P < .001). The ΔPAH in the treatment group was 4 cm higher than that in the control group (5.85 vs 1.82 cm, P < .001). Significant differences were noted in the height standard deviation scores of bone age (P < .001) and chronological age (P = .003) before and after treatment. There was an increasing body mass index during therapy (P = .039). The height gain was 8.71 ± 4.46 cm, and the growth rate was 6.78 ± 3.84 cm per year. ConclusionCombined treatment with GH, GnRHa, and letrozole can enhance the adult height and PAH in short-statured girls, and no significant side effects have been reported.

Abstract PO2-05-12: Retrospective analysis on therapeutic efficacy and predictive indicators of eribulin plus anti-angiogenic drugs for metastatic breast cancer

Abstract Background: Eribulin has been widely used for the treatment of metastatic breast cancer (MBC). It has been found that eribulin can work in synergy with Bevacizumab or Anlotinib to achieve anti-angiogenic effects and possible synergistic enhancement. To optimize the efficacy of eribulin usage in late-line MBC patients, it is essential to delve deeper into the effects of combined treatments and gather more real-world clinical outcomes. Therefore, we evaluated the efficacy and safety of eribulin plus the anti-angiogenic drugs in late-line MBC patients. Objective: This study aims to retrospectively analyze the therapeutic efficacy and safety of eribulin plus anti-angiogenic drugs in treating metastatic breast cancer and explore predictive indicators of the therapeutic efficacy of eribulin in treating MBC. Methods: A retrospective review study was performed. 40 Patients diagnosed with MBC and treated with eribulin in Xi’an international medical center hospital from May 2020 to May 2021 were enrolled in this study. Patients were evaluable for this study and divided into two groups based on whether they received eribulin monotherapy or combined therapy. 22 patients were treated with eribulin monotherapy, and 18 were treated with eribulin and anti-angiogenic drugs (Bevacizumab and Anlotinib). Patients’ treatment parameters and characteristics were recorded. The Kaplan-Meier method was used to calculate the median PFS and corresponding 95% confidence interval (CI), and the Cox regression model was used for multivariate analysis of predictive indicators. The Fisher exact probability test was used to compare the difference in adverse reactions between the two groups, with a level of significance set at p-value &amp;lt; 0.05. Results: All study patients have an average of 5 treatment lines and a median progression-free survival (mPFS) of 4.2 months. The eribulin plus anti-angiogenic drug treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic drug treatment (7.0 months vs 2.0 months, p &amp;lt; 0.001, log-rank). Multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxanes was predictive of shorter PFS (HR = 4.583, p = 0.019). Other factors, including age, Eastern Cooperative Oncology Group (ECOG) performance status, hormone receptor (HR) type, expression status, human epidermal growth factor receptor-2 (HER-2) expression status, Ki-67 level, number of metastatic lesions, and number of prior lines of Eribulin therapy, were not significantly associated with PFS. The results of Fisher’s exact test show that there was no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic drugs. Conclusion: A combination of eribulin and anti-angiogenic therapy has significantly prolonged mPFS in the treatment of MBC patients. Other factors such as prior non-taxane resistance, grade 3-4 neutropenia occurrence after treatment, and combined anti-angiogenic therapy can be used as biomarkers for predicting treatment efficacy. The adverse events are manageable and the safety of combined therapy can be guaranteed. Therefore, the eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. Keywords: metastatic breast cancer, eribulin, anti-angiogenic therapy, retrospective analysis Citation Format: Junmei Zhang, Xuezheng Wang, Hongjuan Du, Yan Xue. Retrospective analysis on therapeutic efficacy and predictive indicators of eribulin plus anti-angiogenic drugs for metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-12.

Efficacy and safety of combination therapy (desmopressin with tolterodine) in nocturnal enuresis in children: An institutional experience

ABSTRACT Background: Nocturnal enuresis is one of the most common problems of childhood. Desmopressin is started as a first-line treatment along with essential behavioral therapy like fluid restriction before bed and sleep hygiene. Given the high relapse rates seen with using desmopressin alone, the need of the hour is to reinforce its effects using another agent so that the remission is long-lasting. Aim: The aim is to look for efficacy and safety of treatment using combination therapy of desmopressin with tolterodine in nocturnal enuresis and further to look for the relapse rate with a structured withdrawal regimen. Results: A total of 150 patients of nocturnal enuresis were included in the study. Ninety patients (75%) were males, and 30 patients (25%) were females. The median age of patients was 12 years. Evaluation of the consequences at 1 month, 3 months, and 6 months revealed complete remission in 87 patients (72.5%), 105 patients (87.5%), and 105 patients (87.5%), respectively. After 12 months with desmopressin + tolterodine, it was found that 99 patients (82.5%) had complete remission, six patients (5%) had a relapse, and 12.5% of individuals still suffered from enuresis. The relapse rate on follow-up of 6 months after complete cessation of the treatment of 120 patients was 5% in combination therapy. The complication rate with combination therapy is 4.17%. There is no significant effect of gender or age on improvement with combination therapy. Conclusion: Desmopressin given in combination with tolterodine is safe and effective as combination therapy for treating nocturnal enuresis, and in most cases, long-term remissions can be achieved.

Efficacy and Safety of Combination Therapy with Low-Dose Rivaroxaban in Patients with Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: To review the evidence on the effectiveness and safety of low-dose-rivaroxaban 2.5 mg twice daily (LDR) in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) taking antiplatelets. Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Efficacy endpoints were cardiovascular events (CVEs), myocardial infarction, stroke, all-cause, and cardiovascular death. Any, major, fatal bleeding, and intracranial hemorrhage (ICH) were safety endpoints. Numbers needed to treat (NNT), and numbers needed to harm (NNH) were also calculated. Results: Seven RCTs were included with 45,836 patients: 34,276 with CAD and 11,560 with PAD. Overall, 4247 CVEs and 3082 bleedings were registered. LDR in association with either any antiplatelet drug or aspirin (ASA) alone reduced the risk of CVEs (hazard ratio [HR] 0.86, 95% confidence interval [95%CI] 0.78-0.94) and ischemic stroke (HR 0.68, 95%CI 0.55-0.84). LDR + ASA increased the risk of major bleeding (HR 1.71, 95%CI 1.38-2.11) but no excess of fatal bleeding or ICH was found. The NNT to prevent one CVE for LDR + ASA was 63 (43-103) and the NNH to cause major bleeding was 107 (77-193). Conclusions: The combination of LDR with either antiplatelet drugs or low-dose aspirin reduces CVEs and ischemic stroke in patients with CAD/PAD. There was an increased risk of major bleeding but no excess of fatal or ICH was found. LDR seems to have a favorable net clinical benefit compared to ASA treatment alone.

The abscopal effect: mechanism of occurrence and prospects of using it in therapy of metastatic cancer

The abscopal effect in oncology has been known for 70 years, but until recently its clinical significance was rather low. The development of immune response checkpoint inhibitors has led to an active study of this phenomenon. There is now evidence of improved survival among patients, in whom the abscopal effect has been documented, opening new perspectives for the treatment of cancers at different stages. This review presents data on the mechanisms of the abscopal effect, experimental and clinical data, current limitations and possible perspectives. The aim of the study was to investigate the current concept of the abscopal effect occurrence and to evaluate the prospects of using the abscopal effect in therapy of metastatic cancer. Material and Methods. We searched publications in Pubmed system from 2010 to 2023. Of 286 publications, 72 were used for writing the review. Results. In the era of widespread use of immune checkpoint inhibitors (ICIs) for cancer therapy, the abscopal effect appears to be an effective therapeutic approach with broad prospects of application in the treatment of patients with metastatic cancer. Conclusion. The incidence of the abscopal effect has increased with the advent of immune therapy, and the use of ICIs with radiation therapy (RT) has shown improved survival even in patients with advanced disease. More research is needed to establish standardized treatment protocols, including the optimal dose and timing of RT, as well as the efficacy and safety of combination therapy with different classes of ICIs. Further search for clinical and laboratory abscopal effect predictors, which could allow personalized treatment approaches, is required.

Efficacy and safety of VEGF/VEGFR inhibitors for platinum-resistant ovarian cancer: a systematic review and meta-analysis of randomized controlled trials

BackgroundAlmost all patients with ovarian cancer will experience relapse and eventually develop platinum-resistant. The poor prognosis and limited treatment options have prompted the search for novel approaches in managing platinum-resistant ovarian cancer (PROC). Therefore, a meta-analysis was conducted to evaluate the efficacy and safety of combination therapy with vascular endothelial growth factor (VEGF) /VEGF receptor (VEGFR) inhibitors for PROC.MethodsA comprehensive search of online databases was conducted to identify randomized clinical trials published until December 31, 2022. Pooled hazard ratios (HR) was calculated for overall survival (OS) and progression-free survival (PFS), while pooled odds ratio (OR) was calculated for objective response rate (ORR) and treatment-related adverse events (TRAEs). Subgroup analysis was further performed to investigate the source of heterogeneity.ResultsIn total, 1097 patients from eight randomized clinical trials were included in this meta-analysis. The pooled HRs of OS (HR = 0.72; 95% CI: 0.62–0.84, p < 0.0001) and PFS (HR = 0.52; 95% CI: 0.45–0.59, p < 0.0001) demonstrated a significant prolongation in the combination group compared to chemotherapy alone for PROC. In addition, combination therapy demonstrated a superior ORR compared to monotherapy (OR = 2.34; 95%CI: 1.27–4.32, p < 0.0001). Subgroup analysis indicated that the combination treatment of VEGF/VEGFR inhibitors and chemotherapy was significantly more effective than monochemotherapy in terms of OS (HR = 0.71; 95% CI: 0.61–0.84, p < 0.0001), PFS (HR = 0.49; 95% CI: 0.42–0.57, p < 0.0001), and ORR (OR = 2.97; 95% CI: 1.89–4.67, p < 0.0001). Although the combination therapy was associated with higher incidences of hypertension, mucositis, proteinuria, diarrhea, and hand-foot syndrome compared to monochemotherapy, these toxicities were manageable and well-tolerated.ConclusionsThe meta-analysis demonstrated that combination therapy with VEGF/VEGFR inhibitors yielded better clinical outcomes for patients with PROC compared to monochemotherapy, especially when combined with chemotherapy. This analysis provides more treatment options for patients with PROC.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO], Prospective Register of Systematic Reviews (PROSPERO), identifier: CRD42023402050.

Efficacy and safety of combination therapy with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis.

Background: Recent studies have suggested that combination therapy with pirfenidone and nintedanib is safe and tolerable in patients with idiopathic pulmonary fibrosis (IPF). However, data from real-world practice are limited. Thus, we aimed to investigate the safety and efficacy of this combination therapy in patients with IPF in a real-world setting. Methods: A multicenter retrospective cohort study was conducted to investigate the safety and efficacy of combination therapy with pirfenidone and nintedanib in 45 patients with IPF. Incidences of adverse events and rates of lung function decline were compared before and after the combination therapy. Propensity score matching was performed to compare the outcomes between the combination and monotherapy groups. Results: The mean age of the patients was 68.8years, and 82.2% of them were male. The median follow-up duration after combination therapy was 12.1months. The majority of the patients (97.8%) received nintedanib as an add-on to pirfenidone. The most common adverse events after the combination therapy were diarrhea and anorexia. Pirfenidone or nintedanib was stopped in 12 patients owing to gastrointestinal AEs, lung transplantation, or financial problems. In patients with serial lung function data, the rate of decline in the forced vital capacity was significantly reduced after the combination therapy. In the matched analysis, the combination group had a higher incidence of diarrhea than the monotherapy group without an increase in serious adverse events; however, the two groups had similar changes in forced vital capacity (FVC). Conclusion: The combination of pirfenidone and nintedanib in patients with IPF has the potential to reduce the rate of FVC decline. However, in the matched analysis, FVC decline was comparable between the patients on combination therapy and those on monotherapy. The incidence of certain adverse events, particularly diarrhea, was higher with combination therapy, but serious adverse events were similar between the groups.

Effect of Hetrombopag Combined with Rhtpo in Patients with Severe Immune Thrombocytopenia

Background: Severe Immune Thrombocytopenia (ITP) is a life-threatening acquired hemorrhagic disease with dramatically decreased platelet number and clinical bleeding symptoms. Some patients with severe ITP did not respond to first-line treatment including steroids and Intravenous Immunoglobulin (IVIG). It was critical for them to use effective treatments to promote platelet and reduce the risk of fatal bleeding. Clinical practice guidelines have recommended the use of thrombopoietin receptor agonist (TPO-RA) as a second-line treatment for ITP. Recombinant human thrombopoietin (rhTPO) and hetrombopag are two distinct TPO-RAs with different mechanisms. As reported, there remains no study assessing the efficacy and safety of hetrombopag combined with rhTPO in the treatment of ITP. Therefore, the present study aimed to investigate the efficacy of hetrombopag plus rhTPO in Chinese patients with severe ITP, focusing on the short rather than the long-term efficacy, such as quickly increasing platelet count and significantly reducing bleeding, which would be more meaningful for severe patients whose platelet count &amp;lt;10 × 10 9/L. Methods: This was a prospective, open-label, single-center study with a planned enrollment of 30 patients. The inclusion criteria were patients ≥ 18 years, diagnosed with primary immune thrombocytopenia, platelet count &amp;lt;10 × 10 9/L, or bleeding score ≥ 5. Patients receiving other ITP drugs as maintenance therapy were eligible if previous glucocorticoid therapy doses were stable, and rituximab was used for at least 2 months and other immunosuppressants were stable for at least 4 weeks. Patients who had received IVIG, avatrombopag, eltrombopag, or romiplostim within 2 weeks prior to enrollment were excluded. Histories of platelet transfusion one week before treatment were excluded. Hetrombopag was given at 5 mg/day for 28 days, while rhTPO was administered at 300 U/kg subcutaneously daily for 14 days. When PLT &amp;gt; 100 × 10 9/L, rhTPO should be discontinued. When PLT &amp;gt; 150 × 10 9/L, the dosage of hetrombopag was reduced to 2.5mg/day, and it would be discontinued if PLT &amp;gt; 250 × 10 9/L. The primary endpoints were proportion of subjects with platelet count ≥30×10 9/L and at least doubled the baseline platelet count within 28 days. Secondary endpoints included bleeding score, incidence of thrombotic events, and adverse events (AEs). Results: As to July 27, 2023, a total of 20 patients were included in this study, with a median age of 36 years and a male proportion of 50%. Among them, 70% (14 cases) were newly diagnosed ITP patients. 50% of patients have received ≥ 1 line of previous treatment, of which 2 patients have received IVIG treatment and both have achieved CR (PLT ≥ 100 × 10 9/L). The baseline median platelet count was 5 × 10 9/L, and 95% (19 cases) of patients had active bleeding with a bleeding score of ≥ 1 point. The median duration for hetrombopag at dose of 5mg is 8.0 days, and rhTPO is 6.5 days. After combined treatment, the median time for platelet counts reached 30, 50, and 100 × 10 9/L was 4.5 days, 6 days, and 7 days, respectively. Among them, the median platelet count reached 103 × 10 9/L after 7 days treatment and 214.5 × 10 9/L after 15 days. Within 15 days of combined treatment, 15% (3 cases) of patients achieved partial platelet reaction (PLT &amp;gt; 50 × 10 9/L, without bleeding), and 85% (17 cases) achieved complete platelet reaction (PLT &amp;gt; 100 × 10 9/L, without bleeding). In terms of safety, two patients experienced liver function abnormalities, both of which were grade 1-2. One was related to treatment drugs, and the other was associated with underlying autoimmune liver disease. No thrombotic events occurred in all patients. Conclusion: This study innovatively explores the efficacy and safety of combination therapy with hetrombopag and rhTPO in the treatment of severe ITP. It is preliminarily confirmed that this combination therapy can effectively and quickly improve the early platelet response of ITP patients, avoid bleeding damage, and is expected to become a new treatment choice for severe ITP patients. We also look forward to the overall efficacy evaluation results of all patients after completing treatment in the future.