Efficacy and safety of corticosteroids in the management of chronic rhinosinusitis: A systematic review and meta-analysis of randomized and non-randomized studies

Chronic rhinosinusitis (CRS) refers to inflammation of the nasal sinuses and mucosa, with persistence of sinus inflammation and clinical manifestations beyond 12 weeks1 . CRS affects between 6 and 12% of adults, and is a cause of reduced quality of life (QoL), and high healthcare costs2 . Management has consisted of topical and systemic glucocorticoids, antibiotics and often repeated sinus surgery. Over the past 20 years biologic therapies under investigation for asthma, with overlapping nasal polyposis have showed significant improvement in sinonasal CRS symptoms and reduced nasal polyp swelling3 .

This living systematic review is one of several Cochrane Reviews evaluating the medical management of patients with chronic rhinosinusitis. Chronic rhinosinusitis is common. Itis characterised by inflammation of the nasal and sinus linings,nasal blockage, rhinorrhoea, facial pressure/pain and loss of sense of smell. It occurs with or without nasal polyps. 'Biologics' are medicinal products produced by a biological process.Monoclonal antibodies are one type, already evaluated in other inflammatory conditions (e.g.asthma and atopic dermatitis). To assess the effects of biologics for the treatment of chronic rhinosinusitis. The Cochrane ENT Information Specialist searched the Cochrane ENT Register; CENTRAL (2020, Issue 9); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 28 September 2020. Randomised controlled trials (RCTs) with at least three months follow-upcomparing biologics (monoclonal antibodies) against placebo/no treatment in patients with chronic rhinosinusitis. We used standard Cochrane methodological procedures. Our primary outcomes were disease-specific health-related quality of life (HRQL), disease severity and serious adverse events (SAEs). The secondary outcomes were avoidance of surgery, extent of disease (measured by endoscopic or computerised tomography (CT) score), generic HRQL and adverse effects (nasopharyngitis, including sore throat). We used GRADE to assess the certainty of the evidence for each outcome. We included 10 studies. Of 1262 adult participants, 1260 had severe chronic rhinosinusitis with nasal polyps; 43% to 100% ofparticipants also had asthma. Three biologics, with different targets, were evaluated: dupilumab, mepolizumab and omalizumab. All of the studies were sponsored or supported by industry. For this update (2021) we have included two new studies, including 265 participants, which reported data relating to omalizumab. Anti-IL-4Rα mAb (dupilumab)versus placebo/no treatment (all receiving intranasal steroids) Three studies (784 participants) evaluated dupilumab. Disease-specific HRQL wasmeasured with the SNOT-22 (a 22-item questionnaire, with a score range of 0 to 110;minimal clinically important difference (MCID) 8.9 points). At 24 weeks, dupilumab results in a large reduction (improvement) in the SNOT-22 score (mean difference (MD) -19.61, 95% confidence interval (CI) -22.54 to -16.69; 3 studies; 784 participants; high certainty). At between 16 and 52 weeks of follow-up, dupilumab probably results in a large reduction in disease severity, as measured by a 0- to 10-point visual analogue scale (VAS) (MD -3.00, 95% CI -3.47 to -2.53; 3 studies; 784 participants; moderate certainty). This is a global symptom score, including all aspects of chronic rhinosinusitis symptoms. At between 16 and 52 weeks of follow-up, dupilumab may result in a reduction in serious adverse events compared to placebo (5.9% versus 12.5%, risk ratio (RR) 0.47, 95% CI 0.29 to 0.76; 3 studies, 782 participants; low certainty). Anti-IL-5 mAb (mepolizumab)versus placebo/no treatment (all receiving intranasal steroids) Two studies (137 participants) evaluated mepolizumab. Disease-specific HRQLwas measured with the SNOT-22. At 25 weeks, the SNOT-22 score may be reduced (improved) in participants receivingmepolizumab (MD -13.26 points, 95% CI -22.08to -4.44; 1 study; 105 participants; low certainty; MCID 8.9). It is very uncertain whether there is a difference in disease severity at 25 weeks:ona 0- to 10-point VAS, disease severity was -2.03 lower in those receiving mepolizumab(95% CI -3.65 to -0.41; 1 study;72 participants; very low certainty). It is very uncertain if there is a difference in the number of serious adverse events at between 25 and 40 weeks (1.4% versus 0%; RR 1.57, 95% CI 0.07 to 35.46; 2 studies; 135 participants, very low certainty). Anti-IgE mAb (omalizumab)versus placebo/no treatment (all receivingintranasal steroids) Five studies (329 participants) evaluated omalizumab. Disease-specific HRQL was measured with the SNOT-22. At 24 weeks omalizumab probably results in a large reduction in SNOT-22 score (MD -15.62, 95% CI -19.79 to -11.45; 2 studies; 265 participants; moderate certainty; MCID 8.9). We did not identify any evidence for overall disease severity. It is very uncertain whether omalizumab affects the number of serious adverse events, with follow-up between 20 and 26 weeks (0.8% versus 2.5%, RR 0.32, 95% CI 0.05 to 2.00; 5 studies; 329 participants; very low certainty). Almost all of the participants in the included studies had nasal polyps (99.8%) and all were using topical nasal steroids for their chronic rhinosinusitis symptoms. Inthese patients, dupilumab improves disease-specific HRQL compared to placebo. It probably also results in a reduction in disease severity, and may result in a reduction in the number of serious adverse events. Mepolizumab may improve disease-specific HRQL.Itis very uncertain if there is a difference in disease severity or the number of serious adverse events. Omalizumab probably improves disease-specific HRQL compared to placebo. It is very uncertain if there is a difference in the number of serious adverse events. There was no evidence regarding the effect of omalizumab on disease severity (using global scores that address all symptoms of chronic rhinosinusitis).

Background: Aldosterone synthase inhibitors (ASIs) are a novel class targeting aldosterone biosynthesis, offering a mechanistically distinct approach from mineralocorticoid receptor antagonists. Research Question: Do ASIs significantly reduce blood pressure compared to placebo in patients with hypertension, and what is their associated safety profile? Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating ASIs versus placebo in hypertensive patients. A comprehensive search was performed in Cochrane CENTRAL, PubMed, Scopus, and Web of Science up to April 15, 2025. All available dosages of each agent were pooled into a single treatment node. The primary efficacy outcome was the change in mean seated systolic blood pressure (SBP), while the safety outcome was hyperkalemia. Secondary outcomes included changes in mean seated diastolic blood pressure (DBP), 24-hour ambulatory SBP, serious adverse events (SAEs), and hyponatremia. Data were synthesized using inverse-variance random-effects models. Results: Six RCTs comprising 1,382 participants were included from an initial screening of 855 records. Compared with placebo, ASIs significantly reduced mean seated SBP (mean difference [MD] −6.44 mmHg; 95% CI −8.7 to −4.17; I 2 =0%; p<0.0001). Mean seated DBP was also significantly reduced (MD −2.15 mmHg; 95% CI −3.48 to −0.82; p=0.0015), as was 24-hour ambulatory SBP (MD −6.82 mmHg; 95% CI −8.81 to −4.84; p<0.001). These SBP and DBP reductions were consistent across hypertension subtypes (primary, resistant, and uncontrolled) and among different ASI agents (p for interaction >0.1). The risk of hyperkalemia was significantly elevated (RR 4.48; 95% CI 1.44 to 13.91), primarily driven by lorundrostat (RR 6.96; 95% CI 1.39 to 34.87). However, ASIs were not associated with a significant increase in SAEs (RR: 2.11; 95% CI 0.82 to 5.43; p=0.62) or non-SAEs (RR 1.10; 95% CI 0.76 to 1.57; p=0.62) compared to placebo. No significant increase was observed in hyponatremia risk (RR 1.24; 95% CI 0.34 to 4.46). Conclusions: ASIs significantly and mildly reduced both SBP and DBP in hypertensive patients, with an overall manageable safety profile. The increased risk of hyperkalemia—particularly with lorundrostat—warrants monitoring. These agents may hold promise for enhanced efficacy when combined with other antihypertensive therapies in future trials.

Multiple systemic treatments are available for metastatic castration-sensitive prostate cancer (mCSPC), with unclear comparative effectiveness and safety and widely varied costs. To compare the effectiveness and safety determined in randomized clinical trials of systemic treatments for mCSPC. Bibliographic databases (MEDLINE, Embase, and Cochrane Central), regulatory documents (US Food and Drug Administration and European Medicines Agency), and trial registries (ClinicalTrials.gov and European Union clinical trials register) were searched from inception through November 5, 2019. Eligible studies were randomized clinical trials evaluating the addition of docetaxel, abiraterone acetate, apalutamide, or enzalutamide to androgen-deprivation therapy (ADT) for treatment of mCSPC. Two investigators independently performed screening. Discrepancies were resolved through consensus. A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects of competing treatments were assessed by bayesian network meta-analysis and survival models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. Overall survival, radiographic progression-free survival, and serious adverse events (SAEs). Seven trials with 7287 patients comparing 6 treatments (abiraterone acetate, apalutamide, docetaxel, enzalutamide, standard nonsteroidal antiandrogen, and placebo/no treatment) were identified. Ordered from the most to the least effective determined by results of clinical trials, treatments associated with improved overall survival when added to ADT included abiraterone acetate (hazard ratio [HR], 0.61; 95% credible interval [CI], 0.54-0.70), apalutamide (HR, 0.67; 95% CI, 0.51-0.89), and docetaxel (HR, 0.79; 95% CI, 0.71-0.89); treatments associated with improved radiographic progression-free survival when added to ADT included enzalutamide (HR, 0.39; 95% CI, 0.30-0.50), apalutamide (HR, 0.48; 95% CI, 0.39-0.60), abiraterone acetate (HR, 0.51; 95% CI, 0.45-0.58), and docetaxel (HR, 0.67; 95% CI 0.60-0.74). Docetaxel was associated with substantially increased SAEs (odds ratio, 23.72; 95% CI, 13.37-45.15), abiraterone acetate with slightly increased SAEs (odds ratio, 1.42; 95% CI, 1.10-1.83), and other treatments with no significant increase in SAEs. Risk of bias was noted for 4 trials with open-label design, 3 trials with missing data, and 2 trials with potential unprespecified analyses. In this network meta-analysis, as add-on treatments to ADT, abiraterone acetate and apalutamide may provide the largest overall survival benefits with relatively low SAE risks. Although enzalutamide may improve radiographic progression-free survival to the greatest extent, longer follow-up is needed to examine the overall survival benefits associated with enzalutamide.

Biologics for chronic rhinosinusitis.

Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients with Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial.

Multimodal postoperative analgesia is widely used but lacks evidence of benefit. Investigate beneficial and harmful effects of 4 nonopioid analgesics regimens. Randomized, blinded, placebo-controlled, 4-group trial in 6 Danish hospitals with 90-day follow-up that included 556 patients undergoing total hip arthroplasty (THA) from December 2015 to October 2017. Final date of follow-up was January 1, 2018. Participants were randomized to receive paracetamol (acetaminophen) 1000 mg plus ibuprofen 400 mg (n = 136; PCM + IBU), paracetamol 1000 mg plus matched placebo (n = 142; PCM), ibuprofen 400 mg plus matched placebo (n = 141; IBU), or half-strength paracetamol 500 mg plus ibuprofen 200 mg (n = 140; HS-PCM + IBU) orally every 6 hours for 24 hours postoperatively, starting 1 hour before surgery. Two co-primary outcomes: 24-hour morphine consumption using patient-controlled analgesia in pairwise comparisons between the 4 groups (multiplicity-adjusted thresholds for statistical significance, P < .0042; minimal clinically important difference, 10 mg), and proportion of patients with 1 or more serious adverse events (SAEs) within 90 days (multiplicity-adjusted thresholds for statistical significance, P < .025). Among 559 randomized participants (mean age, 67 years; 277 [50%] women), 556 (99.5%) completed the trial and were included in the analysis. Median 24-hour morphine consumption was 20 mg (99.6% CI, 0-148) in the PCM + IBU group, 36 mg (99.6% CI, 0-166) for PCM alone, 26 mg (99.6% CI, 2-139) for IBU alone, and 28 mg (99.6% CI, 2-145) for HS-PCM + IBU. The median difference in morphine consumption between the PCM + IBU group vs PCM alone was 16 mg (99.6% CI, 6.5 to 24; P < .001); for the PCM-alone group vs HS-PCM + IBU, 8 mg (99.6% CI, -1 to 14; P = .001); and for the PCM + IBU group vs IBU alone, 6 mg (99.6% CI, -2 to 16; P = .002). The difference in morphine consumption was not statistically significant for the PCM + IBU group vs HS-PCM + IBU (8 mg [99.6% CI, -2 to 16]; P = .005) or for the PCM-alone group vs IBU alone (10 mg [99.6% CI, -2 to 16]; P = .004) after adjustment for multiple comparisons and 2 co-primary outcomes. There was no significant difference between the IBU-alone group vs HS-PCM + IBU (2 mg [99.6% CI, -10 to 7]; P = .81). The proportion of patients with SAEs in groups receiving IBU was 15%, and in the PCM-alone group, was 11%. The relative risk of SAE was 1.44 (97.5% CI, 0.79 to 2.64; P = .18). Among patients undergoing THA, paracetamol plus ibuprofen significantly reduced morphine consumption compared with paracetamol alone in the first 24 hours after surgery; there was no statistically significant increase in SAEs in the pooled groups receiving ibuprofen alone vs with paracetamol alone. However, the combination did not result in a clinically important improvement over ibuprofen alone, suggesting that ibuprofen alone may be a reasonable option for early postoperative oral analgesia. ClinicalTrials.gov Identifier: NCT02571361.

PurposeRapid drug desensitization is known to be a good strategy in patients with drug hypersensitivity to chemotherapy. However, changes in maximal drug concentration and exposure time in blood through desensitization may alter other adverse reactions and efficacy of the drug. We investigated rapid desensitization for carboplatin in terms of severe adverse drug reactions (ADRs) and efficacy compared with the standard infusion.MethodsA retrospective cohort study was conducted on patients with recurrent ovarian cancer who received carboplatin chemotherapy from 2017 to 2019. We compared serious adverse events (SAEs), ADRs according to organ classes, time to progression (TTP), and overall survival (OS).ResultsOf 108 desensitization procedures performed in 21 patients, 104 were successfully accomplished (96.3%). There were compared with 271 procedures in 41 patients who received the standard infusion method. There were 8 (7.7%) SAEs in the rapid desensitization group and 34 (12.5%) in the control group. One drug-related death occurred in the rapid desensitization group. In the rapid desensitized group, except for neutropenia, there was no statistically significant increase in SAEs and over grade 3 of ADRs according to organ classes compared with the control group. In the efficacy analysis, TTP and OS were similar in the 2 groups.ConclusionsRapid desensitization of carboplatin can lower the risk of immediate hypersensitivity reactions without changing the inherent effect and severe ADRs.

The aim is to showcase the effectiveness and safety of bosentan or ambrisentan in individuals diagnosed with idiopathic pulmonary fibrosis (IPF) and offer fresh evidence for the management of this condition. For this research, we conducted a meta-analysis of randomized controlled trials by searching various databases, including the Cochrane Library, Excerpta Medica Database, PubMed, and Web of Science. The retrieval was conducted until November 2021. We analyzed the variances in 6-minute walk distance (6MWD), death, diffusion capacity for carbon monoxide (DLCO), forced vital capacity (FVC), hospitalization, IPF worsening, mean pulmonary arterial pressure, serious adverse events (SAEs), Short Form-36 improved, and St. George's Respiratory Questionnaire between the treatment and control groups. A sum of six studies involving 1,928 participants were found to meet the inclusion criteria. The quality of evidence was high. The control group had significantly higher values for 6MWD, DLCO, and FVC compared to the ambrisentan treatment group. The rates of hospitalization and IPF worsening were considerably greater in comparison with the control group. The bosentan group exhibited significantly reduced rates of hospitalization and IPF worsening in comparison with the control group. Both drugs did not cause any raising in death or SAEs when in comparison with the control group. The findings of this research validate the effectiveness and safety of bosentan for treating IPF patients. This medication can enhance the quality of life for individuals with IPF without causing any significant increase in SAEs. However, it does not have a notable influence on the long-term prognosis. The findings of this research do not endorse the utilization of ambrisentan in individuals diagnosed with IPF.

Introduction: Pancreatic cancer is an aggressive tumor, and an estimated 57,600 new cases and 47,050 deaths were reported in 2020 in the US alone. Recent studies have targeted the tumor microenvironment (TME) for better delivery of systemic chemotherapy, like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles were identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR= 0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), but a statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group was observed. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there was an increased incidence of serious adverse events using PEGPH20 compared to standard therapies.

Safety of combination therapy with two bDMARDs in patients with rheumatoid arthritis: A systematic review and meta-analysis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itching and lesions that significantly impact patients' quality of life. Abrocitinib, a selective Janus kinase 1 (JAK1) inhibitor, has shown promise in treating AD by targeting inflammatory pathways linked to disease symptoms. This systematic review and meta-analysis evaluates the effectiveness of abrocitinib in reducing lesion severity and pruritus in AD patients. A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted on September 19, 2024, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were randomized controlled trials assessing abrocitinib's effects on lesion area and pruritus in AD patients. Data extraction and quality assessment were performed using the Cochrane risk of bias tool. Statistical analyses, including meta-regression and subgroup analysis, were conducted using Stata. Funnel plots were examined to assess publication bias. Five studies met inclusion criteria, with sample sizes ranging from 267 to 837 participants. Abrocitinib significantly improved Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI-75) scores, as well as pruritus scores on the Pruritus Patient Numeric Rating Scale (PP-NRS), compared to placebo (all P < 0.001). A dose-response effect was observed, with higher efficacy at the 200mg dose. The incidence of treatment-emergent adverse events (TEAEs) was higher in the intervention group, particularly at 200mg, though no significant difference was noted in serious adverse events (SAEs) between groups. Abrocitinib is effective in reducing lesion severity and pruritus in AD, with dose-dependent improvements. Despite a higher incidence of manageable TEAEs at 200mg, no significant increase in SAEs was observed, supporting abrocitinib's safety and efficacy as a treatment for moderate to severe AD. CRD420251056272.

BackgroundRadiation-induced xerostomia (RIX) is a frequent, debilitating complication of head and neck radiotherapy for cancer. Preclinical studies suggest that mesenchymal stem cells (MSCs) may protect and regenerate salivary glands, but clinical evidence remains fragmented. This study evaluates the safety and efficacy of MSC therapy for RIX patients.MethodsComprehensive searches of PubMed, Wiley Online Library, Cochrane, and CNKI were conducted up to July 2025 to identify relevant clinical studies. Two investigators independently screened records. A total of seven trials (n = 360 participants) were included. Meta-analyses were conducted using RevMan 5.4 and R Studio, with unstimulated whole salivary flow rate (UWS) as the primary endpoint. Secondary endpoints included stimulated whole salivary flow rate (SWS), Xerostomia Questionnaire (XQ) scores, and serious adverse events (SAE). Meta-analyses were conducted using RevMan 5.4 and R 4.5.1, with UWS as the primary endpoint. Heterogeneity was assessed by I2 and large-study effects by Egger’s test. The protocol was registered on PROSPERO (CRD420250521958).ResultsPooled analysis of the seven trials showed a statistically significant but clinically negligible increase in UWS with MSCs compared to controls (WMD = 0.02 mL/min, 95% CI: 0.00 to 0.03, p = 0.04). No significant differences were found for SWS (WMD = – 0.12 mL/min, 95% CI – 0.28 to 0.04) or XQ scores (WMD = – 0.54, 95% CI – 1.96 to 0.88; p = 0.46). The risk of SAE was not significantly different between groups (OR = 1.96, 95% CI 1.00-3.84, p = 0.05). Substantial heterogeneity was observed (I² >90%). Exploratory network meta-analysis suggested that bone marrow-derived MSCs (BMMSC) might outperform adipose-derived MSCs (ADMSC), but this finding is hypothesis-generating due to being based on a single BMMSC study.ConclusionsMSC transplantationresults in a statistically significant but clinically marginal improvement in UWS for RIX, with no significant increase in SAE. The current evidence does not support the superiority of MSC therapy over conventional management. Future large-scale trials are required to determine if optimized MSC strategies can achieve clinically meaningful benefits.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04824-2.

Background Colchicine is the most widely studied anti-inflammatory drug for patients with coronary artery disease (CAD), and has recently received a class IIa indication for administration in these patients by international guidelines. However, the recent CLEAR trial, the largest trial of colchicine in patients with acute coronary syndrome (ACS) to date, significantly challenged this recommendation. Among potential factors influencing the efficacy of colchicine, lower efficacy in ACS rather than chronic coronary syndrome (CCS), timing of administration and contemporary administration of other therapies have been claimed. Purpose To evaluate the benefits of colchicine in patients with CAD and the specific subgroups od CCS and ACS. Methods Randomized trials of colchicine in patients with CAD undergoing PCI were identified. Trial-defined major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction and stroke, and serious adverse events (SAE) were the primary efficacy and safety outcomes, respectively. Secondary outcomes included all-cause death and single components of the primary endpoints. Pairwise meta-analyses with interaction for the clinical presentation (i.e., ACS or CCS) and dosage (high- or low-dose) were conducted. Results A total of 19 studies including 21,425 patients were included. Of these, 7,435 (34.7%) were CCS patients. Compared with control, colchicine was associated with a significant reduction in MACE (IRR 0.71; 95% CI 0.58-0.88; Figure 1) without significant increase in SAE (IRR 0.95; 95% CI: 0.86-1.05). Colchicine also reduced rates of myocardial infarction (IRR 0.82; 95% CI 0.71-0.96) and any revascularization (IRR 0.74; 95% CI 0.55-0.99). Among other safety measures, colchicine administration was associated with significantly higher rates of gastrointestinal adverse events (IRR 1.68; 95% CI 1.23-2.28). No significant interaction between efficacy and clinical presentation was found (Figure 2), but a significant interaction for gastrointestinal adverse events and colchicine dose was detected (P=0.014), as the effects were primarily driven by high-dose colchicine (IRR 2.33; 95% CI 1.43-3.79). Conclusions In patients with CAD, colchicine administration reduces MACE, myocardial infarction and any revascularization independently of the clinical presentation. Colchicine was associated with a significant increase in non-serious gastrointestinal adverse events, which was more apparent in patients receiving higher dosages. In aggregate, these data suggest that low-dose colchicine may allow better net benefit profile across the whole spectrum of coronary artery disease.Figure 2.Interaction for presentation

Metformin monotherapy for adults with type 2 diabetes mellitus.