Real-world Safety Research Articles

Adverse events of nusinersen: a real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database

ABSTRACT Introduction Nusinersen, the initial FDA-approved medication, treats Spinal Muscular Atrophy. This study utilized the FDA’s adverse event reporting system (FAERS) database to examine, evaluate, and provide substantiation for the safety of Nusinersen to assist in clinical decision-making. Methods Nusinersen-related adverse reaction signals were mined using the reporting odds ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN), Multi-item Gamma-Poisson Shrinker (MGPS) models with Empirical Bayesian Geometric Mean (EBGM). The rate and frequency of reported adverse reactions were investigated. Results Nusinersen-induced adverse events were observed in 25 system organ categories (SOCs). A total of 230 disproportionate preferred terms (PTs) were eliminated using four algorithms. Cardiac arrest, autism spectrum disorder, and epilepsy emerged as potential new side effects not previously listed, warranting further attention for drug safety. Analysis of the age distribution of the signals found that younger patients should be watched out for upper respiratory tract infections and increased CSF pressure; senior patients should be extensively checked for symptoms of post-lumbar puncture syndrome and protein urine present. Conclusions Our investigation discovered potential signals of novel adverse drug events that could support clinical monitoring and risk identification of Nusinersen. However, these results should be interpreted with caution.

Real-world safety of dapagliflozin plus metformin in patients of type 2 diabetes mellitus in China: Post-hoc analysis of the DONATE study.

DONATE (NCT03156985) is a large-scale real-world study investigating the safety of dapagliflozin in Chinese type 2 diabetes mellitus (T2DM) patients. This post-hoc analysis aims to further evaluate the real-world safety of dapagliflozin plus metformin. Safety outcomes were assessed in patients receiving concomitant dapagliflozin and metformin, with or without other antidiabetics. The safety of dapagliflozin-based dual-therapies and dapagliflozin and metformin-based triple-therapies were also analysed. Among the 2,990 patients in DONATE, 2,165 (72.4 %) received concomitant metformin. Among these 2,165 patients, 780 (36.0 %) experienced ≥ 1 adverse event (AE), 129 (6.0 %) experienced serious AE (SAE), and 96 (4.4 %) experienced AE leading to dapagliflozin discontinuation. The most common AEs were upper respiratory tract infection (4.0 %), urinary tract infection (UTI, 2.1 %) and constipation (1.5 %). The most common AEs of special interest of dapagliflozin were UTI (2.3 %), genital tract infection (1.5 %) and hypoglycaemia (1.1 %). In the dapagliflozin and metformin dual-therapy subgroup, the incidences of AE, SAE and AE leading to dapagliflozin discontinuation were 26.7 %, 2.5 %, and 1.9 %, respectively, numerically lower than that of the total population and most other dual-therapy subgroups. These patients also had numerically improved metabolic outcomes than baseline. Dapagliflozin and metformin combination therapy is well-tolerated in real-world Chinese T2DM patients.

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)

ABSTRACT Objective Given the extensive use of atorvastatin in managing cardiovascular conditions and the surge in reported adverse drug reactions (ADRs), this study leverages the FAERS database to comprehensively evaluate atorvastatin-associated adverse events, thereby enhancing our understanding of its safety profile in real-world settings. Methods A retrospective observational pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q1 2024. Four algorithms – ROR, PRR, BCPNN, and EBGM – were employed to detect signals of adverse events (AEs) linked to atorvastatin through disproportionality analysis. Results Out of 17,627,340 reports in the FAERS database 81,955 involved atorvastatin. Consistently identified AEs across all four algorithms included musculoskeletal and connective tissue disorders, metabolic and nutritional disorders, and hepatobiliary disorders at the system organ class (SOC) level. A total of 4,575 significant disproportionate preferred terms (PTs) were observed across 23 SOCs, with key PTs being ‘immune-mediated myositis,’ ‘type 2 diabetes mellitus,’ ‘necrotizing myositis,’ ‘autoimmune myositis,’ and ‘myopathy.’ Additionally, unexpected AEs such as erectile dysfunction were identified. The median onset time for these AEs was 60 days, with most occurring within the first 30 days of treatment. Conclusion This study identified both expected and unexpected AEs associated with atorvastatin, highlighting the need for continued surveillance and providing valuable insights for clinicians to optimize atorvastatin use and address safety concerns.

ORPHEE: A Real-World Study on rIX-FP Prophylaxis Use in Adolescent/Adult Patients With Hemophilia B.

To assess the real-world efficacy and safety of recombinant factor IX albumin fusion protein (rIX-FP) in patients with hemophilia B (HB) in France. Data on dosing frequency, weekly consumption, and bleeds before-and-after switching to rIX-FP, were collected from December 2021 to February 2024. Annualized (spontaneous) bleeding rates [A(s)BRs] were calculated only in patients on prophylaxis with a follow-up ≥ 6 months. This interim analysis focused on 77 patients ≥ 12 years; 62 (81%) had severe HB. After switching to rIX-FP, the infusion interval was 14 (7-14) days. Weekly consumption was 43 (35.5-53) IU/kg. ABRs and AsBRs were 0.5 (0-1.9) and 0 (0-0.7) (n = 63) at 18.2 (12.3-21.9) months of follow-up. Prophylactic efficacy of rIX-FP was considered 'Excellent'/'Good' in 65/68 (95%) patients. Among the 43 patients previously treated with rFIXFc, 21 increased the infusion interval from 7 (7-11) days with rFIXFc to 14 (7-14) days with rIX-FP; 33/43 (77%) reduced weekly factor IX (FIX) consumption from 59.95 (46.35-77.93) to 42.5 (35.88-50.25) IU/kg. Patients maintained good protection against bleeds. This analysis confirmed that switching to rIX-FP allows for reducing injection frequency and FIX consumption while maintaining good bleed protection.

Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration

IntroductionDiabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be...

89. Real-world Safety and Efficacy of Teriflunomide (Tebazio®) in Iranian Females with Relapsing-Remitting Multiple Sclerosis

89. Real-world Safety and Efficacy of Teriflunomide (Tebazio®) in Iranian Females with Relapsing-Remitting Multiple Sclerosis

S19 Real-World Efficacy and Safety of Ozanimod in US Patients With Moderately to Severely Active Ulcerative Colitis: Initial Results from POLARIS, an Ongoing Phase 4 Open-Label Study

S19 Real-World Efficacy and Safety of Ozanimod in US Patients With Moderately to Severely Active Ulcerative Colitis: Initial Results from POLARIS, an Ongoing Phase 4 Open-Label Study

Efficacy and Safety of One Shot of Hyaluronic Acid in Hip Osteoarthritis: Postmarketing Clinical Follow-Up for Real-World Evidence.

This study aims to evaluate the real-world efficacy and safety of intra-articular (IA) hyaluronic acid (HA) injections in patients with hip osteoarthritis (OA). Given the increasing burden of hip osteoarthritis and limited evidence supporting viscosupplementation in this context, this research aims to provide valuable insights under real clinical practice conditions. An observational, cross-sectional and retrospective study was conducted in a cohort of patients with hip OA treated with a single injection of HA (Adant One, Meiji Pharma Spain, Spain) from January 2021 to December 2022. Data on patient demographics, clinical characteristics, and treatment outcomes were collected. Efficacy regarding pain relief and/or function improvement was assessed at 6 months using the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Data were pseudonymized. The study was approved by the Research Ethics Committee of the Autonomous Community of Aragon (CEICA). The study included 40 patients with a mean age of 62.8 years, with 72.5% being female. Significant improvement was observed six-months post-treatment: 25% and 18.5% reduction in pain (VAS and WOMAC, respectively), 11.6% improvement in function (WOMAC), 7.4% improvement in stiffness (WOMAC), and 13.6% improvement in total WOMAC. No adverse events were reported. A single injection of IA HA significantly improved pain and function in patients with hip OA. These findings support the use of viscosupplementation for hip OA management and underscore the need for further studies to confirm these results and assess the long-term benefits of IA HA in hip OA.

Real-World Safety Profile of Direct Oral Anticoagulants (DOACs): Disproportionality Analysis of Major Bleeding Events

BackgroundDirect Oral Anticoagulants (DOACs) have revolutionized the management of thrombotic conditions, providing more predictable and manageable anticoagulation compared to traditional vitamin K antagonists. Despite their success, major bleeding events remain a significant concern. This study aims to assess and compare the haemorrhagic risks associated with various DOACs using data from the FDA's Adverse Event Reporting System (FAERS). MethodsA retrospective disproportionality analysis of the FAERS database was conducted, covering the period from January 1, 2015, to December 31, 2023. The study focused on adverse bleeding events reported for DOACs. The Proportional Reporting Ratio (PRR) was calculated for each DOAC to identify disproportionate reporting of haemorrhagic events. Major haemorrhagic events were classified as those leading to hospitalization. The analysis also utilized the Medicare Part D dataset to estimate the usage of specific DOACs from 2015 to 2021. ResultsA total of 353,188 haemorrhagic events were identified, with 17,236 (4.9%) attributed to DOACs. The PRR for major haemorrhagic events was highest for Edoxaban at 14.1 (95% CI 13.93-14.85), followed by Dabigatran at 4.0 (95% CI 3.81-4.20), Apixaban at 3.53 (95% CI 3.47-3.61), and Rivaroxaban at 2.11 (95% CI 2.05-2.18). Edoxaban also had the highest PRR for cerebral haemorrhages. Medicare data indicated that Apixaban was the most commonly used DOAC (58.3%), followed by Rivaroxaban (34.5%). ConclusionsEdoxaban shows a significantly higher risk of major and cerebral haemorrhages compared to other DOACs, while Rivaroxaban demonstrates a lower overall risk of haemorrhage. These findings emphasize the need for careful consideration of bleeding risks in DOAC therapy. Continuous post-marketing surveillance is crucial for understanding the safety profiles of DOACs in real-world clinical settings, aiding clinicians and patients in making informed decisions about anticoagulant therapy.

Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis of Esketamine and Respiratory Depression.

Esketamine nasal spray (ESK) is approved, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults and for the treatment of depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. No adverse events (AEs) of respiratory depression were reported in ESK phase 3 clinical trials; however, postmarketing incidents of respiratory depression associated with ESK use have been observed. The Janssen Global Medical Safety (GMS) database was reviewed for cases meeting criteria for respiratory depression with ESK using 47 months of postapproval data, based on the Standardized Medical Dictionary for Regulatory Activities (MedDRA) preferred term (PT) acute central respiratory depression (broad). FAERS, EudraVigilance, and literature searches were performed to identify reports of respiratory depression related to ESK use. Fifty cases, representing 50 patients, in the GMS database met the case definition for respiratory depression; 8 of these had a stronger association with ESK use. The MedDRA PT hypopnea met the threshold for disproportionality with ESK in FAERS. The MedDRA PTs asphyxia, oxygen saturation decreased, respiratory depression, and apnea, met the threshold for disproportionality with ESK in EudraVigilance. Despite extensive soliciting of AEs for ESK with the US Risk Evaluation and Mitigation Strategy program, respiratory depression is infrequently observed with ESK treatment in the postmarketing setting (estimated incidence: 1 case per 20,000 treatment sessions). Symptoms are manageable and resolve with minor supportive measures. Monitoring for symptoms of respiratory depression, including pulse oximetry, is recommended within the postdose observation period.

Comparative Safety and Effectiveness of Bevacizumab Biosimilars to Originator for the Treatment of Metastatic Colorectal Cancer.

Ontario has publicly funded biosimilar bevacizumab for first-line metastatic colorectal cancer (mCRC) since 2019. Clinical trials demonstrate comparable efficacy and safety of bevacizumab biosimilars to originator bevacizumab. The objective of this study was to assess real-world safety and effectiveness of the implementation of bevacizumab biosimilars compared with originator bevacizumab in patients with mCRC. This was a population-based, retrospective study comparing Ontario patients starting treatment with bevacizumab biosimilars between August 12, 2019, and March 31, 2021, and starting treatment with originator bevacizumab between July 2, 2008, and August 11, 2019. Safety outcomes included death within 30 days of the last dose received, any hospitalization, direct hospitalization, and hospitalization resulting from bevacizumab-related toxicity, chemotherapy-related toxicity, and febrile neutropenia. Event rates were assessed using negative binomial and logistic regression. The effectiveness outcome was overall survival, calculated using Kaplan-Meier and Cox proportional hazards regression. A subgroup analysis compared safety and effectiveness outcomes between patients on bevacizumab biosimilar products and matched comparators. We identified 8,996 patients who initiated first-line treatment of bevacizumab for mCRC. Accounting for duration of follow-up, no significant differences were observed in the rate of hospitalization between treatment groups. No differences in overall survival (log-rank P>.05) or hazard ratios (propensity score-matched hazard ratio, 1.03; 95% CI, 0.92-1.16) were observed in the crude and propensity score-matched cohorts. Subgroup analysis demonstrated similar safety and effectiveness patterns. The demonstrated similarity in safety and effectiveness between bevacizumab biosimilars and originator bevacizumab provides further support for the use of and confidence in biosimilar products.

Real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia in Japan: the Orbit study.

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor that is approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan based on randomized clinical trial data. The aim of the real-world, retrospective Orbit study was to describe long-term clinical outcomes and management in adults (aged ≥ 20years) with CLL/SLL treated with ibrutinib, either as first-line (1L) treatment or for relapsed or refractory (RR) disease, in routine clinical practice in Japan between July 2018 and December 2020. A total of 246 patients were registered, and the safety and per-protocol sets included 237 and 234 patients, respectively. After a median follow-up of 35.7months, the 36-month progression-free survival rate was 80.9% in the 1L CLL cohort and 67.2% in the RR CLL cohort, and the 36-month overall survival rates were 90.8% and 83.7%, respectively. Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3 adverse events of special interest were atrial fibrillation (2.1%), infections (herpesvirus infection, fungal infection, or Pneumocystis jiroveci pneumonia; 1.7%), bleeding (3.8%), and second primary malignancy (2.5%). These findings confirm the long-term, real-world effectiveness and safety of ibrutinib for the treatment of Japanese patients with newly diagnosed or RR CLL/SLL.

Practical guide for disease-modifying medication management of children and adolescents with sickle cell disease.

Hydroxyurea has historically been the sole disease-modifying medication (DMM) for sickle cell disease (SCD). However, 3 newer DMMs, L-glutamine, voxelotor, and crizanlizumab, were approved for children and adolescents with SCD since 2017. Despite their emergence, treatment barriers, including access, affordability, and nonadherence, limit the optimization of DMMs in the clinical setting. Furthermore, there is limited work outlining real-world use and safety of the newer DMMs, and no published guidelines advise how best to select between DMMs or to use multiple in combination. Meanwhile, each DMM is associated with unique characteristics, such as tolerability, cost, and route of administration, which must be considered when weighing these options with patients and families. This article discusses DMMs for SCD and offers practical guidance on using the available DMMs in real-world settings based on published peer-reviewed studies and considering patient preferences. The recent withdrawal of one of these DMMs (voxelotor) from the market highlights the need for additional DMMs and evidence-based practices for adding DMMs and when to progress towards curative therapies.

Assessing real-world safety of plecanatide: a pharmacovigilance study based on the FDA adverse event reporting system.

Plecanatide is a selective gastrointestinal peptide used for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Given its widespread use, understanding the long-term safety of plecanatide in real-world settings is essential. Data for this study were sourced from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the first quarter of 2017 to the second quarter of 2024. Disproportionality analysis methods were employed to quantify adverse event signals associated with plecanatide. Additionally, a Weibull distribution analysis was conducted to assess changes in adverse events over time. Sensitivity analyses were performed to enhance the robustness of the findings. A total of 861 cases associated with plecanatide were identified, including 2057 adverse event reports. Common positive adverse events included diarrhea, constipation, abdominal distension, dissatisfaction with treatment, rectal tenesmus, increased fecal volume, abnormal gastrointestinal sounds, and gastrointestinal motility disorders. The majority of adverse events related to plecanatide occurred within the first 7days of treatment. Findings were consistent across sensitivity analyses. This study preliminarily explores the safety of plecanatide in real-world applications, revealing significant new adverse event signals. These findings provide important safety references for clinicians prescribing plecanatide for CIC and IBS-C.

Comparative Efficacy and Safety of Three Janus Kinase Inhibitors in Ulcerative Colitis: A Real-World Multicentre Study in Japan.

Three Janus kinase (JAK) inhibitors are approved for ulcerative colitis (UC) in Japan. To compare the real-world efficacy and safety of these three JAK inhibitors in UC. This was a multicentre, retrospective study of patients with UC started on JAK inhibitors. The primary outcome was clinical remission at 10, 26 and 58 weeks, and at the most recent follow-up. To compare the efficacy and safety among the JAK inhibitors, we created three matched cohorts (upadacitinib vs. filgotinib, tofacitinib vs. filgotinib and upadacitinib vs. tofacitinib) using propensity score matching. We identified 228 upadacitinib-treated patients (median follow-up 49 weeks; IQR 25-72), 215 filgotinib-treated patients (follow-up 56 weeks; IQR 17-82) and 159 tofacitinib-treated patients (follow-up 112 weeks; IQR 10-258). Clinical remission rates for upadacitinib, filgotinib and tofacitinib at the most recent follow-up were 72.8%, 50.6% and 45.8%, respectively. Over 70% of the patients previously treated with other biologics or JAK inhibitors achieved clinical remission with upadacitinib. On multivariate analysis, the number of previous advanced therapies was inversely associated with the efficacy of filgotinib and tofacitinib. Comparative analysis showed that upadacitinib-treated patients had higher efficacy and lower risk of discontinuation than patients treated with other JAK inhibitors. However, upadacitinib had a significant risk of acne. Considering the particularly high efficacy of upadacitinib, even in patients with refractory UC, filgotinib or tofacitinib may be considered as an upfront JAK inhibitor before using upadacitinib.

Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase4 and PROCLAIM Phase3 Studies with a Focus on Older Patients.

Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50years old, yet data on their response to disease-modifying therapies (DMTs) is limited. Dimethyl fumarate (DMF) is an oral DMT approved for treating relapsing MS. This analysis evaluated the safety, efficacy, and immunophenotype changes of DMF in patients ≥ 50years compared with patients < 50years. ESTEEM, a 5-year, real-world, observational phase4 study, assessed the safety and effectiveness of DMF, including treatment-emergent serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation. Absolute lymphocyte counts (ALCs) were recorded from a subset of patients. The PROCLAIM study, a phase3b interventional study, reported safety outcomes and lymphocyte subset changes in patients with relapsing-remitting MS (RRMS) treated with DMF. The study evaluated safety outcomes by analyzing the incidence of SAEs and detailed changes in CD4+ and CD8+ Tcell compartments over 96weeks of DMF treatment. ESTEEM included 4020 patients aged < 50years and 1069 aged ≥ 50years. AEs leading to discontinuation were reported by 19.6% patients < 50years and 29.6% of patients ≥ 50years, with gastrointestinal disorders being the most common. SAEs were reported by 5.2% of patients < 50years and 8.9% those ≥ 50years. In PROCLAIM, SAEs were reported in 13% of patients < 50years and 10% of those ≥ 50years. Median ALC decreased by 35% in patients < 50years and 50% in those ≥ 50years in ESTEEM, with similar patterns observed in PROCLAIM. ESTEEM found no unexpected safety signals in older patients and annualized relapse rates (ARRs) were significantly reduced in both age groups. Both studies indicated that DMF is efficacious and has a favorable safety profile in patients with RRMS aged ≥ 50years. ESTEEM (NCT02047097), PROCLAIM (NCT02525874).

Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study.

Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC. This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data. Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment. This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.

Real-world effectiveness and safety of fixed-ratio combination insulin glargine 100 u/ml plus lixisenatide in adults with type 2 diabetes (T2DM): subanalysis of the international, multicentre, prospective observational study SUCCESS in the Russian population

AIM: To evaluate the impact a fixed-ratio combination of insulin glargine(100U/ml) and lixisenatide(iGlarLixi) on the glycemic control in Russian study T2D population uncontrolled on OAD ± insulin therapy in real-world settings.MATERIALS AND METHODS: The Russian subanalysis of international, multicentre, prospective, observational SUCCESS study included 160 T2DM patients who had initiated iGlarLixi within 1 month prior to study inclusion from 11 regions of the Russian Federation. The primary endpoint — HbA1c change from baseline to month 6. Secondary endpoints: HbA1c change after 12 months, achievement of target HbA1c levels after 6 and 12 months; change in FPG and PPG, change in body weight after 6 and 12 months, iGlarLixi dose dynamics. Safety endpoints: adverse events, serious adverse events, adverse events of special interest, frequency of hypoglycemia during the study period.RESULTS: The average age of patients in the Russian population was 60.8±9.4 years; average duration of T2DM was 11.4 years, mean HbA1c — 9.3±1.5%; mean BMI 33.3 kg/m2. Prior to the study, most patients were on 2 (36.3%) and 3 OADs (27.5%), 32.5% — on insulin therapy. The mean change of HbA1c at month 6 was -1.81%, and -2.03% at month 12. 51.3% patients achieved individual HbA1c targets at month 12, 46.7% of patients achieved the HbA1c target without hypoglycemia and weight gain. The decrease of body weight in 12 months was -3.3±4.4 kg. During the study period, 17 cases of hypoglycemia were recorded (0.11 events per patient-year); 1 severe hypoglycemia (0.01 events per patient-year). The total number of adverse events (AEs) was 43(26.9%), serious AEs - 10 (6.3%).CONCLUSION: According to the results of this prospective real world sub-group analysis, initiation of iGlarLixi in Russian adults with T2DM uncontrolled on OADs ± insulin significantly improves glycemic control with low risk of hypoglycemia and no body weight increase.

Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM).

Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan-Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40-91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Prospective multicenter study of camrelizumab in real-world settings for asian patients with esophageal squamous cell carcinoma

BackgroundIn this study, we aimed to evaluate the real-world efficacy and safety of camrelizumab and identify clinicolaboratory factors that predict treatment outcomes in patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) receiving camrelizumab.MethodsHerein, 174 patients with unresectable advanced, recurrent, or metastatic ESCC treated with camrelizumab monotherapy (n = 30), camrelizumab + chemotherapy (CT; n = 91), and camrelizumab + radiotherapy (RT; n = 53) between October 1, 2019 and October 1, 2022 were included.ResultsThe median follow-up time was 20 months (range, 1–34 months). The median progression-free survival (PFS) and overall survival (OS) of the whole cohort were 8 months [95% confidence interval (CI), 6.5–9.5 months] and 14 months (95% CI, 11.2–16.8 months), respectively. After multivariate analysis, receiving > 4 cycles of camrelizumab was identified as an independent predictor of better PFS [hazard ratio (HR), 0.56; 95% CI, 0.38–0.827; P = 0.004] and OS (HR, 0.532; 95% CI, 0.341–0.83; P = 0.005). An intermediate-to-poor lung immune prognostic index (LIPI) was identified as an independent predictor of worse PFS (HR, 1.505; 95% CI, 1.032–2.196; P = 0.034) and OS (HR, 1.657; 95% CI, 1.094–2.51; P = 0.017). The disease control rate of patients in the camrelizumab monotherapy group, camrelizumab + CT group, and camrelizumab + RT group was 92.3% (95% CI, 74.9–99.1%), 90.6% (95% CI, 82.3–95.9%), and 96.1% (95% CI, 86.8–99.5%), respectively. The treatment-related adverse events (AEs) of grade 3 or higher were reported in 67 patients (38.5%). The most common treatment-related AEs were decreased neutrophil count (23.0%), decreased white blood cell count (19.5%), anemia (7.5%), and pneumonitis (4.6%). One patient (0.6%) died from a treatment-related AE of immune checkpoint inhibitor-induced myocarditis.ConclusionCamrelizumab was safe and effective as both monotherapy and part of a combination therapy. Longer PFS and OS were associated with receiving > 4 cycles of camrelizumab and having a good LIPI. LIPI can be used as a prognostic biomarker for ESCC patients receiving camrelizumab + RT.Trial registrationClinicalTrial.gov Identifier: CHICTR2000039499. Registered: 19th October 2020.