OBJECTIVE:We aimed to evaluate the rationality of proton pump inhibitor (PPI) prescription in elderly outpatients aged ≥ 65 years, characterize inappropriate prescription patterns, and identify the factors associated with label-discordant prescription. MATERIALS AND METHODS:A retrospective single-center study was conducted at Beijing Tongren Hospital. Data were extracted for outpatients aged ≥ 65 years who received PPIs between November 2024 and October 2025. Only the first visit of each patient was included (n = 3,038) to avoid non-independence. Prescription rationality was assessed using the Clinical Application Guidelines for Proton Pump Inhibitors (2020 Edition) and package inserts. Two binary outcomes were defined: any label-discordant prescription (composite of inappropriate indication, dose, drug interaction, or label-discordant frequency) and pure excessive frequency (twice-daily dosing without other discordance). Logistic regression analysis was conducted to identify the associated factors. RESULTS:Among 3,038 first-visit patients, 281 (9.25%) had label-discordant prescriptions (rational use rate: 90.75%). Excessive frequency (twice-daily dosing) was the most common type of label-discordant prescription (206 patients, 73.31% of discordant cases), of whom 204 exhibited no other discordance (pure excessive frequency). Inappropriate drug interactions were observed in 34 patients (12.10%), inappropriate indications were detected in 19 (6.76%) patients, and inappropriate single-dose was found in 13 (4.63%) patients. Multivariable analysis showed that male sex (OR = 0.681), having ≥ 5 diagnoses (OR = 0.721), and non-gastroenterology department (OR = 0.235) were associated with lower odds of label-discordant prescription, while senior physician title (OR = 1.628) was associated with higher odds of label-discordant prescription. Age ≥ 75 years did not show a significant association (p = 0.981). Results for pure excessive frequency were directionally consistent. CONCLUSION:In this sample of elderly outpatients, the label-discordant prescription rate of PPI was 9.25%, with excessive frequency representing the predominant type. Male sex, a higher number of diagnoses, and non-gastroenterology departments were associated with lower odds, whereas a senior physician title was associated with higher odds. Given the exclusion of prophylactic use and single-center design, these findings should not be generalized to all PPI prescription practices. Future studies should include prophylactic prescriptions and disease severity measures.
OBJECTIVES:To report the occurrence of elevations (spikes) in interstitial fluid glucose concentrations (IFGC) following magnesium citrate administration during preparation for colonoscopy in a patient with type 1 diabetes mellitus (T1DM). To ascertain, using a comprehensive analysis of large claims databases, the proportion of diabetes mellitus (DM) patients who are vulnerable to showing elevated blood glucose levels following magnesium citrate administration. CASE PRESENTATION:A female patient aged 35 years received pretreatment with 100 g of magnesium citrate in 1.8 L of water 2 hours before a colonoscopy. After an interval of 41 minutes, the patient self-administered insulin to correct an IFGC increase from 108 to 176 mg/dL. However, the IFGC reached a peak of 251 mg/dL, resulting in marked thirst, frequent urination, and palpitations. Based on a database cohort of ~ 3 million patients, there were 105,348 patients with a risk for elevations in the blood glucose level after receiving magnesium citrate, of whom 9.5% (n = 9,957) had DM and 96 had T1DM. CONCLUSION:Analysis of a colonoscopy patient with T1DM and magnesium citrate-induced elevations in IFGC, and evaluation of patients in a large database with a similar risk, emphasizes the need for caution when administering such agents and in particular in patients with T1DM. We suggest that alternative preparations for colonoscopy in diabetic patients may be warranted.
OBJECTIVE:To investigate the impact of the 2021 guideline update on guideline-directed medical therapy (GDMT) utilization in patients with heart failure (HF). BACKGROUND:The 2021 update of the Japanese guidelines for HF management followed the introduction of sacubitril/valsartan and dapagliflozin into clinical practice. However, the impact of this guideline update on drug utilization patterns remains unclear. MATERIALS AND METHODS:Patient data were obtained from the Japanese employee health insurance claims database (JMDC). The simple GDMT score was determined based on the combination and dose of four key pharmacological classes: β-blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Because a simple GDMT score of ≥ 5 has been associated with improved prognosis in patients with HF, patients with scores ≥ 5 were classified into the high-score group for analysis. RESULTS:Following the guideline update, the proportion of patients in the high-score group increased from 6.97% (n = 4,013) to 9.33% (n = 6,363), standardized difference 0.09. The mean simple GDMT score also showed a small but statistically significant increase (5.72 ± 0.79 vs. 6.00 ± 1.09) with standardized difference 0.28. This upward trend was particularly marked for the prescription rates of sacubitril/valsartan and dapagliflozin (sacubitril/valsartan: 1.40% before the update vs. 22.57% after the update; standardized difference, 0.69; dapagliflozin: 12.41% before the update vs. 26.64% after the update; standardized difference, 0.36). CONCLUSION:The 2021 guideline update was associated with increased use of sacubitril/valsartan and dapagliflozin, resulting in greater overall GDMT intensity. However, these findings are limited to data from 2021, and further long-term studies are needed to evaluate trends in GDMT utilization.
OBJECTIVES:i) To improve the accuracy of initial dosing design in vancomycin therapeutic drug monitoring (TDM) using a free web application of practical antimicrobial TDM (PAT) for vancomycin, ii) to identify patient subgroups in emergency and critical care settings with overestimated predicted population mean serum vancomycin concentrations (PRED), and iii) to calculate appropriate PRED scaling factors. MATERIALS AND METHODS:Vancomycin serum concentrations in patients treated at the Emergency and Critical Care Centers of the University of Miyazaki Hospital, Japan, were simulated using a population pharmacokinetic model. Patients were classified based on the ratio of observed-to-predicted serum vancomycin concentrations (OBS/PRED). Those with a ratio < 0.67 were assigned to the low-trough group, while those with values ≥ 0.67 were the control group. Changes in patient data in the period from admission to immediately before vancomycin administration were analyzed, and scaling factors minimizing the mean squared error (MSE) between PRED and OBS were determined for subgroups more common in the lowtrough group. MSE and root mean squared error (RMSE) values before and after PRED scaling were compared. RESULTS:A total of 47 patients were analyzed, of which 23 were assigned to the low-trough group and 24 to the control group. The low-trough group showed a significantly higher prevalence of patients with creatinine clearance (CCR) < 15 mL/min, albumin < -0.5 g/dL, and trauma. For these subgroups, PRED scaling factors ranged from 0.53 to 0.64. The optimal scaling factor was 0.53 for ΔCCR > 15 mL/min, reducing the RMSE from 5.1 to 4.0 (μg/mL). CONCLUSION:PRED scaling factors were derived to potentially improve the accuracy of initial vancomycin dosing using PAT, and ΔCCR > 15 mL/min, ΔALB < -0.5 g/dL, and trauma were identified as key factors.
OBJECTIVE:To assess the clinical efficacy of a modified Lize Tongqi decoction in combination with acupuncture, moxibustion, and local stimulation of the Xinwu acupoint in the treatment of pediatric snoring. MATERIALS AND METHODS:A randomized controlled trial was conducted in a cohort of 60 pediatric patients (mean age of 7.9 years) diagnosed with snoring. Patients were assigned to either a study group (n = 30) or a control group (n = 30). The study group was treated using modified Lize Tongqi decoction, acupuncture, moxibustion, and stimulation of the Xinwu acupoint (twice weekly for 8 weeks) whereas the control group was treated with conventional Western medicine (oral montelukast once nightly and mometasone furoate nasal spray once nightly for 8 weeks). The severity of symptoms including nasal congestion, nocturnal snoring, and breathing through the mouth was assessed prior to, and following the treatment intervention. Changes in the Obstructive Sleep Apnea-18 (OSA-18) quality of life score and the adenoid-to-nasopharyngeal (A/N) ratio were measured and compared between groups. RESULTS:Post-treatment comparisons showed significantly greater improvements in nasal congestion, snoring, and breathing through the mouth in the study group, and the reductions in both OSA-18 scores and A/N ratios were significantly greater. (Between-group differences p < 0.05). No adverse events were observed in either group. CONCLUSION:The combination of modified Lize Tongqi decoction with acupuncture, moxibustion, and Xinwu acupoint stimulation effectively reduced symptoms of airway obstruction and improved quality of life in pediatric patients with snoring. The combination therapy is a new, non-surgical therapeutic option for the clinical management of this potentially serious disorder.
OBJECTIVE:To describe the treatment patterns and reoperation rates after claims-defined postoperative periprosthetic joint infection (PJI) identified 1 - 6 months after total knee or hip arthroplasty using a Japanese nationwide claims database. MATERIALS AND METHODS:Patients who underwent total knee or hip arthroplasty between 2005 and 2017 were identified. Claims-defined postoperative PJI was operationally defined as infection-related claims accompanied by systemic antibacterial treatment in 1 - 6 months after arthroplasty. The agents targeting methicillin-resistant Staphylococcus aureus (MRSA) included vancomycin, daptomycin, linezolid, and teicoplanin. The primary outcome was reoperation after claims-defined postoperative PJI. RESULTS:Among the 2,805 patients, 59 (2.1%) developed postoperative PJI 1 - 6 months after arthroplasty. Of these, 8 underwent immediate surgical intervention, and the remaining 51 patients were initially managed with antibiotic treatment without surgical intervention. Of these, 12 received anti-MRSA agents and 39 received non-MRSA agents. Reoperation was performed in 3 of 12 (25.0%) patients who received anti-MRSA agents and 6 of 39 (15.4%) patients who did not receive anti-MRSA agents. Among the patients treated with anti-MRSA agents, 11 of 12 (91.7%) required second- or third-line therapy. Diabetes mellitus was present in 66.7% and 83.3% of the reoperated patients who received and did not receive anti-MRSA agents, respectively; liver disease was observed in 66.7% and 16.7% of the patients, respectively. CONCLUSION:This claims-based descriptive analysis indicated that treatment escalation and reoperation were observed after claims-defined postoperative PJI identified 1 - 6 months after arthroplasty. Because pathogen data were unavailable and receipt of anti-MRSA agents was used as a treatment-based classification, these findings should be interpreted as descriptive treatment-pattern data rather than microbiologically confirmed comparisons.
BACKGROUND:Anamorelin is the first drug approved for treating cancer-associated cachexia in Japan. However, factors influencing its discontinuation beyond a 12-week period have not been well studied. Moreover, death occurs in patients with cancer-associated cachexia and may compete with treatment discontinuation. OBJECTIVE:To investigate predictors of anamorelin discontinuation during a 48-week observation period, accounting for competing mortality risk. MATERIALS AND METHODS:This retrospective observational study investigated patients who commenced anamorelin administration for cancer-associated cachexia between October 1, 2021, and December 31, 2023, at Kindai University Nara Hospital. Predictors of discontinuation were evaluated using a multivariate Cox proportional hazards model to estimate HRs and 95% CIs. The Fine-Gray subdistribution hazards model was additionally applied, treating death as a competing event. A total of 93 patients were evaluated. RESULTS:An Eastern Cooperative Oncology Group performance status (PS) of ≥ 2 (adjusted HR 2.25, 95% CI 1.33 - 3.80, p = 0.003) and a prognostic nutritional index (PNI) of ≤ 39.6 (adjusted HR 1.79, 95% CI 1.10 - 2.90, p = 0.019) were predictors of discontinuation. Conversely, the Fine-Gray subdistribution hazards model identified PS ≥ 2 as significant (adjusted SHR 1.95, 95% CI 1.17 - 3.24, p = 0.010). CONCLUSION:In patients with cancer-associated cachexia, baseline PS and PNI were associated with anamorelin discontinuation. Furthermore, competing risk analysis demonstrated PS was the primary determinant of anamorelin discontinuation, whereas PNI may be more closely associated with mortality risk. Therefore, early diagnosis of cancer-associated cachexia and timely initiation of anamorelin before declines in PS and PNI may enable long-term administration.
OBJECTIVE:To characterize intra-patient variability in belumosudil exposure during coadministration of two azole antifungals that differ in cytochrome P450 3A4 (CYP3A4) inhibition strength - voriconazole (strong) vs. isavuconazole (moderate) - in a patient with steroid-refractory chronic graft-versus-host disease (cGVHD), and to discuss the subsequent implications for therapeutic drug monitoring (TDM). CASE HISTORY:A man in his 50s with pulmonary cGVHD was initiated on belumosudil 200 mg once daily after cord blood transplantation, which was later increased to 200 mg twice daily (400 mg/day). Concomitant voriconazole was switched to isavuconazole due to elevated galactomannan levels and Common terminology criteria for adverse events (CTCAE) grade 2 hepatotoxicity. A single plasma sample was collected at 2 hours post-dose (C2) to approximate the peak exposure, based on a reported median time to maximum concentration of ~ 2 hours in healthy Japanese adults. RESULTS:Over the clinical course, 28 C2 samples were analyzed (18 with voriconazole and 10 with isavuconazole). The overall median C2 was 857.04 ng/mL (range, 173.59 - 2,749.19). The median C2 was significantly higher with voriconazole (889.88 ng/mL) than with isavuconazole (395.96 ng/mL) according to the exact Wilcoxon signed-rank test (p < 0.001). Median plasma concentrations of coadministered azoles were 1.94 µg/mL (voriconazole) and 7.04 µg/mL (isavuconazole). CONCLUSION:Belumosudil exposure varied according to the degree of CYP3A4 inhibition (voriconazole > isavuconazole). These intra-patient data, together with clinical factors affecting absorption and hepatic function, support consideration of TDM and careful antifungal selection when combining belumosudil with azoles, particularly in pulmonary cGVHD where treatment responses are often limited.
OBJECTIVE:To retrospectively analyze the clinical safety and adverse drug reactions (ADRs) of sintilimab, to evaluate risk factors for ADR occurrence, and to develop a predictive model to support individualized treatment strategies. MATERIALS AND METHODS:Medical records of patients who received sintilimab treatment in the period January 2021 to December 2022 were examined. Clinical data, including demographic characteristics, medication details, and ADRs were recorded and evaluated using univariate and multivariate logistic regression analyses to identify independent risk factors for sintilimab-induced ADRs. Variables such as gender, age, comorbidities, and treatment regimens were included. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive accuracy of individual and combined risk factors, enabling the safety profile of sintilimab to be established. RESULTS:A total of 337 cases were retrieved of which 208 (61.72%) referred to patients who experienced ADRs. Multivariate analysis identified combination drug therapy (OR = 25.670, 95% CI: 11.319 - 58.218, p < 0.001) and pretreatment baseline assessment (OR = 0.388, 95% CI: 0.191 - 0.789, p = 0.009) as two independent risk factors. The logistic model indicated that the combined prediction ability of these factors gave an area under the curve (AUC) of 0.800 (p < 0.001), which indicated prediction superiority compared to using the factors alone. Cross-validation using 115 cases demonstrated an accuracy of ~ 80.87% for the model. CONCLUSION:Combination therapy and pretreatment baseline assessment are independent risk factors for ADRs occurring during therapy with sintilimab. The combined predictive model derived shows high accuracy and may have value in predicting treatment risks and managing personalized medication.
Compound glycyrrhizin tablets, derived from licorice root, are widely used for their anti-inflammatory and hepatoprotective properties. However, their active metabolite, glycyrrhetinic acid, can induce acquired apparent mineralocorticoid excess (AME) - a clinical syndrome where cortisol abnormally activates mineralocorticoid receptors due to the inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), mimicking primary aldosteronism. We report a case of a 57-year-old male who developed severe hypertension and hypokalemia after 30 days of treatment with compound glycyrrhizin (150 mg, t.i.d.). Laboratory investigations revealed profound hypokalemia (2.03 mmol/L) and metabolic alkalosis. Critically, both plasma renin activity (< 0.5 μIU/mL) and aldosterone levels (2.4 - 2.7 ng/dL) were significantly suppressed, effectively ruling out primary and secondary hyperaldosteronism. A diagnosis of acquired AME was established based on the temporal relationship with glycyrrhizin intake, the "double-low" hormonal profile, and the exclusion of Cushing's syndrome. Following treatment with amlodipine and potassium supplementation, the patient's symptoms resolved. At the 2-week post-discharge follow-up, after discontinuing all medications, his blood pressure remained stable (< 140/90 mmHg) and serum potassium normalized to 4.55 mmol/L, confirming the reversible nature of acquired AME.
OBJECTIVE:Cancer cachexia is associated with poor tolerance to anticancer therapies and reduced survival rates. Anamorelin, a ghrelin receptor agonist, has been introduced for the management of cachexia; however, early discontinuation and variable therapeutic responses are frequently observed in clinical practice. We aimed to identify the real-world predictors of early discontinuation and therapeutic response to anamorelin. MATERIALS AND METHODS:We conducted a retrospective cohort study of 90 patients with cancer cachexia who received anamorelin therapy. Early discontinuation was defined as the cessation of treatment within 3 weeks. Therapeutic response was evaluated using changes in the modified Glasgow Prognostic Score (mGPS) in patients who continued treatment and had evaluable laboratory data. Nutritional and inflammatory indices, including the prognostic nutritional index (PNI), were assessed. Multivariate logistic regression analyses were performed to identify independent predictors. RESULTS:43 (47.8%) patients discontinued anamorelin treatment within 3 weeks. Multivariate analysis showed that high baseline white blood cell count, low baseline PNI, and gastrointestinal tumor type were independently associated with early discontinuation. Among 38 evaluable patients in the continuation group, 14 (36.8%) demonstrated improvement or stabilization of the mGPS. A high baseline PNI and the absence of concomitant nonsteroidal anti-inflammatory drug use were independently associated with a therapeutic response. CONCLUSION:Baseline nutritional and inflammatory statuses strongly influence both treatment continuation and response to anamorelin. The PNI is a practical predictor for identifying patients who are likely to benefit from therapy. Early intervention before severe nutritional deterioration may optimize the outcomes of patients with cancer cachexia.
OBJECTIVES:To investigate differences in drug-induced dysphagia profiles among causative drugs, with a focus on reporting risk, patient age, and time to onset. BACKGROUND:Drug-induced dysphagia is one of several causes of dysphagia. However, its detailed profile, including differences among drugs and age groups, has not yet been thoroughly examined. MATERIALS AND METHODS:Data were obtained from the Japanese Adverse Drug Event Report Database. Reports submitted between April 2004 and October 2021 were analyzed. The 10 drugs with the highest number of reports of drug-induced dysphagia were selected as the target drugs. Reporting odds ratios were calculated to evaluate the association between each drug and dysphagia. The primary endpoint was the reporting odds ratio, while age distribution and time to onset were secondary outcomes. RESULTS:A total of 756,965 reports were analyzed. All target drugs were associated with drug-induced dysphagia. Cevimeline was identified as a novel finding because dysphagia was not observed during clinical trials. For most drugs, dysphagia occurred within approximately 25 days of administration. In contrast, paroxetine and milnacipran were associated with dysphagia even after long-term use. The age distribution of reported cases differed by drug, suggesting drug-specific differences in susceptible age groups. CONCLUSION:Drug-induced dysphagia profiles differ among drugs, particularly in terms of timing of onset and patient age distribution. Therefore, clinicians should consider both the causative drug and the patient's age when monitoring for dysphagia.
OBJECTIVES:To assess the use of laboratory monitoring, folic acid supplementation, and folinate calcium therapy in patients with rheumatoid arthritis (RA) receiving first-line methotrexate (MTX) according to the 2019 Japan College of Rheumatology safety updates and using a large Japanese claims database (DeSC). MATERIALS AND METHODS:Patient data for the period 2015 - 2020 were retrieved from the database, and patients were identified who had presented with active disease. The number of patients commencing with MTX treatment and receiving concomitant disease-modifying antirheumatic drug and folic acid supplementation were determined together with information on recommended laboratory testing (blood tests, serum creatinine, chest radiography, and KL-6) in the year prior to MTX initiation. The impact of the 2019 Japan College of Rheumatology guidelines was assessed by comparing the extent of folic acid supplementation before and after publication of the guidelines. RESULTS:Of the 1,574 patients identified with active RA, 919 (58.4%) started MTX. Folic acid was co-administered in 85.1% of MTX users, with no significant change in supplementation rates before and after the introduction of the 2019 guidelines (81.8 vs. 82.2%, p = 0.56), indicating that these safety protocols were already well-established. Baseline blood tests were carried out in 99.8% and chest radiography in 69.2% of patients. After commencing MTX treatment, the monitoring of serum creatinine (87.2 vs. 93.7%, p < 0.05) and KL-6 (15.2 vs. 28.4%, p < 0.05) increased significantly. The frequency of chest radiography decreased to 56.0% (p < 0.05), reflecting a shift toward more sensitive diagnostic tools in clinical practice. No patients required folinate calcium rescue therapy. CONCLUSION:MTX prescribing and monitoring in RA is generally carried out in accordance with clinical guidelines. Although folic acid supplementation is recommended and widely implemented, ~ 20% of patients do not receive it. Monitoring is generally carried out rigorously, but safety data indicate that these measures should receive more attention in high-risk elderly populations who were probably under-represented in this study.
Antidepressant overdose is a prevalent method of self-harm in patients with depression including bipolar disorder. According to the published literature, typical adverse effects are seizures, prolonged QT intervals, and arrhythmias, with cardiotoxicity primarily observed in adults. This paper reports the first documented case of an 11-year-old adolescent with depression who ingested a massive overdose comprising sertraline (60 tablets at 50 mg, giving a total dose of 3 g), quetiapine fumarate (50 tablets at 100 mg giving a total dose of 5 g) and lamotrigine (120 tablets at 25 mg giving a total dose of 3 g). At ~ 4 hours post ingestion, the patient developed hypoxemia, hypotension, persistent seizures, resulting in cardiac arrest. This case report offers critical insights into the clinical management of such cases involving pediatric populations.
OBJECTIVE:To investigate safety signals associated with recombinant human growth hormone (rhGH) using the FDA Adverse Event Reporting System (FAERS) and make recommendations for its application. BACKGROUND:rhGH is widely used in the management of pediatric growth disorders, but a comprehensive evaluation of its safety in pediatric populations is limited. MATERIALS AND METHODS:Adverse event (AE) reports involving patients under 18 years of age where rhGH was the primary suspect (PS) drug were retrieved from the FAERS database for the period beginning the first quarter of 2004 to the end of the third quarter of 2024. The reports were standardized and duplicate reports removed. Disproportionality analysis of AE signals was conducted using four complementary methods, namely i) reporting odds ratio (ROR), ii) proportional reporting ratio (PRR), iii) Bayesian confidence propagation neural network (BCPNN), and iv) empirical Bayesian geometric mean (EBGM). RESULTS:A total of 33,888 AE reports were retrieved and analyzed. Disproportionality analysis identified 167 positive signals across 19 System Organ Classes (SOCs), the most frequently of which was "Investigations," and the most common preferred term (PT) was "Arthralgia". In addition to confirmed AEs, several endocrine-related signals were also recognized including a) fluctuations in thyroid-stimulating hormone, b) increase in unbound concentrations of thyroxine, c) type 1 diabetes mellitus, d) low concentrations of high-density lipoprotein, and e) abnormal body odor. CONCLUSION:A comprehensive safety profile was established for rhGH when used in pediatric populations and comprising several newly identified potential AE signals. The findings underscore the importance of surveillance to mitigate risks and ensure the safe clinical use of rhGH.
Apremilast is a pioneering oral selective phosphodiesterase-4 inhibitor for the treatment of psoriasis. To evaluate and compare the pharmacokinetic properties and bioavailability of apremilast tablets manufactured by Nanjing Haijing Pharmaceutical Company (Nanjing, China) with apremilast tablets certified by Celgene Europe B.V. (Utrecht, The Netherlands), we conducted a randomized, open-label, single-dose, two-period, crossover study in healthy Chinese subjects under fasted and fed conditions. Eligible subjects were randomly assigned to receive reference or test apremilast tablets in the first treatment period and the other formulation in the second period. Serial blood samples were collected for pharmacokinetic analysis. Adverse events were recorded. A total of 28 healthy subjects were enrolled in the fasting cohort and 36 subjects in the fed cohort. The 90% confidence intervals of the geometric mean ratios of the test to reference formulations were 91.56 - 106.18% for Cmax, 96.08 - 108.18% for AUC0-t, and 96.02 - 107.67% for AUC0-∞ in the fasting cohort, and 95.15 - 107.05% for Cmax, 105.13 - 113.45% for AUC0-t, and 104.80 - 111.91% for AUC0-∞ in the fed cohort, all of which were within the bioequivalence range of 80.00 - 125.00%. There were no serious adverse events. The results showed that the test and reference apremilast tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.
OBJECTIVE:To evaluate the effectiveness, safety, and tolerability of Yimmug, a novel, highly purified, 10% human plasma-based intravenous immunoglobulin (IVIG) preparation, in patients with secondary immunodeficiency (SID) under real-world conditions. MATERIALS AND METHODS:This interim analysis is based on data from a multicenter, prospective, non-interventional study conducted with out-patients in Germany. Effectiveness was assessed by changes in (i) serum IgG levels, (ii) severe infection rates, (iii) clinical symptoms, and (iv) patient-reported quality of life (QoL) at three treatment intervals (after 3, 12, and 24 IVIG infusions) compared to baseline. Safety was evaluated through documentation of adverse events (AEs), including adverse drug reactions (ADRs), while tolerability was assessed by investigators. RESULTS:A total of 119 SID patients received 726 IVIG infusions at a median (IQR) dose of 0.3 (0.2 - 0.3) g/kg over a median (IQR) duration of 1.4 (0.4 - 2.9) years, with a median interval of 30.1 days between infusions. Serum IgG trough levels increased, with the proportion of patients achieving IgG ≥ 6 g/L rising from 30.3% at baseline to 66.7% after both 12 and 24 infusions. The mean annual rate of infections requiring antibiotics decreased from 2.3 at baseline to 0.0 after 3 and 12, and to 0.4 after 24 infusions, respectively. The new IVIG was well tolerated, and patients' clinical symptoms and QoL improved during treatment. AEs were reported in 20 (16.8%) patients, with 41 events in total, while ADRs occurred in 9 (7.6%) patients, with 16 events. Serious AEs (SAEs) occurred in 4 (3.4%) patients, involving 5 events, but no serious ADRs (SADRs) were reported. CONCLUSION:This interim analysis shows that the risks are minor compared to the benefits of this novel IVIG preparation in the management of SID.
