Cancers (Basel). 2023 Oct 9;15(19):4904. doi: 10.3390/cancers15194904.

ABSTRACT

BACKGROUND: Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC). Unlike hormone-based treatments for mCRPC, PARPis are not without drug-related hematological adverse events.

OBJECTIVE: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer.

STUDY METHODOLOGY: A systematic review and meta-analysis using the PRISMA guidelines was performed for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. PubMed, Embase, and Ovid All EBM reviews-Cochrane were queried from inception to 9 June 2023. The Mantel-Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities.

RESULTS: The systematic review retrieved eight phase II and III RCTs; specifically, eight were included in the anemia, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes. Compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of all-grade anemia (RR, 3.37; 95% CI, 2.37-4.79; p < 0.00001), thrombocytopenia (RR, 4.54; 95% CI, 1.97-10.44; p = 0.0004), and neutropenia (RR, 3.11; 95% CI, 1.60-6.03; p = 0.0008). High-grade anemia (RR, 6.94; 95% CI, 4.06-11.86; p < 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80-10.88; p < 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77-17.23; p = 0.10) showed no significant association. Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities.

CONCLUSION: PARPis were associated with an increased risk of hematological AEs. Future studies with more pooled RCTs will enhance this understanding and continue to inform patient-physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.

PMID:37835597 | DOI:10.3390/cancers15194904

Medicine (Baltimore). 2023 Oct 13;102(41):e35327. doi: 10.1097/MD.0000000000035327.

ABSTRACT

BACKGROUND AND PURPOSE: Treating vitiligo in clinical practice is challenging. Furthermore, oral drugs used in Western medicine have considerable side effects and are unsuitable for long-term treatment. In contrast, Chinese patent medicines (CPMs) are more suitable for long-term oral vitiligo treatment, but medical evidence of their efficacy and safety is lacking. Therefore, in this study, the efficacy and safety of CPMs were evaluated and ranked using a Bayesian network meta-analysis.

METHODS: Seven Chinese and English databases were searched for all relevant articles published up to February 2023. The Bayesian network meta-analysis method was used to analyze the extracted data to evaluate efficacy and safety.

RESULTS: Six common CPMs for treating vitiligo were selected in our study, and 48 targeted articles and 4446 patients were included. This study showed that Qubai Babuqi tablets (QT) were the most effective for short-term treatment of vitiligo, and that vitiligo capsules or pills (VCP) were the most effective for long-term treatment, together with compound Quchong Banjiuju pills (QP). In terms of surface area under the cumulative ranking curve (SUCRA) values, the order of efficacy of each treatment was as follows: QT (92.18%) > Taohong Qingxue pills (TP) (63.81%) > VCP (55.53%) > QP (50.72%) > Bailing tablets or capsules (BTC) (49.01%) > Baishi pills (BP) (35.69%)>routine therapy (RT) (3.1%) in terms of total effective rate and QT (92.05%) > VCP (71.50%) > QP (66.60%) > TP (42.95%) > BTC (39.66%) > BP (36.60%)>RT (0.6%) in terms of improvement rate. In addition, the safety of the 6 CPMs did not significantly differ in terms of adverse effects. The SUCRA values indicated that QT performed slightly worse than other drugs.

DISCUSSION: In treating vitiligo, QT is most effective but only suitable for short-term administration owing to its poor safety. VCP and QP could be used as first-choice long-term medications. TP may positively affect repigmentation in patients with limited lesion areas.

PMID:37832097 | PMC:PMC10578774 | DOI:10.1097/MD.0000000000035327

Drug Ther Bull. 2023 Oct 13:dtb-2023-000054. doi: 10.1136/dtb.2023.000054. Online ahead of print.

NO ABSTRACT

PMID:37833039 | DOI:10.1136/dtb.2023.000054

Nucleic Acids Res. 2023 Oct 13:gkad832. doi: 10.1093/nar/gkad832. Online ahead of print.

ABSTRACT

Leveraging genetics insights to promote drug repurposing has become a promising and active strategy in pharmacology. Indeed, among the 50 drugs approved by FDA in 2021, two-thirds have genetically supported evidence. In this regard, the increasing amount of widely available genome-wide association studies (GWAS) datasets have provided substantial opportunities for drug repurposing based on genetics discoveries. Here, we developed PharmGWAS, a comprehensive knowledgebase designed to identify candidate drugs through the integration of GWAS data. PharmGWAS focuses on novel connections between diseases and small-molecule compounds derived using a reverse relationship between the genetically-regulated expression signature and the drug-induced signature. Specifically, we collected and processed 1929 GWAS datasets across a diverse spectrum of diseases and 724 485 perturbation signatures pertaining to a substantial 33609 molecular compounds. To obtain reliable and robust predictions for the reverse connections, we implemented six distinct connectivity methods. In the current version, PharmGWAS deposits a total of 740 227 genetically-informed disease-drug pairs derived from drug-perturbation signatures, presenting a valuable and comprehensive catalog. Further equipped with its user-friendly web design, PharmGWAS is expected to greatly aid the discovery of novel drugs, the exploration of drug combination therapies and the identification of drug resistance or side effects. PharmGWAS is available at https://ngdc.cncb.ac.cn/pharmgwas.

PMID:37831083 | DOI:10.1093/nar/gkad832

MMW Fortschr Med. 2023 Oct;165(18):13. doi: 10.1007/s15006-023-3071-0.

NO ABSTRACT

PMID:37828306 | DOI:10.1007/s15006-023-3071-0

Cureus. 2023 Sep 10;15(9):e44984. doi: 10.7759/cureus.44984. eCollection 2023 Sep.

ABSTRACT

INTRODUCTION: Anticancer agents are responsible for a majority of adverse drug reactions (ADRs) in cancer patients. ADR reporting with anticancer drugs is very rare in India due to the lack of awareness and knowledge about the Pharmacovigilance Programme of India. Hence, this study was done to assess the pattern of ADRs with anticancer agents in cancer patients and to increase awareness about ADR monitoring among healthcare professionals.

MATERIALS AND METHODS: This is an observational, retrospective and non-interventional study conducted in an ADR monitoring centre (AMC) in Govt. Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, North India. Voluntarily reported ADR forms with anticancer drugs as suspected drugs over a period of seven years from January 2016 to December 2022 were analyzed. Various parameters were analyzed, which include demographic details of the patients, type of ADR, department reporting ADR and suspected drug. Causality assessment, severity assessment and preventability assessment were done according to the World Health Organization Uppsala Monitoring Centre (WHO-UMC) scale, modified Hartwig and Siegel scale and modified Schumock and Thornton scale, respectively.

RESULTS: The maximum numbers of ADRs were reported in the age group of 41-60 years (68.29%) and in females (59.75%). The maximum number of ADRs was reported with the use of taxanes (docetaxel and paclitaxel) (24.39%), targeted drugs (geftinib, imatinib, bortezomib, bevacizumab, rituximab and pazopanib) (24.39%) and platinum co-ordination complexes (cisplatin, oxaliplatin and carboplatin) (17.07%). Majority of the ADRs reported were shivering and ADRs on the skin. Majority of the ADRs were probable (64.70%), mild in nature (85.29%), definitely preventable (45.58%) and probably preventable (45.58%).

CONCLUSION: ADR monitoring is needed to increase the outcome of anticancer drug treatment in cancer patients. The quality of treatment in cancer patients can be improved through the timely management of these ADRs. It is a need of the present era to inform healthcare professionals about the Pharmacovigilance Programme to increase the reporting of ADRs due to anticancer drugs.

PMID:37822427 | PMC:PMC10562879 | DOI:10.7759/cureus.44984

Drug Saf. 2023 Oct;46(10):1021-1037. doi: 10.1007/s40264-023-01342-z. Epub 2023 Oct 11.

ABSTRACT

BACKGROUND AND OBJECTIVE: Medication safety problems are common post-hospital discharge, and an important global healthcare improvement target. The Transfers of Care Around Medicines (TCAM) service was launched by a National Health Service Trust in the North-West of England, initially focusing on patients with new or existing Monitored Dosage Systems (MDS). The TCAM service is designed to enable the prompt transfer of medication information, with referrals made by hospitals at discharge to a named community pharmacy. This study aimed to explore the utilisation and impact of the TCAM service on medication safety.

METHODS: The evaluation included a descriptive analysis of 3033 anonymised patient referrals to 71 community pharmacies over a 1-year period alongside an assessment of the impact of the TCAM service on unintentional medication discrepancies and adverse drug events using a retrospective before-and-after study design. Impact data were collected across 18 general practices by 16 trained clinical pharmacists.

RESULTS: Most patient referrals (70%, 2126/3033) were marked as 'completed' by community pharmacies, with 15% of completed referrals delayed beyond 30 days. Screening of 411 patient records by clinical pharmacists yielded no statistically significant difference in unintentional medication discrepancies or adverse drug event rates following TCAM implementation using a multivariable regression analysis (unintentional medication discrepancies adjusted odds ratio = 0.79 [95% confidence interval 0.44-1.44, p = 0.46]; and adverse drug events adjusted odds ratio = 1.19 [95% confidence interval 0.57-2.45, p = 0.63]), although there remained considerable uncertainty.

CONCLUSIONS: The TCAM service facilitated a number of community pharmacy services offered to patients with monitored dosage systems; but the impact of the intervention on unintentional medication discrepancies and adverse drug event rates post-hospital discharge for this patient group was uncertain. The results of this exploratory study can inform the ongoing implementation of the TCAM service at hospital discharge and highlight the need to understand service implementation in different contexts, which may influence its impact on medication safety.

PMID:37819463 | PMC:PMC10584716 | DOI:10.1007/s40264-023-01342-z

J Pak Med Assoc. 2023 Sep;73(9):1891-1893. doi: 10.47391/JPMA.6322.

ABSTRACT

Word Health Organization declared COVID 19 infection as pandemic in 2020. Since then different countries had started working on vaccination. After multiple trials different vaccinations got approved. The first vaccine to be received in Pakistan was Sinopharm and was provided to nearly all health care professionals on priority basis. The safety profile of different vaccines were satisfactory and there were very few side effects reported till date. We are reporting the first case in Pakistan where a female health care professional developed vaccination induced deranged liver function test with delayed but complete recovery. Extensive workup was done to rule out all other differentials of deranged liver function test.

PMID:37817706 | DOI:10.47391/JPMA.6322

Ophthalmology. 2023 Oct 9:S0161-6420(23)00716-9. doi: 10.1016/j.ophtha.2023.10.004. Online ahead of print.

ABSTRACT

We classified drug-induced uveitis related to Immune Checkpoint inhibitors (ICIs) and MAP-kinase pathway inhibitors (MAPKi), including BRAF-inhibitors (BRAFi) and MEK-inhibitors (MEKi), according ophthalmological examination. Cases were retrieved from the French pharmacovigilance database (FPVD) which included all adverse drug reactions (ADR) registred by the French Regional Pharmacovigilance Network. We collected 113 cases of drug-induced uveitis (46 ICI-related and 67 MAPKi-related). The classification analysis identified four clusters. ICI were associated with anterior, posterior and panuveitis with severe manifestations such as retinal vasculitis and optic neuropathy. BRAFi were associated with anterior and panuveitis. MEKi inhibitors were associated with early serous-retinal detachment.

PMID:37820932 | DOI:10.1016/j.ophtha.2023.10.004

Clin Cancer Res. 2023 Oct 11. doi: 10.1158/1078-0432.CCR-23-2005. Online ahead of print.

ABSTRACT

BACKGROUND: Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC.

METHODS: Patients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2-6, 9-13, and 16-20 of each 21-day cycle. Pre-treatment tumor biopsies were obtained from each patient for correlative studies and generation of organoid cultures for drug sensitivity testing and biomarker analyses. >Results: Eleven patients with PDAC were enrolled in the expansion cohort between August 27, 2020 and July 30, 2021. Four patients (36%) experienced drug-related grade 3 adverse events. No objective radiological responses were observed, and all patients discontinued the trial by 3.2 months. In contrast to the lack of efficacy observed in patients, organoid cultures derived from biopsies procured from two patients demonstrated strong sensitivity to the gemcitabine/LY2880070 combination and showed treatment-induced upregulation of replication stress and DNA damage biomarkers, including pKAP1, pRPA32, and γ-H2AX, as well as induction of replication fork instability.

CONCLUSIONS: No evidence of clinical activity was observed for combined low dose gemcitabine and LY2880070 in this treatment refractory PDAC cohort. However, the gemcitabine/LY2880070 combination showed in vitro efficacy, suggesting that drug sensitivity for this combination in organoid cultures may not predict clinical benefit in patients.

PMID:37819936 | DOI:10.1158/1078-0432.CCR-23-2005

Haemophilia. 2023 Oct 11. doi: 10.1111/hae.14880. Online ahead of print.

ABSTRACT

INTRODUCTION: Emicizumab mimicking the cofactor function of activated factor VIII (FVIII) restores haemostasis.

METHODS: This nationwide observational study aimed to retrospectively investigate efficacy, safety, and cost in 1 year before and up to 3 years after emicizumab prophylaxis for haemophilia A (HA) patients with FVIII inhibitors.

RESULTS AND DISCUSSION: A total of 39 severe HA patients with a median age of 23.0 years were enrolled. The median historical peak FVIII inhibitor titre was 174.2 BU/mL with an interquartile range of 56.5-578.8 BU/mL. The median annualized bleeding rate reduced from 24 to 0 events in the first year after emicizumab prophylaxis (p < .01) and sustained in the second and third years. The median annualized joint bleeding rate reduced to 0 and maintained up to 3 years (p < .01). Twenty-seven patients (69.2%) had target joints before emicizumab prophylaxis and only seven patients (17.9%) of them had target joints after prophylaxis. Medical costs, including cost of haemostatic therapy, frequency of outpatient department visits, emergency room visits and hospital admission, were significantly reduced after emicizumab prophylaxis (p < .01). FVIII inhibitor titre decreased after emicizumab prophylaxis. Overall, three (7.7%) patients experienced 202 grade 1 drug-related adverse events after emicizumab prophylaxis. No serious adverse events were reported during emicizumab prophylaxis period. The adherence to emicizumab prophylaxis was 100% up to 3 years.

CONCLUSIONS: HA patients with FVIII inhibitors treated with emicizumab prophylaxis resulted in a significant reduction in treated bleeds and associated costs. No new safety events were observed.

PMID:37819166 | DOI:10.1111/hae.14880

J Pediatric Infect Dis Soc. 2023 Oct 10:piad078. doi: 10.1093/jpids/piad078. Online ahead of print.

ABSTRACT

BACKGROUND: IMPAACT 2014 study is a phase I/II, multicenter, open-label, non-randomized study of doravirine (DOR) co-formulated with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) as fixed dose combination (DOR FDC) in adolescents with HIV-1. We report the efficacy, safety, and tolerability of DOR FDC through 96 weeks.

METHODS: Participants were adolescents aged 12 to <18 years who weighed at least 45 kg and who were either antiretroviral (ARV)-naïve or virologically suppressed without documented resistance mutations to DOR/3TC/TDF. The efficacy endpoint was the proportion of participants with HIV-1 RNA <40 copies/mL assessed at week 48 and 96 using the observed failure approach. Safety and tolerability outcomes were incidence of adverse events and treatment discontinuations.

RESULTS: A total of 45 adolescents, median age 15 (range, 12 - 17) years, 58% females, were enrolled, 2 (4.4%) participants were ARV-naïve. Of the 45 participants, 42 (93.3%) completed the study and 41 (91.1%) completed study treatment. At week 48, 41/42 (97.6%; 95% confidence interval [CI], 87.4 - 99.9) and week 96, 37/40 (92.5%; 95% CI, 79.6 - 98.4) participants had achieved or maintained HIV-1 RNA <40 copies/mL. There were no treatment-related discontinuations due to adverse events and no drug-related adverse events ≥ grade 3 or deaths.

CONCLUSIONS: We found once daily dosing of DOR FDC to be safe and well tolerated for maintaining viral suppression through 96 weeks in adolescents living with HIV-1.

PMID:37815035 | DOI:10.1093/jpids/piad078

Per Med. 2023 Sep;20(5):417-424. doi: 10.2217/pme-2023-0033. Epub 2023 Oct 9.

ABSTRACT

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10-7.24) and the adjusted OR was 5.39 (95% CI: 1.69-17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.

PMID:37811569 | DOI:10.2217/pme-2023-0033

Nat Commun. 2023 Oct 9;14(1):6243. doi: 10.1038/s41467-023-41893-4.

ABSTRACT

G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency, and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy, and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity, and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences.

PMID:37813859 | PMC:PMC10562414 | DOI:10.1038/s41467-023-41893-4

J Patient Rep Outcomes. 2023 Oct 9;7(1):99. doi: 10.1186/s41687-023-00640-5.

ABSTRACT

BACKGROUND: Patient-reported outcomes (PROs) are getting widely implemented, but little is known of the impact of applying PROs in specific cancer diagnoses. We report the results of a randomized controlled trial (RCT) of the active use of PROs in patients with locally advanced or metastatic bladder cancer (BC) undergoing medical oncological treatment (MOT) with focus on determining the clinical effects of using PROs during chemo- or immunotherapy compared to standard of care.

METHODS: We recruited patients from four departments of oncology from 2019 to 2021. Inclusion criteria were locally advanced or metastatic BC, initiating chemo- or immunotherapy. Patients were randomized 1:1 between answering selected PRO-CTCAE questions electronically once weekly with a built-in alert-algorithm instructing patients of how to handle reported symptoms as a supplement to standard of care for handling of side effects (intervention arm (IA)) vs standard procedure for handling of side effects (control arm (CA)). No real-time alerts were sent to the clinic when PROs exceeded threshold values. Clinicians were prompted to view the completed PROs in the IA at each clinical visit. The co-primary clinical endpoints were hospital admissions and treatment completion rate. Secondary endpoints were overall survival (OS), quality of life (EORTC's QLQ-C30 and QLQ-BLM30) and dose reductions.

RESULTS: 228 patients with BC were included, 76% were male. 141 (62%) of the patients had metastatic disease. 51% of patients in the IA completed treatment vs. 56% of patients in the CA, OR 0.83 (95% CI 0.47-1.44, p = 0.51). 41% of patients in the IA experienced hospitalization vs. 32% in the CA, OR 1.48 (95% CI 0.83-2.65, p = 0.17). OS was comparable between the two arms (IA: median 22.3mo (95% CI 17.0-NR) vs. CA: median 23.1mo (95% CI 17.7-NR). Patient and clinician compliance was high throughout the study period (80% vs 94%).

CONCLUSIONS: This RCT did not show an effect of PRO on completion of treatment, hospitalizations or OS for BC patients during MOT despite a high level of patient and clinician compliance. The lack of real-time response to alerts remains the greatest limitation to this study.

PMID:37812306 | DOI:10.1186/s41687-023-00640-5

BMC Med. 2023 Oct 9;21(1):388. doi: 10.1186/s12916-023-03089-x.

ABSTRACT

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM.

METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded.

RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group.

CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM.

TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.

PMID:37814306 | DOI:10.1186/s12916-023-03089-x

Am J Nephrol. 2023 Oct 9. doi: 10.1159/000534484. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperphosphatemia in CKD patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis.

TRIAL DESIGN: This is an open-label active-drug-controlled multicenter randomized study.

METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio receiving either ferric citrate or sevelamer carbonate respectively for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated at every two weeks. Frequency and severity of adverse events were recorded.

RESULTS: 217 (90.4%) patients completed the study, with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59±0.54mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (P>0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group were significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) in the sevelamer carbonate group experienced drug-related TEAEs, most were mild and tolerable. Common drug-related TEAEs were "gastrointestinal disorders", including diarrhea (12.9% vs. 2.5%), feacal discoloration (14.7% vs. 0%), and constipation (1.7% vs. 7.4%) in ferric citrate and sevelamer carbonate group respectively.

CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

PMID:37812931 | DOI:10.1159/000534484

Clin Exp Rheumatol. 2023 Oct 5. doi: 10.55563/clinexprheumatol/rq4k3u. Online ahead of print.

ABSTRACT

OBJECTIVES: The approval of TNF-a inhibitors (TNFi) was a breakthrough in the treatment of ankylosing spondylitis (AS). Although also effective in psoriasis, drug-related adverse events of onset of psoriasiform skin lesions - paradoxical psoriasis (PP) under TNFi have been reported.

METHODS: We performed an electronic data search in MEDLINE via Pubmed and Cochrane library scientific databases from inception to January 2023, following the PRISMA guidelines. We assessed the distinct characteristics and frequency of risks for PP appearance in AS patients treated with different TNFi.

RESULTS: PP was found in 0.5-1% of TNFi-treated AS patients and the latency period was 2-11 months. The safest TNFi in terms of PP induction was certolizumab, whereas the one most commonly associated with PP was infliximab.

CONCLUSIONS: PP is an uncommon adverse reaction to TNFi treatment in AS patients and responds well to drug withdrawal. More large data studies need to be conducted though, to shed light on PP nature and management.

PMID:37812484 | DOI:10.55563/clinexprheumatol/rq4k3u

Crit Care Explor. 2023 Oct 5;5(10):e0986. doi: 10.1097/CCE.0000000000000986. eCollection 2023 Oct.

ABSTRACT

OBJECTIVES: To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19).

DESIGN: Double-blind, randomized clinical trial.

SETTING: Two ICUs at an academic medical center.

PATIENTS/SUBJECTS: Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support.

INTERVENTIONS: SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days.

MEASUREMENTS AND MAIN RESULTS: We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial.

LIMITATIONS: The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial.

CONCLUSIONS: Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis.

PMID:37811130 | PMC:PMC10558223 | DOI:10.1097/CCE.0000000000000986

Ann Med Surg (Lond). 2023 Sep 1;85(10):5232-5234. doi: 10.1097/MS9.0000000000001231. eCollection 2023 Oct.

ABSTRACT

INTRODUCTION: Rhabdomyolysis may arise due to traumatic or non-traumatic causes leading to muscle injury. However, increased statin use has raised drug-related side effects like statin-related muscle damage.

CASE REPORT: A 74-year-old male with liver cirrhosis secondary to alcohol was prescribed atorvastatin for hyperlipidemia. He developed muscle tenderness and decreased muscle power 2 weeks following statin therapy, evident with a creatine phosphokinase level of more than 22 000 IU/l. The urinalysis also revealed positive for blood. Hence, atorvastatin was ceased. The patient's laboratory parameters improved significantly, implying atorvastatin is the causative agent for rhabdomyolysis.

DISCUSSION: Statins are usually safe and well-tolerated drugs; however, skeletal muscle symptoms occur in ~5-10% of patients. The risk factor for statin-induced muscle injury includes advanced age, drug-altering statin plasma level, liver disease, or chronic kidney disease. Moreover, the hepatic level of CYP450 and its CYP3A4 isoform are altered in chronic liver diseases. CYP3A4 isoenzyme and its activity declines in hepatic cirrhosis patients.

CONCLUSION: Statins are generally prescribed for hyperlipidemia and primary and secondary prevention in high-risk cardiovascular diseases. However, several risk factors alter statin metabolism, causing statin-induced muscle injury. Thus, despite several studies suggesting otherwise, special precautions should be taken in patients with chronic liver disease.

PMID:37811121 | PMC:PMC10553173 | DOI:10.1097/MS9.0000000000001231