First Year Of Treatment Research Articles

Management of clozapine-associated neutropenia

SUMMARY Clozapine is the only evidence-based intervention for treatment-resistant schizophrenia. One of the drug's most well-known and potentially fatal adverse effects is agranulocytosis (severe neutropenia). Hence, regular blood tests are an essential component of clozapine treatment. This article presents a narrative review of the history, incidence, potential aetiology and management of clozapine-associated neutropenia. It gives an overview of clozapine monitoring requirements, including those for benign ethnic neutropenia. We point to the growing body of evidence that the risk of clozapine-induced agranulocytosis is mostly confined to the first year of treatment and that the risk of fatality is considerably lower than previously assumed. Given the absence of alternative evidence-based interventions for treatment-resistant schizophrenia, we suggest that rechallenging with clozapine should be considered in most patients with clozapine-associated mild to moderate neutropenia who do not respond to other treatments. A more careful risk–benefit analysis is needed in cases of severe neutropenia (agranulocytosis).

BCG Medac® for the treatment of non-muscle-invasive bladder tumors: adverse events and predictive factors for tolerance.

Adjuvant treatment with endovesical BCG instillations after resection of a bladder urothelial tumor remains the gold standard for intermediate- or high-risk non-muscle-invasive tumors. However, it is associated with frequent and sometimes serious adverse events (AEs). To comprehensively assess the frequency, intensity, and potential risk factors of BCG instillation AEs following the field experience of a single French center using only the Medac® BCG. A database obtained through a query to the Medical Information Department identified 127 patients who received 1498 Medac® BCG instillations from July 2016 to July 2021. The study focused on the instillations performed in the 1st year (induction treatment and the first two maintenance cycles). Data included demographics, tumor characteristics, treatment conduct and adverse events and their characteristics. Logistic regression completed the descriptive statistics to search for associations between AEs and potential risk factors. Of the 127 patients, 81% had at least one AE. AEs concerned the genitourinary sphere in 80% of cases. The proportion of side effects classified as severe was 4%. BCG treatment was discontinued in 41 patients (32.2% of patients), the main reason being the occurence of AEs (21 out of 41 patients, i.e. 51%). Age, diabetes, active smoking, previous BCG instillations, residual tumor at 2nd look TURB, use of ofloxacin and non-negative urine culture were significantly associated to AEs. Conversely, gender, previous MMC instillation, stage, grade, 2nd look procedure and ASA score were not. Multivariate analysis showed that the presence of residual tumour at 2nd look and active smoking were independent predictive factors. However, these factors were not systematically found for all instillations. The analysis was also performed per instillation. Data on a total of 1498 BCG instillations were collected, with a median of 11 instillations per patient. Of these instillations, 29.6% resulted in AEs. In addition, 125 instillations (8%) were associated with more than one AE. A total of 569 AEs were recorded, with an average of 27.2% AEs per instillation. AEs led to the postponement of 16 instillations out of 93 (17%) in 15 patients. In our study, most patients who received endovesical instillations of BCG experienced AEs, mainly localized to the genitourinary sphere and of low severity. Discontinuation of BCG and serious AEs requiring more than monitoring or symptomatic treatment were not frequent during the first year of treatment. We found no robust predictor of AEs. The problems of predicting the efficacy of BCG on the one hand, and its tolerability on the other, remain unresolved and warrant a future sufficiently powered prospective study.

Discontinuation and reinitiation of mineralocorticoid receptor antagonists in patients with heart failure and reduced ejection fraction.

Mineralocorticoid receptor antagonists (MRA) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are underused. Point prevalent use has been described, but the kinetics of discontinuation and the extent of reinitiation have not been studied. Patients with HFrEF enrolled in the Swedish Heart Failure Registry between 2006 and 2021 were linked to the Prescribed Drug Register. The rate of discontinuation during the first year of treatment and reinitiation the year after discontinuation were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to assess the predictors of discontinuation. Of 11 474 MRA new users, 71% remained on therapy at 1 year. Baseline characteristics independently associated with discontinuation were: estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34-2.27), hyperkalaemia (HR 1.73, 95% CI 1.25-2.40), eGFR 30-60 ml/min/1.73 m2 (HR 1.51, 95% CI 1.37-1.66), age ≥80 years (HR 1.26, 95% CI 1.10-1.43), enrolment as inpatient (HR 1.25, 95% CI 1.14-1.38), a diagnosis of atrial fibrillation (HR 1.24, 95% CI 1.10-1.39), living alone (HR 1.23, 95% CI 1.13-1.34), ischaemic heart disease (HR 1.20, 95% CI 1.09-1.31), anaemia (HR 1.17, 95% CI 1.07-1.29), diabetes mellitus (HR 1.15, 95% CI 1.04-1.27) and New York Heart Association class III-IV (HR 1.13, 95% CI 1.02-1.24). Reinitiation within a year occurred in 46% of cases, mostly within 3 months after discontinuation. Among patients with HFrEF initiated on MRA, 71% remained on therapy at 1 year. Discontinuation occurred early and was more common in patients with advanced kidney disease, hyperkalaemia, lack of follow-up in specialty care, more severe heart failure, comorbidities, and markers of sociodemographic frailty. Among those who discontinued, almost half reinitiated treatment the year following discontinuation.

Comparison of the Safety and Efficacy of Ustekinumab and Vedolizumab in Patients with Crohn's Disease: A Systematic Review and Meta-Analysis of Propensity Score Matched Cohort Studies.

Background: Ustekinumab and vedolizumab represent both valid therapeutic options in patients with Crohn's Disease. Data comparing the safety and efficacy of these drugs are indirect, with conflicting results reported. We aim to conduct a systematic review and metanalysis to assess the safety and effectiveness profile of ustekinumab and vedolizumab in patients with Crohn's Disease, including only studies that applied propensity scores to reduce confounding bias. Methods: We identified 59 reports that compared ustekinumab and vedolizumab after a propensity score match analysis, of which 16 were assessed for eligibility, and finally, ten retrospective studies were included. The main outcomes considered were clinical steroid-free remission at 14 ± 4, 24 ± 4, and 52 ± 4 weeks, drug discontinuation rate, adverse events, serious infections, and hospitalization during the first year of treatment. Results: A total of 4398 patients were treated with ustekinumab (n = 2774, 63.1%) or vedolizumab (1624, 36.9%). Steroid-free clinical remission was not significantly different between ustekinumab and vedolizumab at 12 ± 4 weeks (OR 1.31, 95%CI 0.88-1.94, p = 0.180), at 24 ± 4 weeks (OR 1.18, 95%CI 0.79-1.75, p = 0.420), and at 52 ± 4 weeks (1.35, 95%CI 0.91-2.01, p = 0.140). In patients receiving ustekinumab, the rate of adverse events (OR 0.54, 95%CI 0.35-0.83, p = 0.005), infection (OR 0.61, 95%CI 0.47-0.80, p < 0.001) and the need of hospitalization at 1-year (OR 0.68, 95%CI 0.58-0.80, p < 0.001) appeared to be lower. Conclusion: Ustekinumab and vedolizumab do not significantly differ in inducing and maintaining clinical steroid-free remission, while ustekinumab was associated with a lower risk of serious infections and hospitalization during the first year of treatment.

Incremental hemodialysis transition in veterans and nonveterans with kidney failure.

Initiation of hemodialysis treatment with a thrice-weekly prescription is currently the standard of care irrespective of patients' residual kidney function (RKF), comorbidities, and preferences. Each year ∼12 000 Veterans with advanced kidney disease progress to end-stage kidney disease (ESKD) requiring dialysis and comprise greater than 10% of the US incident ESKD population. Dialysis is costly and is associated with impaired health-related quality of life (HRQOL) and high mortality risk, especially in the first year of treatment. Evidence suggests an incremental dialysis transition using twice-weekly hemodialysis provides various benefits, including more dialysis-free time, longer RKF preservation, less vascular access damage, and lower patient burden. Pragmatic studies are needed to inform the efficacy and safety of incremental hemodialysis as a personalized dialysis regimen, and could inform its consideration as a conservation strategy during times of supply shortages. Broadly implementing twice-weekly hemodialysis could also potentially allow more Veterans to receive care within VA-based dialysis units. The VA IncHVets Trial is a pragmatic, multicenter, randomized controlled trial comparing the efficacy and safety of twice-weekly incremental vs. thrice-weekly hemodialysis among Veterans transitioning to ESKD. Further research is needed to determine whether incremental hemodialysis is well tolerated, effective, and facilitates a more favorable transition to dialysis.

Impact of anti-VEGF treatment-free interval during the first year on 5-year outcomes in eyes with branch retinal vein occlusion.

This study aims to analyze the impact of longest treatment-free interval (TFI) between anti-vascular endothelial growth factor (anti-VEGF) injections during the first year of treatment on 5-year best-corrected visual acuity (BCVA) and recurrence of macular edema (ME) in eyes with ME secondary to branch retinal vein occlusion (BRVO). A retrospective study including eyes with BRVO, minimum of 5-year follow-up, and available optical coherence topography (OCT) scans. Eyes underwent anti-VEGF loading dose therapy and were treated and monitored with an OCT-guided PRN regimen. Those with a history of ocular comorbidities were excluded. Total of 60 patient eyes, with 40 females and average age of 71.75 ± 11.07 years. TFI among eyes was 1 month (20%); > 1-2 months (23%); > 2-3 months (18%); > 3-4 months (17%), and >4 months (22%). Forty-three (72%) eyes experienced ME recurrence during the five-year period. Multivariate linear regression shows that TFI (-0.02 [-0.03-0.00], p = 0.021) and baseline BCVA (0.37 [0.08-0.66], p = 0.014) are significant predictors of 5-year BCVA. TFI (Cox Proportional Hazard Ratio 1.34 [1.04-1.72], p = 0.023) and number of injections in the first year (Cox Proportional Hazard Ratio 1.76 [1.01-3.06], p = 0.045) were significant predictors of ME recurrence. Gender, age, type of injection, BCVA, and CMT did not influence recurrence. For eyes receiving anti-VEGF injections to treat ME secondary to BRVO, TFI is a significant predictor of 5-year BCVA and ME recurrence according to regression models. This study suggests more ME recurrence may be due to increased TFI or indicate more injections needed to treat severe BRVO.

Sorafenib or anthracycline-based chemotherapy for progressive desmoid tumors.

Desmoid tumors can cause morbidity due to local invasion, potentially being fatal when fast growth compromises vital structures. In this context, a timely treatment response is required. This study aims to compare the activity of sorafenib and anthracycline-containing regimens during the first year of treatment. The authors conducted a multi-institutional retrospective analysis of desmoid tumor patients treated with either sorafenib or an anthracycline-containing regimen over 1 year. The primary end point was the overall response rate (ORR). The secondary end points were time to response (TTR), progression-free survival (PFS), and adverse events. From 2005 to 2022, 80 patients received sorafenib and 51 received an anthracycline-containing regimen with similar baseline characteristics. The 1-year ORR was 37% for anthracycline and 13% for sorafenib (p=.016). Median best response was -9% (range, -73 to 51) for anthracycline and -4% (range, -69 to 126) for sorafenib. Median TTR was 5.6 months (95% confidence interval [CI], 3.4-7.8) for anthracycline and 8.7 months (95% CI, 6.3-11.1) for sorafenib (p=.2). One-year PFS was 73% (95% CI, 60-86) for anthracycline and 59% (95% CI, 47-71) for sorafenib (p=.3). Common grade 1-2 adverse events for sorafenib were hand-foot syndrome (40%), diarrhea (25%), and fatigue (22%); for anthracycline, they were nausea (31%), fatigue (16%), and rash (14%). Grade 3 events were higher in the anthracycline group, 27% versus 14% (p<.05). Anthracycline-based therapy provided a greater 1-year response rate than sorafenib but was associated with a higher rate of serious adverse events. Higher-risk desmoid tumors, which need a more timely response, might benefit from anthracycline-based therapies, whereas average-risk tumors could benefit from sorafenib.

NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)

Abstract BACKGROUND Despite favorable long-term survival, ongoing disease and treatment-related morbidity substantially impact the HRQOL of patients with pLGG. Tovorafenib is a selective, CNS-penetrant, type II RAF inhibitor. Results from the ongoing FIREFLY-1 (NCT04775485) phase 2 study (Kilburn LK, et al. Nat Med. 2023) showed clinically meaningful responses and a manageable safety profile in pLGG. Vision remained stable or improved in 89% of evaluable patients with optic pathway gliomas (Nysom K, et al. Neuro-Oncol. 2023). METHODS FIREFLY-1 arm 1 patients 6 months–25 years of age with RAF-altered r/r pLGG received tovorafenib 420 mg/m2 weekly (600 mg max) in 28-day cycles. Exploratory measures included longitudinal assessment of PedsQL in patients ≥2 years of age. PedsQL 3.0 Cancer Module child self-reports Total Score and 8 subscales were used to assess HRQOL from 0 (worst)–100 (fewer problems/symptoms) (as of December 22, 2022) baseline (BL) to cycle 13 (C13) in patients ≥5 years of age. RESULTS For the PedsQL 3.0 Cancer Module, 51 completed self-reports at BL, and 32 at C13 due to continued attrition over time. Median Total Score was 81.5 (range: 46.3-100) at BL and 85.2 (range: 50-100) at C13. At C4, 16% worsened (decrease &amp;gt;10 points) and 11% improved (increase &amp;gt;10 points); by C13, 11% worsened and 33% improved. For Cognitive Problems, patients scored a median of 75 (range: 5-100) at BL and 85 (range: 20-100) at C13, with 11% and 26% improved at C4 and C13, respectively. A similar trend was seen with Nausea. Pain and Hurt remained even throughout (median: 87.5). Treatment Anxiety was not a major concern (median: 100, C1-C13); Procedural Anxiety improved over time (median: 58.3 BL; 79.2 at C13). CONCLUSIONS HRQOL generally remained stable, or improved, in the majority of patients with r/r pLGG during the first year of treatment with tovorafenib.

Weight Loss After Receiving Anti‐Obesity Medications and Gout Among Individuals With Overweight and Obese: A Population‐Based Cohort Study

ObjectiveWeight loss is conditionally recommended for gout management; however, its impact on incident gout and recurrent gout flares among individuals who were overweight and obese remains unknown. We investigate the relationship between weight loss rate following treatment with anti‐obesity medications and the risk of incident gout and recurrent gout flares among individuals who were overweight or obese.MethodsUsing data from the Health Improvement Network, we selected individuals aged 18 and older who were overweight or obese and started anti‐obesity medication. We emulated a target trial to examine the association of different weight loss rates, slow (2%–5%), moderate (5%–10%), or fast (≥10%), within the first year of treatment with incident gout and recurrent gout flares during a 5 year follow‐up period.ResultsAmong 131,000 participants without gout being treated with orlistat, the 5‐year risk of incident gout was 1.6% for those with weight gain or stability, compared with 1.5%, 1.3%, and 1.2% for those with slow, moderate, and fast weight loss, respectively. Compared with the group with weight gain or stability, the hazard ratios were 0.91 (95% confidence interval [CI] 0.81–1.01), 0.82 (95% CI 0.72–0.92), and 0.73 (95% CI 0.62–0.86) for those with a slow, moderate, and fast rate of weight loss, respectively. Similar results were observed for the recurrent gout flares among 3,847 individuals with overweight or obese with gout treated with orlistat.ConclusionA higher rate of weight loss after receiving treatment with orlistat within 1 year was associated with lower risks of incident gout and lower rates of recurrent gout flares among overweight or obese people.image

NCOG-41. COMPARATIVE ANALYSIS OF MORTALITY AND SHORT-TERM SIDE EFFECTS IN PATIENTS WITH GLIOBLASTOMA MULTIFORME TREATED WITH TEMOZOLOMIDE VERSUS TEMOZOLOMIDE PLUS BEVACIZUMAB CHEMOTHERAPY

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor in adults with limited treatment options and poor prognosis. Temozolomide (TMZ) chemotherapy is the standard treatment for GBM, but alternative therapies have shown limited success. Bevacizumab (BEV), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), is used to restrict GBM growth and spread. This study evaluates the efficacy of combining TMZ with BEV compared to TMZ alone in managing GBM. METHODS A retrospective cohort study was conducted using TriNetX database data, focusing on patients diagnosed with GBM and receiving chemotherapy. Cohorts were defined by treatment: TMZ plus BEV versus TMZ alone. Propensity-score matching balanced baseline characteristics, including demographics and health conditions. Primary outcomes included mortality rates and short-term side effects within the first year of treatment, such as cognitive communication deficits, headache, dizziness, insomnia, and nausea/vomiting. RESULTS After matching, 922 patients were included in each cohort. There were no significant demographic differences post-matching. The mortality rate was higher in the TMZ plus BEV group compared to TMZ alone (51.30% vs. 36.98%, RR: 1.387, 95% CI: 1.249-1.541). However, TMZ plus BEV was associated with a lower incidence of cognitive communication deficits (1.95% vs. 4.34%, RR: 0.45, 95% CI: 0.26-0.779) and dizziness (7.27% vs. 10.52%, RR: 0.691, 95% CI: 0.513-0.93). No significant differences were found in headache, insomnia, or nausea/vomiting rates between the groups. CONCLUSION This study indicates that combining bevacizumab with temozolomide may increase mortality in GBM patients but reduce certain side effects such as cognitive deficits and dizziness. These findings emphasize the need to carefully consider the benefits and risks of different chemotherapy regimens for GBM and highlight the necessity for further research to optimize treatment strategies and improve patient outcomes.

Long-term persistence with secukinumab in patients with moderate-to-severe psoriasis

ObjectiveThe aim of this study was to evaluate the real-world persistence, effectiveness, and safety of secukinumab in adult patients with moderate-to-severe psoriasis in two different hospitals. MethodsRetrospective cohort study that used registries and medical records from 2 different hospitals (February 2015–March 2024). Adults with moderate-to-severe psoriasis who initiated secukinumab treatment were identified and followed-up until March 2024, or disenrollment. Baseline demographic and clinical characteristics studied included sex, age at diagnosis, weight, prior failed treatments, duration of treatment and psoriasis area severity index (PASI) score. Adherence was measured using medication possession ratio (MPR); patients with MPR ≥ 80% were considered adherent. Persistence, effectiveness, safety, and dosage regimen of secukinumab were collected. Kaplan–Meier analysis was used to estimate secukinumab persistence using 1-year intervals. ResultsA total of 88 patients with moderate-to-severe psoriasis were included, of whom 45 (51.1%) had not received prior biological treatment. Baseline PASI score was 15.0 ± 2.9 and patients received 1.4 ± 0.8 prior biological treatments. The most common previous biological treatments included anti-TNFα (60.5%) and ustekinumab (20.9%). 34 (38.6%) patients discontinued secukinumab treatment due to the following reasons.19 (21.5%) due to a lack of effectiveness, 8 (9.2%), due to achieve only a partial response, and 7 (7.9%) due to adverse effects. Secukinumab persistence was 61.5 ± [21.7] months for all patients. When performing a subgroup analysis, non-naïve patients obtained a persistence of 61.5 ± [12.4] months followed by 54.1 ± [14.8] months for naïve patients (p = .804). Secukinumab persistence at 1 year, 2 years, and 3 years was 72.7%, 51.1%, and 39.8%, respectively. ConclusionsSecukinumab demonstrated persistence in more than 70% of patients with moderate to severe psoriasis after the first year of treatment.

Long-Term Efficacy and Safety of Bimekizumab and Other Biologics in Moderate to Severe Plaque Psoriasis: Updated Systematic Literature Review and Network Meta-analysis.

Biologic treatments have made complete skin clearance in moderate to severe plaque psoriasis a real possibility. Although clinical trials demonstrated the superiority of bimekizumab over secukinumab, adalimumab, and ustekinumab, direct comparisons with other biologics are not available. This systematic literature review (SLR) and network meta-analysis (NMA) aimed to evaluate the 1-year efficacy and safety of bimekizumab versus other biologic systemic therapies for moderate to severe plaque psoriasis. We conducted an SLR to retrieve published randomised controlled trials (RCTs) in patients with moderate to severe plaque psoriasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and PsycINFO on 13 January 2022. Two NMA types were used to analyse the long-term achievement of 100% improvement from baseline in Psoriasis Area and Severity Index (PASI100): (1) NMA of cumulative clinical benefits, based on the area under the curve, from week0 to 52; (2) multinomial NMA at weeks44‒60. Binomial NMA was used to evaluate long-term serious adverse events (SAEs). The SLR identified 38 RCTs, of which 19 were included in the NMA. Bimekizumab 320mg administered every 4weeks to week16 then every 8weeks (Q4W/Q8W) showed a greater cumulative average number of days of PASI100 response compared with all other biologics. These differences were statistically significant versus all biologics, except risankizumab 150mg. The multinomial NMA demonstrated that interleukin (IL)-17 and IL-23 inhibitors were the most efficacious treatments. No significant differences were found in long-term occurrence of SAEs. Bimekizumab 320mg Q4W/Q8W was superior to most other treatments in maintaining complete skin clearance during the first year of treatment. It demonstrated a greater cumulative average number of days with completely clear skin while displaying a comparable safety profile compared with all other biologics.

Effectiveness and Persistence of Anti-TNFα Treatment in Patients with Rheumatoid Arthritis - A 7 Years Real-World Cohort Study.

To describe the effectiveness and persistence of treatment with three anti-TNFα drugs, Infliximab, Etanercept, and Adalimumab, in patients with Rheumatoid Arthritis (RA) in a rheumatology center. A longitudinal, retrospective cohort study was conducted. Data were obtained from the health records of patients with RA who were followed up in a rheumatology center between 2011 and 2019 under a multidisciplinary healthcare model (MCM). The drugs used in this study were indicated according to the treatment guidelines for prescription. In order to follow-up of disease activity, at least three DAS28 reports for every analyzed year were used. The chi-square test and Fisher's exact test were used for statistical analyses of categorical variables. For the analysis of treatment persistence, the Kaplan-Meier method was used based on the recorded follow-up time of disease activity. One hundred and eighty-three RA patients included (80% women, median age 60 years), who received adalimumab (n = 56) (30.6%), etanercept (n = 64) (34.9%), or infliximab (n = 63) (34.4%) during the 7-year study period. A higher proportion of patients had moderate or high disease activity for all three anti-TNFα. In first-year treatment, 67% to 87% of the cohort achieved disease activity control and disease response to treatment. For the first three years, 95% to 98% of patients continued with the medications. In years 5th and 7th, the proportion of patients on medication was 80% to 90% and 42% to 54%, respectively. The efficacy and persistence of anti-TNF-α were similar among the three molecules. These findings regarding long-term persistence in treatment may be useful for therapeutic decision-making based on real-life cohort results.

Characterizing Nonarticular Pain at Early Rheumatoid Arthritis Diagnosis: Evolution Over the First Year of Treatment and Impact on Remission in a Prospective Real-World Early Rheumatoid Arthritis Cohort.

Our objective was to characterize nonarticular pain (NAP) at early rheumatoid arthritis (RA) diagnosis, the evolution over the first year of treatment, associations with active RA inflammation, and the impact on remission. This real-world, longitudinal multicenter cohort study observed participants with active early RA (symptoms <1 year and Clinical Disease Activity Index [CDAI] >2.8) enrolled between January 2017 and January 2022 who completed a body pain diagram over 1 year. Participants were grouped by prespecified definitions of NAP: (1) none, (2) regional, or (3) widespread. Rheumatologists performed joint counts. Descriptive statistics summarized the frequency and evolution of NAP patterns over 1 year. Chi-square tests compared the proportions of tender and/or swollen joints by the presence of pain in each NAP section. Multiadjusted generalized estimating equations regression models estimated associations of NAP patterns with remission outcomes. Participants (N = 392) were 70% female, with a mean ± SD age of 56 ± 14 years and mean ± SD symptoms duration of 5.1 ± 2.7 months. More than half reported NAP at baseline, with most (73%) presenting with regional NAP. Common patterns of regional NAP were axial (40%) and pain in upper quadrants (17%). A total of 43% of those with regional NAP persisted or worsened over 1 year, whereas 73% of those with widespread NAP resolved or improved. Joint inflammation was more frequently reported in areas with NAP versus areas without NAP. Regional and widespread NAP were associated with lower odds of reaching CDAI remission (adjusted odds ratio 0.42, 95% confidence interval 0.26-0.70 and adjusted odds ratio 0.30, 95% confidence interval 0.12-0.74), respectively. Regional NAP is common and persistent in early RA and impacts remission. RA activity may contribute to NAP. More attention to NAP in RA care is warranted.

Clinical characteristics and treatment efficacy in patients with primary severe IGF-1 deficiency treated with recombinant IGF-1.

To evaluate the clinical characteristics and treatment efficacy of patients with severe primary IGF-1 deficiency (PSIGFD) using a recombinant IGF-1 (rhIGF-1). To examine the clinical characteristics of patients with PSIGFD before starting treatment with a rIGF-1. To assess the height changes in patients with PSIGFD, before and after treatment with a rhIGF-1. To analyze the clinical characteristics, side effect frequency, and treatment efficacy with a rhIGF-1 analog in patients with PSIGFD. A retrospective analysis was conducted on patients with PSIGFD treated with the rhIGF-1 (mecasermin). Data were collected from patients' medical records, focusing on the impact of treatment on their growth and monitoring any side effects. The study showed that treatment with rhIGF-1 positively affects growth rate, especially in the first years of treatment. However, the growth rate decreases over time. The change in height from the beginning to the end of the treatment was 0.76 ± 0.64 SD, with the first quartile at 0.29 SD and the third quartile at 1.14 SD. During the treatment period, patients' average body mass increased by 0.37 ± 1.35 SD, with the first quartile at -0.33 SD and the third quartile at 0.92 SD. Side effects occurred in 50% of patients, with 40% of patients treated with rhIGF-1 experiencing hypoglycemia during treatment. Treatment with rhIGF-1 is effective in treating patients with PSIGFD, causing significant improvement in growth, but requires continuous monitoring and treatment adjustment.

Long-term phenobarbital treatment is effective in working-age patients with epilepsy in rural Northeast China: a 10-year follow-up study.

Effective management of epilepsy in working-age patients is essential to reduce the burden on individuals, families, and communities. This study aimed to assess the long-term efficacy of phenobarbital (PB) in working-age patients with epilepsy in rural Northeast China and identify the risk factors for seizures during treatment. Patients aged 18-65 years diagnosed with convulsive epilepsy in rural areas of Jilin Province between 2010 and 2024 were included, and demographic and clinical data were recorded. Seizure frequency, self-efficacy, adherence, and adverse events (AEs) were assessed monthly. Of the 3,568 participants, 288 (8.1%) withdrew from the study and 159 (4.5%) died. During the first year of treatment, 75.2% of patients experienced a ≥50% reduction in seizure frequency compared with baseline (considered as treatment effectiveness); 53.7% of patients were seizure-free. By the tenth year, 97.7% of patients showed treatment effectiveness, and 89.6% were seizure-free. Self-efficacy was improved in 37.8% of patients in the first year and in 72% of patients by the tenth year. The independent risk factors for seizures during treatment were higher baseline seizure frequency [odds ratio (OR) = 1.431, 95% confidence interval (CI): 1.122-1.824], presence of multiple seizure types (OR = 1.367, 95% CI: 1.023-1.826), and poor adherence (OR = 14.806, 95% CI: 3.495-62.725), with significant differences observed in the first, third, and fifth years. The most commonly reported AEs were drowsiness (43.3%), dizziness (25.0%), and headaches (17.0%), most of which were mild and decreased over time. Age at enrollment was the only factor influencing withdrawal (hazard ratio = 0.984, 95% CI: 0.973-0.996, p = 0.010), with a substantial number of patients who withdrew (32.6%) relocating for work. Cardiovascular disease was the primary cause of death, and age at enrollment was the only risk factor (hazard ratio = 1.026, 95% CI: 1.009-1.043, p = 0.002). Working-age adults with epilepsy demonstrated a favorable response and tolerability to PB monotherapy. Baseline seizure frequency, seizure type, and adherence consistently predicted prognosis throughout the treatment period. Withdrawal was mainly explained by work-related pressures in this age group. Therefore, it is essential to implement interventions that support patient adherence to therapy and maintain stable regimens.

Efficacy and safety of cladribine tablets in multiple sclerosis in real-world clinical practice

Cladribine has a well-defined activity against lymphocytes, leading to their selective depletion.Objective: to determine the efficacy and safety of cladribine in the treatment of multiple sclerosis (MS) in real-world clinical practice.Material and methods. The study involved 82 patients (57 women and 25 men, mean age 36.4±9.3 years) with a disease duration of 2.2±1.5 years. Seven (9%) patients had secondary progressive MS (SPMS), 6 (7%) had rapidly progressive MS (RPMS) and 69 (84%) had highly active MS (HAMS). According to the instructions for use, oral therapy with cladribine was administered in two short courses (up to 10 days per year) to achieve a long-term effect on the immune system. The dose of cladribine was calculated based on the body weight.Results. The average frequency of exacerbations per year before starting therapy was 1.6, while it decreased to 0.2 during cladribine therapy. An exacerbation was observed in 18 patients (22%) at the end of the first course of cladribine treatment and in one patient (2.6%) after the second treatment course. Thus, the number of exacerbations decreased by 78% after the first year of treatment and by 97.4% after the second year of treatment. The mean EDSS score was 3.2±2.5 points before the start of treatment, 3.6±2.5 points after the first course of treatment and 3.4±2.5 points after the second course (p&gt;0.05). MRI results showed a decrease in disease activity by 83% after the first course of cladribine therapy and by 97.4% after the second course. No serious adverse events occurred in any of the patients.Conclusion. We demonstrated efficacy and safety of cladribine in real-life clinical practice in MS patients with frequent exacerbations and rapid disability progression (SPMS, RPMS, HAMS).

Role of PCSK9 Inhibitors in Venous Thromboembolism: Current Evidence and Unmet Clinical Needs.

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have recently emerged as promising therapeutic agents for lowering low-density lipoprotein cholesterol and reducing the risk of cardiovascular events. Moreover, preliminary evidence from randomized controlled trials (RCTs) suggests that PCSK9i may also offer beneficial effects for patients following venous thromboembolism (VTE), with the most significant reductions in risk appearing over time, particularly beyond the first year of treatment. However, there is a lack of randomized controlled data supporting their efficacy and safety in conjunction with standard anticoagulation therapy. This article aims to critically evaluate the existing evidence for the use of PCSK9i as a complementary therapy for VTE risk reduction, while also identifying unmet clinical and research needs and proposing potential strategies to address these knowledge gaps.

Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

7673 Genetic Analysis and Clinical Characterization of Patients with Congenital Hypopituitarism Due to Gene Defects

Abstract Disclosure: T.M. Sasson: None. I.J. Arnhold: None. B.B. Mendonca: None. L.R. Carvalho: None. Introduction: Congenital hypopituitarism is characterized by the deficiency of one or more hormones secreted by the anterior pituitary gland. The genetics of this pathology is complex, and the molecular diagnosis is established in approximately 13% of cases. Objectives: The aim of the present study is to characterize the phenotype harboring pathogenic variants causing congenital hypopituitarism. Methods: Among 393 subjects with congenital hypopituitarism followed up at a tertiary health center, 57 subjects (14,5%) were selected due to a confirmed molecular diagnosis by exome in 9 subjects or by gene panel or Sanger sequencing in 48 subjects. This was a retrospective study where data from medical records, clinical, laboratory and radiological characteristics were analyzed. Results: The most frequent variants identified by sequencing analyzes were in the following genes: PROP1 (29.8%), GH1 (22.8%), GHRHR (15.7%), followed by GLI2, OTX2, HESX1, POU1F1, TGIF1, GHRS, CDH2, SATB1, SOX3 e LZTR1. Consanguinity was reported in 50% of cases, and there was the presence of familial cases of short stature in 60%. The average age at the start of follow-up was 11.1 years (11 SD), 40% of them were male and 52.3% had physical stigmata typical of GH deficiency. Regarding hormonal deficiencies, 27 (47%) had isolated Growth Hormone Deficiency (DGHI) and the others, multiple deficiencies. MRI study of the pituitary gland showed some alteration in 66%, 54% of whom had adenohypophysis hypoplasia and 31% had an ectopic or non-visualized neurohypophysis. From 29 patients with IGF-1 levels available, 28 were below the reference range for sex and age. The serum GH peak after the stimulus test was on average 1.28 ng/mL (1.4SD), of these, only 4 cases had GH peak between 3.3 and 5.0 ng/mL and 1 patient with low IGF-1 and an ectopic neurohypophysis had GH peak of 6.0 ng/mL in a glucagon test. Regarding growth, the initial height in z-score was -4.8 and the average growth at the end of the first year of treatment was 10.7cm, with the average height after this period of Z-3.35. The average of final delta target height (final height Z-score minus the target height Z-score) of patients who underwent hormonal treatment was -0,53 (good response = delta &amp;lt;-1.5). Conclusion: In subjects with congenital hypopituitarism and an established molecular diagnosis, the most frequently affected genes were PROP1 and GH1, the great majority presented a stimulated GH peak &amp;lt; 3.3 ng/mL (only one patient had GH &amp;gt; 5), low basal serum IGF-1 and good increase in growth speed at the end of the first year of treatment with recovery of final height at the end of GH therapy. Presentation: 6/3/2024