082 Real world experience of treating multiple sclerosis with alemtuzumab

2018 ◽  
Vol 89 (6) ◽  
pp. A33.2-A33 ◽  
Author(s):  
Ellie Khalili ◽  
Brent Venning ◽  
Mike Boggild ◽  
Simon A Broadley
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Real World ◽  
Median Number ◽  
Trial Data ◽  
Effective Therapy ◽  
Phase Iii ◽  
Phase 3 ◽  
Randomised Controlled

IntroductionAlemtuzumab is a highly effective therapy for multiple sclerosis that has a significant, but well-defined adverse event profile. We report cases treated since the commercial release of alemtuzumab at two centres in Queensland with the aim of comparing real-world experience with trial data.MethodsThis was a retrospective case note review of patients treated with alemtuzumab for multiple sclerosis since becoming commercially available in Australia. The two sites were the Gold Coast University Hospital and the Townsville Hospital. Demographic, clinical and MRI data were systematically collected from the available records at each site. De-identified aggregated data were analysed using descriptive statistics (mean (±SD), median (range)) and compared with phase III clinical trial data.Results104 cases treated with alemtuzumab were identified at the two sites. The median age at first treatment was 3817–55 years, slightly older than the trial populations (33 and 35 years) and two-thirds were female. The mean disease duration was 8.4 (±7.0) years, which is longer that seen in the trials (2.1 and 4.5 years). The median number of prior relapses was 31–12 with 1 (0–3) in the prior 2 years. The median number of prior treatments for MS was 1.5. The median follow up was 201–35 months. The median EDSS at time of first treatment was 2 (0–7) and at last follow up was 1.5 (0–7). At last follow up, 24/104 (23%) had improved, 61/104 (58%) were stable and 9/104 (9%) had worsened. Autoimmune adverse events were seen in 18/104 (17%) with autoimmune thyroid disease being the most common (13/104 (13%).ConclusionAlemtuzumab is an effective therapy for MS. Clinical outcomes in a real world setting were similar to those seen in phase III clinical trials. Autoimmune diseases occurred in a similar proportion to those seen in clinical trials.References. Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: A randomised controlled phase 3 trial. Lancet2012;380(9856):1819–28.. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: A randomised controlled phase 3 trial. Lancet2012;380(9856):1829–39.

scholarly journals Ocrelizumab in Multiple Sclerosis: A Real-World Study From Spain

2021 ◽  
Vol 11 ◽  
Author(s):  
Angel P. Sempere ◽  
Leticia Berenguer-Ruiz ◽  
Ines Borrego-Soriano ◽  
Amparo Burgos-San Jose ◽  
Luis Concepcion-Aramendia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Real World ◽  
Median Number ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Clinical Practice Setting ◽  
Number Of Treatment ◽  
Relapsing Multiple Sclerosis

Objectives: The aim of this study was to describe the tolerability, safety, and effectiveness of ocrelizumab for primary progressive multiple sclerosis (PPMS) and relapsing multiple sclerosis (RMS) in a clinical practice setting.Methods: In this retrospective observational study, we analyzed clinical and MRI data in all patients with PPMS and RMS who had received at least one infusion of ocrelizumab in two health areas in south-eastern Spain. Patients involved in any ocrelizumab trial and those patients with a follow-up shorter than 6 months were excluded.Results: The cohort included 70 patients (42 women) who had received ocrelizumab; 30% had PPMS and 70%, RMS. At baseline, patients' mean age was 47.1 years in the PPMS group and 39.2 years in the RMS group, while the median EDSS was 3.0 and 2.5, respectively. Median follow-up was 13.6 months. The median number of treatment cycles was three. Most patients remained free from clinical and MRI activity after ocrelizumab initiation. Baseline MRI showed T1 Gd-enhancing lesions in 57% of the patients; by the first MRI control at 4–6 months, all patients except one were free of T1 Gd-enhancing lesions (69/70, 98.6% P < 0.001). The proportion of patients with NEDA was 94% in the group of RMS patients who were followed for at least 1 year. Ocrelizumab was generally well-tolerated; the most common adverse events were infusion-related reactions and infections, none of which were serious.Conclusions: Our real-world study supports the tolerability, safety, and effectiveness of ocrelizumab in clinical practice.

Real-world survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) treated with abiraterone acetate (Abi) or docetaxel (Doc) and comparison with clinical trial outcomes.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 53-53
Author(s):  
Daniel M. Geynisman ◽  
Andres F Correa ◽  
Chethan Ramamurthy ◽  
J Robert Beck ◽  
Elizabeth A. Handorf
Keyword(s):  
Clinical Trial ◽  
Observational Study ◽  
Real World ◽  
Trial Data ◽  
Phase Iii ◽  
Real World Data ◽  
Large Variability ◽  
World Data ◽  
Level Data

53 Background: Multiple phase III trials have proven that Abi and Doc both improve overall survival (OS) in men with mHSPC. No randomized trials have compared the two approaches. Methods: We conducted a retrospective, observational study to compare OS in de novo M1 men, treated with Abi vs. Doc using patient-level data from the Flatiron health EHR-derived de-identified database. We also compared this real-world OS to trial level data using extracted data points along the OS curves from CHAARTED and LATITUDE trials. OS was compared via Kaplan-Meier curves. Analyses were adjusted via propensity score weighting for age, Gleason score, PSA at diagnosis, race, ethnicity, ECOG PS, insurance type and treatment setting. Results: The cohort included 418 Abi pts and 807 Doc pts (Table). Median follow-up was 13.5 mo for Abi and 31.6 mo for Doc. Unadjusted median OS for Abi and Doc were 31.6 mo (95% CI 28.1-NA) and 41.8 mo (95% CI 37.4-46.3) respectively (P=0.09). Twelve mo and 24 mo OS for Abi was 86.3% and 69%; for Doc it was 89.8% and 72.1 %. Median adjusted OS for Abi and Doc were 31.6 mo (95% CI 28.0-undefined) and 38.8 mo (95% CI 33.1-46.3) respectively (P=0.4). Twelve mo and 24 mo adjusted OS for Abi was 86.6% and 69.4%; for Doc it was 87.9% and 69.2%. Based on extracted trial data, in LATITUDE, Abi treated pts had 12 mo and 24 mo OS of 93.5% and 77.0%; in CHAARTED, Doc treated pts had 12 mo and 24 mo OS of 94.3% and 83.6%. Conclusions: Utilizing real-world data, we demonstrate that 12 and 24-months OS are clinically and statistically similar between Abi and Doc in men with mHSPC. Median OS is also similar, although due to limited follow-up, the estimate of median OS for Abi has large variability. In addition, we show that clinical trial pts had superior outcomes to those in a real-world clinic population. Recent meta-analyses of trial data have not found significant differences in OS for Abi vs. Doc; this analysis of real-world data confirms these findings and indicates that they may be generalizable to a broader patient population. Although this observational study is subject to residual confounding and missing data, it provides further evidence to support the use of both Abi and Doc in men with mHSPC. Differentiating costs, side-effects and QOL can thus become more prominent when making decisions about therapy. [Table: see text]

scholarly journals Real-world experience of ocrelizumab in multiple sclerosis patients in Latin America

2021 ◽  
Vol 79 (4) ◽  
pp. 305-309
Author(s):  
Juan Ignacio ROJAS ◽  
Liliana PATRUCCO ◽  
Manuel FRUNS ◽  
Giesela HORNUNG ◽  
José FLORES ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Latin America ◽  
Real World ◽  
Phase Iii ◽  
Imaging Results ◽  
Relapsing Remitting ◽  
Patient Profiles ◽  
The Mean ◽  
Multiple Sclerosis Patients

ABSTRACT Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles. Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America. Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging. Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days. Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.

scholarly journals Effect of empagliflozin on albuminuria, eGFR and serum creatinine: updated results from the ABCD nationwide empagliflozin audit

2021 ◽  
Author(s):  
Thomas SJ Crabtree ◽  
Alex Bickerton ◽  
Jackie Elliott ◽  
Rajeev Raghavan ◽  
Dennis Barnes ◽  
...  
Keyword(s):  
Real World ◽  
Estimated Glomerular Filtration Rate ◽  
Haemodynamic Effects ◽  
Phase Iii ◽  
Clinical Endpoints ◽  
Urine Albumin ◽  
Signed Rank ◽  
Randomised Controlled ◽  
End Stage

Introduction: Evidence from phase III and the EMPA-REG OUTCOME trials have demonstrated improvements in renal endpoints with empagliflozin use. The EMPA-KIDNEY trial is currently underway and is assessing whether there are benefits of empagliflozin in improving renal outcomes in people both with and without diabetes, and the mechanism has been suggested to be similar to that of ACE inhibitors with the haemodynamic effects of sodium-glucose co-transporter-2 inhibition reducing intraglomerular pressure.Aim: To assess the impacts of empagliflozin use on albuminuria and estimated glomerular filtration rate (eGFR) in a real-world UK-based audit.Methods: Data were collated via the ABCD nationwide audit programme, with analyses performed using either t-tests/ ANOVA or Wilcoxon signed rank/Kruskal–Wallis tests. Pre-specified stratified subgroup analyses by baseline eGFR and baseline albuminuria levels were also performed.Results: Our results demonstrated significant reductions in albuminuria across the population as a whole. When stratified by baseline albuminuria levels, those with microalbuminuria (30–300 μg/mg) or macroalbuminuria (>300 μg/mg) had significant improvements in urine albumin levels at 6-month (3–9-month) follow-up, with median changes of −17.7 μg/mg (p<0.0001; 95% CI −17.4 to −23.7) and 379.4 μg/mg (p=0.03; 95% CI −269.9 to −725.4), respectively. Across the population as a whole, eGFR reduced initially (at 6 months, −1.26 mL/min/1.73 m3; p<0.0001; 95% CI −0.87 to −1.64) before recovering to baseline by 24 months. When stratified by baseline eGFR, those with reduced renal function (eGFR <90) recovered quickest, with improvements in eGFR noted from baseline by 24 months.Conclusion: In this real-world analysis, the results are comparable to those in randomised controlled trials and are likely more generalisable to UK clinical practice. Unfortunately, we do not have clinical endpoints such as end-stage renal failure, renal death or dialysis as part of our dataset. Future audits could consider including these data to establish clinical as well as biochemical outcomes.

scholarly journals Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection

2020 ◽  
Vol 10 (1) ◽  
pp. 2
Author(s):  
Rosa Escudero-Sánchez ◽  
María Ruíz-Ruizgómez ◽  
Jorge Fernández-Fradejas ◽  
Sergio García Fernández ◽  
María Olmedo Samperio ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Recurrence Rates ◽  
Factors Associated ◽  
Clostridioides Difficile ◽  
Multicentre Cohort Study ◽  
Clostridioides Difficile Infection ◽  
Prevention Of Recurrence ◽  
Multicentre Cohort

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

scholarly journals Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

2021 ◽  
pp. 135245852110002
Author(s):  
Bruce AC Cree ◽  
Jeffrey A Cohen ◽  
Anthony T Reder ◽  
Davorka Tomic ◽  
Diego Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Therapeutic Benefit ◽  
Disease Modifying Therapies ◽  
Long Term Follow Up ◽  
Post Hoc ◽  
Switch Group ◽  
Relevant Outcome

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI). Objective and Methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5–1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo. Results: At 8 years’ follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%–43.1%) of assessed participants in the IFNβ-1a–fingolimod switch group and 41.9% (36.6%–47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a–fingolimod switch group than on continuous fingolimod (5.4% [3.0%–9.5%] vs 14.2% [10.8%–18.4%], p = 0.01). Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

scholarly journals Efficacy and Safety of Teriflunomide in Multiple Sclerosis across Age Groups: Analysis from Pooled Pivotal and Real-world Studies

2021 ◽  
Vol 13 ◽  
pp. 117957352110287
Author(s):  
Jiwon Oh ◽  
Sandra Vukusic ◽  
Klaus Tiel-Wilck ◽  
Jihad Said Inshasi ◽  
David Rog ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Real World ◽  
Age Groups ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Additional Group ◽  
Disability Status ◽  
Scale Scores ◽  
Post Hoc ◽  
Phase Ii And Iii

Background: Evidence suggests that efficacy and safety of disease-modifying treatments for multiple sclerosis may differ with age. We evaluate efficacy and safety of teriflunomide across age subgroups of patients from pooled clinical trials and real-world studies. Methods: Post hoc analyses of patients who received teriflunomide 14 mg in the pooled phase II and III TEMSO, TOWER, TENERE, and TOPIC core and extension studies (n = 1978), and the real-world Teri-PRO (n = 928) and TAURUS-MS I (n = 1126) studies were conducted. Data were stratified by age at study entry: ⩽25, >25 to ⩽35, >35 to ⩽45, and >45 years. In Teri-PRO and TAURUS-MS I, an additional group, >55 years, was assessed. Results: In the pooled core studies, teriflunomide reduced annualized relapse rate (ARR) versus placebo across all ages. Unadjusted ARRs remained low across age groups in pooled extensions (0.18-0.30), Teri-PRO (0.10-0.35), and TAURUS-MS I (0.14-0.35). Baseline Expanded Disability Status Scale scores were higher with age, but stable through core and extension studies (mean increases over 7 years: ⩽25 years, +0.59; >25 to ⩽35 years, +0.46; >35 to ⩽45 years, +0.35; >45 years, +0.81). Across age groups, adverse event (AE) incidences were 78.4% to 90.7% in pooled core and extension studies and Teri-PRO, and 29.2% to 37.7% in TAURUS-MS I; serious AE incidences were ⩽21.3% in all studies. In pooled phase III and Teri-PRO studies, lymphocyte count decreases over 1 year after initiating teriflunomide, and proportions of patients developing lymphopenia, were small across age groups. Conclusions: Teriflunomide efficacy was demonstrated regardless of age. Safety was generally consistent across age groups.

scholarly journals Long Term Real-World Outcomes of Trifluridine/Tipiracil in Metastatic Colorectal Cancer—A Single UK Centre Experience

2021 ◽  
Vol 28 (3) ◽  
pp. 2260-2269
Author(s):  
Daniel Tong ◽  
Lei Wang ◽  
Jeewaka Mendis ◽  
Sharadah Essapen
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Median Number ◽  
Current Data ◽  
Real World Data

In the UK, Trifluridine-tipiracil (Lonsurf) is used to treat metastatic colorectal cancer in the third-line setting, after prior exposure to fluoropyrimidine-based regimes. Current data on the real-world use of Lonsurf lack long-term follow-up data. A retrospective evaluation of patients receiving Lonsurf at our Cancer Centre in 2016–2017 was performed, all with a minimum of two-year follow-up. Fifty-six patients were included in the review. The median number of cycles of Lonsurf administered was 3. Median follow-up was 6.0 months, with all patients deceased at the time of analysis. Median progression-free survival (PFS) was 3.2 months, and overall survival (OS) was 5.8 months. The median interval from Lonsurf discontinuation to death was two months, but seven patients received further systemic treatment and median OS gained was 12 months. Lonsurf offered a slightly better PFS but inferior OS to that of the RECOURSE trial, with PFS similar to real-world data previously presented. Interestingly, 12.5% had a PFS > 9 months, and this cohort had primarily left-sided and RAS wild-type disease. A subset received further systemic treatment on Lonsurf discontinuation with good additional OS benefit. Lonsurf may alter the course of disease for a subset of patients, and further treatment on progression can be considered in carefully selected patients.

Impact of PSMA PET/CT on SRT planning: Preliminary results from the randomized phase III trial NCT03582774.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 30-30
Author(s):  
Jeremie Calais ◽  
Wesley R Armstrong ◽  
Amar Upadhyaya Kishan ◽  
Kiara M Booker ◽  
David Elashoff ◽  
...  
Keyword(s):  
Success Rate ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Preliminary Results ◽  
Volume Delineation ◽  
Psma Pet ◽  
Pet Ct ◽  
The Impact

30 Background: The purpose of this trial is to evaluate the success rate of salvage radiation therapy (SRT) for recurrence of prostate cancer (PCa) after radical prostatectomy with and without planning based on prostate specific membrane antigen (PSMA) positron emission tomography (PET). Methods: This is a multicenter, prospective, randomized, controlled, open-label, Phase 3 clinical imaging trial powered for clinical outcome at 5 years. UCLA is the leading central site in which PSMA PET, clinical follow-up and data management are being done. UCSF was a participating site in which PSMA PET imaging can be done. SRT can be performed anywhere, patients are followed remotely by the UCLA investigators. Patients scheduled for SRT for recurrence after primary prostatectomy and with PSA ≥ 0.1ng/ml at time of enrollment were eligible. Patients were randomized to proceed with standard SRT allowing for any conventional imaging aside from PSMA PET/CT (control arm) or undergo a 68Ga-PSMA-11 PET/CT scan prior to SRT planning (investigational arm). The primary endpoint is the success rate of SRT at 5 years in patients who undergo SRT. We report here the preliminary results of a secondary endpoint: the impact of PSMA PET on SRT planning by comparing the pre-randomization RT plans prospectively obtained on surveys before randomization to the actually delivered RT plans obtained after follow-up. Results: Enrollment of the trial was complete. 193 patients were enrolled from 09.06.2018 to 08.17.2020. 7/90 patients (9%) in the control arm dropped-out the study because they underwent a PSMA PET at another institution, while 1/103 (1%) patients of the intervention arm dropped-out due to COVID-19 related complications. After a median follow-up of 13.3 months (last follow-up date 09/01/2020), delivered RT plans were obtained in 60/83 (72%) and 70/102 (69%) of patients of the control and the PSMA arms, respectively. Median PSA at enrollment was 0.32 ng/ml (IQR 0.17-1.35) and 0.22 ng/ml (IQR 0.14-0.50) in the control and PSMA arms, respectively. There was a change between the intended pre-randomization RT plan and the actually delivered RT plan in 17/60 (28%) and 40/70 (57%) of the patients in the control and PSMA arms, respectively (p = 0.002). SRT was aborted in favor of systemic therapy and/or metastasis directed RT for extra-pelvic M1 disease in 2/60 (3%) and 12/70 (17%) of the control and PSMA arms, respectively (p = 0.17). Dose prescription and/or target volume delineation was changed in 2/60 (3%) and 1/70 (26%) in the control and PSMA arms, respectively (p = 0.001). Conclusions: In this prospective randomized phase 3 study, PSMA PET had an impact on the SRT plan in more than half of the patients. Long-term follow-up will show if the impact of PSMA PET on SRT planning translates into improved outcome or not. Clinical trial information: NCT03582774.

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