Months Of Switching Research Articles

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

E054 Rituximab dose minimisation in rheumatoid arthritis, a retrospective outcome analysis

Abstract Background/Aims Rituximab was originally developed as a non-Hodgkin lymphoma treatment and rheumatology adopted the same dosing for rheumatoid arthritis(RA); two 1000mg doses two weeks apart for each maintenance cycle. UHSussex utilises self-referral for maintenance rituximab dosing once disease control lessens. Evidence demonstrates patients treated with lower dose rituximab still enjoy good disease control with less immunosuppression, reduced hospital attendance and reduction in drug expenditure. Following one two-dose cycle, stable RA patients were prescribed a single 1000mg dose from 2020 onwards. A retrospective outcome analysis was completed in August 2022; however, results were highly impacted by Covid-19 and a repeat analysis was required. Aim: to assess impact of a single 1000mg dose rituximab regime on patient sustained outcomes, dose intervals, Disease Activity Scores (DAS) and drug expenditure. Methods The pharmacy database was used to identify RA patients receiving rituximab from March 2020 to August 2023. Patients received at least one standard two-dose cycle before switching to a single infusion. Patients were excluded if lost to follow up (under care of rheumatology for less than a year following dose switching) or considered clinically unstable. Patient letters and departmental records were accessed for disease scores and treatment intervals. Results Table1: Results from the two analysis periods From the original cohort (31/59)53% remained on single dosing. Switch back tended to occur within 18 months of switching. DAS scores were not collected reliably and were omitted. Conclusion Covid-19 impacted services and attitudes during the initial study period. Many patients stopped treatment, particularly rituximab, due to the prolonged duration of effect, excluding them from analysis. The dose-interval increase during the first analysis was considered a result of the pandemic. Patients and clinicians delayed infusions; minimising immunosuppression due to perceived increased risk of Covid-19. The continued interval increase in the second analysis may identify a patient cohort in deep remission eligible for therapy review. The study highlights poor practice in collecting and recording DAS scores and appropriate patient-clinician interaction opportunities. 53% of patients remained on single infusions in August 2023 resulting in resource savings, reduced hospital attendance, immunosuppression and significant cost savings demonstrating the rationale for this option. Disclosure S. Butler: Honoraria; Abbvie, Janssen. H. Smith: Honoraria; Novartis, Abbvie.

1566. Determinants associated with weight gain among persons with HIV who switch to integrase strand transfer inhibitors (INSTI)

Abstract Background Weight gain associated with integrase strand transfer inhibitors (INSTI) has been well documented among patients with HIV. However, recent reports suggest that the observed weight gain among patients who switch to INSTIs may be associated in part with their pre-switch regimen. Methods We conducted retrospective analyses of a 50% sample of all treatment-experienced patients who switched to second-generation INSTI containing regimen (bictegravir/dolutegravir) at the Duke Adult Infectious Diseases Clinic (Durham, NC, USA) between 1 January 2014 and 31 December 2021. Covariates included sex at birth, age, race, ethnicity, pre-switch regimen, body mass index (BMI), CD4 count and HIV-1 viral load. All weights documented within 24 months from regimen switch were included. Outcomes of interest were percent change in weight and absolute weight change. Ordinary least squares was used to obtain average percent weight change from baseline, adjusted for covariates. Results Overall, 339 persons were included in the analyses. Cohort demographics were: median age 51.2 (interquartile range 44.4, 57.6), 73% male sex at birth, 56% Black, 4% Hispanic ethnicity. At regimen switch, median CD4 count was 671 (IQR 460-935), and 78% had a viral load &amp;lt; 200 copies/cc. Mean weight at regimen switch was 87.8 kg (standard deviation [SD] 22.1kg), and mean total weight change over 24 months post-switch was +1.3 kg (SD 7.1 kg). Overall, 28% of cohort members gained &amp;gt;5% of baseline body weight within 24 months of switch. Hispanic ethnicity (5.9% [95% CI 1.0, 10.7]) and BMI &amp;lt; 20 (3.7% [95% CI -0.3, 7.7]) were associated with post-switch weight gain. Only efavirenz-containing pre-switch regimens were significantly associated with weight gain over 24 months post-switch; EFV/FTC/TDF (3.1% [95% CI 0.2, 6.1]), all other EFV-containing regimens (6.3% [95% 0.1-12.4]). Conclusion Pre-switch regimens containing efavirenz were significantly associated with weight gain after switch to second-generation INSTI-based regimens, consistent with findings from non-US based cohorts. Disclosures Nwora Lance Okeke, MD MPH, Gilead Sciences: Advisor/Consultant

A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

Weight Gain After 12 Months of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV Patients.

Recent studies suggest that the introduction of antiretroviral agents such as integrase strand transfer inhibitors (INSTI) may lead to weight gain in people living with HIV (PLHIV). In this retrospective observational study, we report the weight changes observed in virologically suppressed HIV patients after 12 months of switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) due to a national change in public policy in Mexico. Patients on prior regimens based on TDF/FTC or ABC/3TC plus non-nucleoside retrotranscriptase inhibitor, INSTI, or protease inhibitor were included. In the 399 patients analyzed, a significant weight increase was found, as well as an increase in body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, and CD4+ cells after 12 months of switching treatment (all p ≤ .001). Mean weight gain was 1.63 kg [confidence interval (95% CI): 1.14-2.11], whereas the average percentage of weight gained was 2.5% (95% CI: 1.83-3.17). After considering the confounding effect of baseline weight status, the change in weight and BMI did not present significant differences between any of the prior treatment schemes. In conclusion, PLHIV switching to BIC/F/TAF therapy experienced weight gain after the first year of switching treatment. Although this weight gain could be due to the switch in treatment regimen, it cannot be excluded that it was caused by other factors since no comparable control group could be used for comparison.

Effectiveness of tumor necrosis factor inhibitors in children with enthesitis-related arthritis: a single-center retrospective analysis.

In children with enthesitis-related arthritis (ERA), the hip and sacroiliac joint function might be impaired if not properly treated. We sought to evaluate the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy using the inflammatory indicators, Juvenile Arthritis Disease Activity Score 27 (JADAS27) and magnetic resonance imaging (MRI). We conducted a single-center retrospective study of 134 patients with ERA. We evaluated the effect of anti-TNF therapy on the inflammatory indicators, active joint count, MRI quantitative score, and JADAS27 over 18 months. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) and the Hip Inflammation MRI Scoring System (HIMRISS) scoring systems for hip and sacroiliac joints scoring. The average age of onset of children with ERA was 11.62 ± 1.95 years, and they were treated with disease-modifying antirheumatic drugs (DMARDs) combined with biologics (n = 87, 64.93%). There were no differences in HLA-B27 positivity between the biologics and non-biologics treatment groups [66 (49.25%) vs. 68 (50.75%), P > 0.05]. Children who received anti-TNF (71 received etanercept, 13 adalimumab, 2 golimumab, and 1 infliximab) therapy improved significantly. Children with ERA used DMARDs and biologics at baseline (Group A) were followed up to 18 months, and their active joint count (4.29 ± 1.99 vs. 0.76 ± 1.33, P = 0.000), JADAS27 (13.70 ± 4.80 vs. 4.53 ± 4.52, P = 0.000) and MRI quantitative scores (P = 0.001) were significantly lower than those at baseline. Some of the patients (n = 13, 9.70%) were treated with DMARDs at the onset of the disease, but did not show significant improvement (Group B). After 6-18 months of switching to anti-TNF therapy, related indicators of the children were significantly lower than at baseline and 1 month (P < 0.013). At 18 months, a total of 33 patients (n = 74, 44.59%) in Group A and 7 (n = 13, 53.85%) in Group B reached inactive state. Eighteen months after diagnosis, anti-TNF therapy was found to be effective in children diagnosed with ERA. MRI is important for the early diagnosis of juvenile idiopathic arthritis. TNF-α inhibitors can significantly improve the clinical manifestations of sacroiliac joint and hip involvement in patients with ERA. Overall, the real-world study provides more evidence for precision diagnosis and treatment for other hospitals, families and patients.

Comparison of Intraoperative Neural Response Telemetry Results and Postoperative Neural Response Telemetry Results in Case of Children with Congenital Bilateral Severe to Profound Sensorineural Hearing Loss Undergoing Single Sided Cochlear Implantation.

This study is designed to compare the Intra Operative Neural Response Telemetry (NRT) results with Post-Operative NRT results of the cochlear implanted children, to assess the importance of Intra Operative NRT thresholds in device activation and/or switch on of the audio processor and to evaluate the importance of Intra and post operative AutoNRT results in predicting behavioural thresholds during mapping of prelingual Cochlear Implanted children. A total of thirty (30) children (16 boys, 14 girls) with congenital Bilateral (B/L) severe to profound Sensorineural hearing loss (SNHL) were included in this study. Children between the age range of 12 to 60 months were participated in this study. All the participants were implanted with Nucleus 24 cochlear implant system. In each patient, the intra operative NRT-thresholds were measured for all 22 active electrodes. Then Intra Operative NRT thresholds were correlated with Post-Operative NRT thresholds at the time of switch on and the behavioural map after six months of switch on of the device (Audio Processor). There is a significant enhancement observed in thresholds of postoperative NRT responses which were raised or absent during intraoperative session. There is a gain in NRT thresholds marked after 6 months of postoperative follow up in comparison with first measurement at the time of Switch On of the device but the change not that significant. During postoperative mapping, there was a significant positive correlation noticed between neural response telemetry level measurements and behavioural threshold level. Absent or elevated NRT responses during intraoperative testing for some electrodes especially basal electrodes does not mean that electrode is out of order or outside the cochlea, because an improvement in NRT thresholds usually occurs postoperatively. In case of children with congenital B/L severe to profound SNHL, the NRT values have a very useful role in predicting the behavioural thresholds. Combination of NRT values with behavioural thresholds and observations of Auditory Verbal Therapist can help in providing best suitable Map to the recipient. The online version contains supplementary material available at 10.1007/s12070-022-03284-x.

Changes in Body Mass Index Associated with Antiretroviral Regimen Switch Among Treatment-Experienced, Virologically Suppressed People Living with HIV in the United States

With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017. Multivariable linear regression was used to assess the association between regimen and mean changes in BMI at 6, 12, and 24 months after switch. In unadjusted analyses, BMI increases ranged from 0.30 kg/m2 (bDRV) to 0.83 kg/m2 (RPV) at 24 months following switch, but gains were observed with every regimen. In adjusted analyses, compared to DTG, only bDRV was associated with a smaller increase in BMI at all time points, while EVG/c and RAL were associated with smaller increases in BMI at 6 months only. Overall, results were consistent in analyses stratified by baseline BMI category. BMI increases were relatively small but followed an upward trend over time in this cohort of treatment-experienced, suppressed PLWH. Gains were attenuated with a longer period of follow-up. BMI gains did not differ by regimens, except for bDRV regimens, which were consistently associated with smaller BMI increases than DTG.

880-P: Insulin Regimen and Glycemic Control in People with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease with many patients requiring insulin treatment. Basal insulin (BI) is often added first followed by escalation to a multiple subcutaneous insulin injection (MSI) regimen. However, many patients with T2DM struggle managing the MSI regimen. As a result, their glycemic control remains poor after starting MSI. Our study investigates whether switching back to BI alone would improve glycemic control. Patients with T2DM and A1C ≥9.0% on MSI regimen seen in our clinic over two years were included in this analysis. Main study outcome was the A1C after ≥3 months of switching back to BI as compared to continuing MSI. We found 24 patients who were switched from MSI to BI and compared them with 58 patients who were continued on MSI (see Table). There were no significant differences at baseline between the two groups. On follow-up, the BI group had a mean change in A1C (%) of -1.6 ± 2.0 compared to -0.7 ± 1.5 in the MSI group. In addition, the daily dose of prescribed insulin on follow-up was lower in the BI group at 46 ± 14 units/day compared to 90 ± 70 units/day in the MSI group. Hypoglycemia rates were also lower in the BI group at 12% compared to 20% in the MSI group. We conclude that simplification of insulin regimen may improve A1C and decrease the risk of hypoglycemia in patients poorly controlled on MSI regimen. The improved glycemic control is likely related to improved adherence and lower risk of errors. Disclosure A. Arunachalam: None. R. Garg: None.

P549 Changing Lanes: Switching Therapies in Inflammatory Bowel Disease, An Observational Study

Abstract Background Switching between therapies in inflammatory bowel disease (IBD) is common and a paucity of data exists regarding the optimal switching strategy. A number of new drug therapies have recently emerged for the treatment of IBD. Failure of biologic and small molecule therapies occur regularly, prompting the need for a treatment switch. Our aim is to review trends amongst our patients who switched biologic/small molecule therapy to identify high risk characteristics and to look for predictor variables which may reduce the need to switch in the future. Methods This is a 4 year retrospective observational study of IBD patients who underwent a therapy switch. Patients were identified from a prospectively maintained IBD database of 141 patients. Patient demographics, treatment history, disease history, biomarkers (within 3 months of switch) and endoscopy results were reviewed. Minitab17 was used for statistical analysis. Results Switching of biologic therapy was observed in 39 patients (28%); 21 (54%) were male; mean age was 42.8Y. Of these, 21 (53.9%) had Crohn’s disease (CD), 17 (44%) had ulcerative colitis (UC) and 1 patient had indeterminate colitis. Mean disease duration at time of switch was 78 months. 82% (n=14/17) of UC patients had pancolitis. 43% (n=9/21) of CD patients had a previous intestinal resection. The most common initial therapy was Adalimumab 46% (n=18) (Fig1) with the most common switch to IFX 36% (n=14) (Fig2). Primary LOR occurred in 28% (n=11) and secondary LOR in 44% (n=17), the remainder switched due to infusion reaction/adverse effects (n=10) and clinical remission (n=1). Mean CRP was 13.68 (95% CI: 7.28, 20.09), mean FCP was 874 (95% CI: 418, 1329), mean mayo score was 1.88 (95% CI: 1.37, 2.39), mean SES CD score was 5.79 (95% CI: 3.24, 8.33). Median IFX level was 0.8ug/ml (IQR 0.4, 9.7), 37.5% (n=6/16) of the patients on IFX developed ADAs to IFX. Median Adalimumab level was 5.2ug/ml (IQR 1.4, 13.5) and 11% (n=2/18) developed ADAs to Adalimumab. A significant negative correlation was found between FCP and IFX level using Spearman rank correlation -0.822, p = 0.01. 39% (n=15) were on an immunomodulator, no significant association was found between immunomodulator therapy and primary/secondary LOR, p= 0.67 and p= 0.63. 28% (n=11) were admitted with an IBD flare in the 1st year post switch and 13% (n=5) underwent intestinal resection. 8 (21%) subsequently switched to a 3rd biologic agent. Conclusion The most common therapy switch was within Anti-TNF drug class, mean CRP and FCP were raised at the time of switch and a significant number of patients were admitted in the year post switch with an IBD flare. Pancolitis in UC and previous intestinal surgery in CD were common characteristics of those who switched.

White Matter Microstructure and Structural Networks in Treatment-Resistant Schizophrenia Patients After Commencing Clozapine Treatment: A Longitudinal Diffusion Imaging Study

Clozapine has a superior clinical effect in refractory schizophrenia, however its potential impact on white matter microstructure and neural networks is unclear. This study investigates such changes after 6 months of switching to clozapine in schizophrenia patients compared to controls, and whether any changes are related to clinical variables.

Switching to an Infliximab Biosimilar Was Safe and Effective in Dutch Sarcoidosis Patients.

The effect of switching from originator infliximab to biosimilar infliximab in patients with sarcoidosis is unknown. The objective of this study is to investigate the effect of switching from Remicade® or Inflectra® to Flixabi® in patients with severe refractory sarcoidosis. This single center retrospective cohort study was performed at St Antonius Hospital Nieuwegein, The Netherlands. All patients diagnosed with severe refractory sarcoidosis receiving Remicade® or Inflectra® switched to Flixabi®. The primary outcome was infliximab discontinuation within 6 months of switching. Secondary endpoints included adverse events and loss of clinical, functional, or inflammatory response. Out of 86 patients who switched to Flixabi®, 79 patients had complete data. None of the 79 patients discontinued infliximab during the first 6 months after switching. Five patients reported an adverse event related to Flixabi® treatment. We found no change from baseline in FVC, FEV1, DLCOc, 6MWT, and infliximab trough levels 26 weeks after switching. An improvement in physical functioning of 7.3 ± 13.4 points (p = 0.002) with RAND/SF36 and in biomarker sIL-2R (−475.58 ± 1452.39; p = 0.005) was observed. Switching from originator infliximab Remicade® or biosimilar infliximab Inflectra® to biosimilar infliximab Flixabi® did not result in treatment discontinuation or loss of clinical/functional/inflammatory remission.

White matter microstructure and structural networks in treatment-resistant schizophrenia patients after commencing clozapine treatment: A longitudinal diffusion imaging study

This study investigates changes on white matter microstructure and neural networks after 6 months of switching to clozapine in schizophrenia patients compared to controls, and whether any changes are related to clinical variables. T1 and diffusion-weighted MRI images were acquired at baseline before commencing clozapine and after 6 months of treatment for 22 patients with treatment-resistant schizophrenia and 23 controls. The Tract-based spatial statistics approach was used to compare changes over time between groups in fractional anisotropy (FA). Changes in structural network organisation weighted by FA and number of streamlines were assessed using graph theory. Patients displayed a significant reduction of FA over time (p<0.05) compared to controls in the genu and body of the corpus callosum and bilaterally in the anterior and superior corona radiata. There was no correlation between FA change in patients and changes in clinical variables or serum level of clozapine. There was no changes in structural network organisation between groups (F(7,280)=2.80;p = 0.187). This longitudinal study demonstrated progressive focal FA abnormalities in key anterior tracts, but preserved brain structural network organisation in patients. The FA reduction was independent of any clinical measures and may reflect progression of the underlying pathophysiology of this malignant form of schizophrenia illness.

Switching to fingolimod in PREFERMS: Effect of treatment history and naïvety on clinical, MRI and treatment satisfaction outcomes✰

BackgroundInjectable disease-modifying therapies (iDMTs) are often used as first-line treatments for relapsing multiple sclerosis. Fingolimod is frequently used following treatment with iDMTs. Whether prior iDMT treatment impacts the effectiveness of subsequent fingolimod therapy is unclear. Here, we assessed switching from iDMTs to fingolimod, and the impact of treatment history on fingolimod escalation using data from the 12-month ‘Prospective, Randomized, active-controlled, open-label study to Evaluate patient retention on Fingolimod versus approved first-line disease-modifying thErapies in adults with Relapsing–remitting Multiple Sclerosis’ (PREFERMS). The study design and results at the end of randomized treatment (EoRT) in PREFERMS have been published. MethodsBoth treatment-naïve patients and those who had previously received an iDMT were eligible for enrolment in PREFERMS, and one treatment switch was permitted on study. Pre-specified exploratory analyses compared outcomes in those randomized to fingolimod or to an iDMT at end of study (EoS), which included time spent on randomized and on switch treatment. Post hoc exploratory analyses (unadjusted for multiplicity owing to the large number of comparisons) among patients randomized to an iDMT who switched to fingolimod, compared outcomes longitudinally before (EoRT) and after (EoS) switching, and compared outcomes at EoRT and EoS among subgroups stratified by iDMT-treatment history. Outcomes included brain volume, various measures of gadolinium-enhancing [Gd+] lesion counts, annualized relapse rate (ARR), Symbol Digit Modalities Test (SDMT) score, patient-reported treatment satisfaction using the Medication Satisfaction Questionnaire (MSQ) and adverse event (AE) rates. ResultsAt EoS, 255 of 439 patients randomized to an iDMT had switched to fingolimod and 27 of 436 patients randomized to fingolimod had switched to an iDMT. By EoS, 44.2% of total treatment exposure in the iDMT group was to fingolimod and the mean time spent on fingolimod in this group was 220 days (approximately 7 months). Outcomes in the fingolimod group at EoS (brain volume, changes in Gd+ lesion counts, ARR, oral SDMT score and MSQ score) were similar to those seen at EoRT, but in the iDMT group these outcomes were more favorable at EoS than at EoRT and were similar to rates seen in the fingolimod group. Among patients who switched from iDMT to fingolimod, there were longitudinal improvements in ARR (EoRT, 0.3 [95% confidence interval (CI), 0.2–0.4]; EoS, 0.2 [0.1–0.3]; odds ratio, 0.5 [0.3–0.9]) and in treatment satisfaction (proportion of patients with MSQ > 5; EoRT, 67.4%; EoS, 90.4%; odds ratio, 5.7 [95% CI, 3.4–9.4]) after fingolimod treatment, and changes in brain volume, Gd+ lesion count, and AEs or AEs causing discontinuation were also more favorable at EoS than at EoRT. In all patient groups stratified by iDMT-treatment history, differences in outcomes narrowed or disappeared after fingolimod treatment. ConclusionThese analyses indicate that patients in PREFERMS had improved outcomes within months of switching to fingolimod from an iDMT and that improvements occurred irrespective of the number of iDMTs previously administered. These data provide a unique opportunity to explore clinical, radiological and safety outcomes associated with a range of clinically relevant treatment pathways.

Dose equivalency and efficacy of biosimilar erythropoietin stimulating agents: Data from real clinical practice.

Recently, biosimilar erythropoietin stimulating agents become available in Kazakhstan. Important properties of the biosimilar such as dose equivalency to the original medicine (originator) and the ability to maintain hemoglobin target levels remain insufficiently described in many clinical settings. Thus, the current study aims to determine dose equivalency and hemoglobin target levels in a cohort of dialysis patients who were switched from the originator to biosimilar. Retrospective data of 74 patients from different dialysis centers who received at least 6 months of originator and switched to biosimilar and had at least 6 months follow‐up were analyzed. The clinical data of 32 male and 42 female patients were collected. The mean age was 52.5 ± 13.5 years. There is no significant difference in mean levels of hemoglobin during pre‐switching from originator to biosimilar (6 months prior) and post switching period (9 months after). Additionally, a subgroup analysis of 59 patients who received originator (epoetin beta), 6 months before the switch, showed similar level of hemoglobin (110.7 ± 14 vs 113.2 ± 10 g/L, P = .05) 6 months after the switch to biosimilar (epoetin zeta) at the equivalent dose regimen (69.5 ± 29 vs 68.1 ± 30 IU/kg/wk, P = .55). However, after 9 months of switching, patients using lower doses of biosimilar (69.5 ± 29 vs 63.3 ± 30 IU/kg/wk, P < .01), showed significantly higher levels of hemoglobin (110.7 ± 14 vs 114.7 ± 8 g/L, P = .01) compared to preswitching period. In conclusion, long‐term use of lower doses of biosimilar managed to maintain hemoglobin within the target levels.

S170. PROGRESSIVE SUBCORTICAL VOLUME LOSS IN TREATMENT-RESISTANT SCHIZOPHRENIA PATIENTS AFTER COMMENCING CLOZAPINE TREATMENT

BackgroundThe association of antipsychotic medication with abnormal brain morphometry in schizophrenia remains uncertain. Early studies investigating a switch from first generation antipsychotic to clozapine have steadily shown a decrease of caudate volume over time; however nowadays most patients are already on second generation antipsychotic medications prior to clozapine commencement and it remains unclear whether switching to clozapine in such circumstances would have any such effect on the basal ganglia. In this study we aimed to comprehensively investigate whether after 6 months of switching to clozapine, subcortical structures demonstrate any progressively neuroanatomical changes in patients with treatment-resistant schizophrenia compared to healthy controls, and whether any such changes are related to clinical variables including treatment response and amount of clozapine taken.MethodsMRI images were acquired for all participants at baseline and after 6 months at University Hospital Galway in a 1.5 T scanner. The longitudinal pipeline of Freesurfer v.5.3.0, based on an unbiased within-subject anatomical template, was employed to segment eight subcortical regions-of-interest: lateral ventricle, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens. Subcortical volumes were bilaterally extracted following quality check of raw data and segmentation. Clinical assessments included the Positive and Negative Syndrome Scale (PANSS), The Scale for the Assessment of Positive Symptoms (SAPS), The Scale for the Assessment of Negative Symptoms (SANS) and Global Assessment Functioning Score (GAF). Two-way repeated ANCOVA was used to assess group differences in subcortical volumes over time and partial correlations to determine association with clinical variables. Change in volume was expressed using the following formula: (Follow Up -Baseline)/Baseline x 100.Results33 patients with treatment-resistant schizophrenia (TRS) and 31 healthy volunteers (HC) matched for sex and age were successfully recruited at both baseline prior to clozapine treatment and after 6 months. There was a significant effect of time on subcortical brain volumes between TRS and controls (F(7,143)= 52.54, p<0.001). Corrected post-hoc analyses demonstrated that patients had significant enlargement of lateral ventricles (F(1,59)= 48.89; p<0.001) and reduction of thalamus (F(1,59)= 34.85; p<0.001), caudate (F(1,59)= 59.35; p<0.001), putamen (F(1,59)= 87.20; p<0.001) and hippocampus (F(1,59)= 14.49; p<0.001) volumes. Thalamus and putamen volume reduction was associated with improvement in PANSS (r=0.42; p=0.021, r=0.39; p=0.033), SANS (r=0.36; p=0.049, r=0.40; p=0.027) and GAF (r=-0.39; p=0.038, r=-0.42; p=0.024). Reduced thalamic volume over time was associated with increased serum level at follow-up (r=-0.44; p=0.010). There was no significant overall effect of time on subcortical brain structures between patients responding to clozapine compared to patients non-responding to clozapine (F(7,20)=0.50; p=0.834).DiscussionThis study demonstrates that, despite the clinical and functional improvement of most patients with schizophrenia who are switched to clozapine, there is a counterintuitive progressive volume reduction in several subcortical structures over time. Furthermore, patients who have the greatest symptomatic improvement display the largest thalamo-putaminal reductions, indicating that volume reduction reflects an adaptive response associated with symptom improvement rather than a harmful or neurotoxic process in these patients.

EP15 Switching to biosimilar adalimumab: a real world study

Abstract Background Since the introduction of anti-TNF biosimilars in routine clinical practice, there has been a drive to implement the switch program for all biosimilars at the point of availability. Our Trust was aligned to NHS England strategy which required adoption of biosimilar within three months for new patients and one year for switchers. This could help deliver significant savings to the NHS whilst achieving similar clinical outcomes. We report our early experience of introducing adalimumab biosimilar (Imraldi®). Methods A list of all patients prescribed adlimumab was extracted through our database. A ‘switch’ letter was drafted and sent to all patients including Imraldi information sheet. Patients were given the opportunity to contact nurse helpline as needed. We reviewed all relevant records and collected data on any adverse events and disease outcome on either side of the switch. Results 198 patients were identified established on adalimumab. All had switched by October 2019 to Imraldi. Mean age of switchers was 48 (range 16-83 years). Gender distribution was equal (99 each). 35 (17%) were Asian, two Afro-Caribbean, four other and the remaining 157 (80%) were White Caucasian. 54 (27%) had RA, 81 (41%) PsA, 57 (29%) AS and six had JIA. Co-prescribed DMARDs included methotrexate (n = 53, 27%), sulfasalazine (n = 15, 7.5%), hydroxychloroquine (n = 14, 7%) and leflunomide in two individuals. 83 (42%) participants were prescribed adalimumab monotherapy. Prior to switch, median DAS28 for RA group was 2.28 (0.57 - 6.29). Median BASDAI and spinal VAS for AS cohort was 3.3 (0.8 - 8.8) and 3.0 (0 - 9) respectively. Tender and swollen joint components for PsARC were median three (0-8 tender, 0-6 swollen) in PsA group. Only 30% of the patients had been reviewed face-to-face following the switch. Their respective median disease activity indices were not significantly different from pre-switch assessments. Eleven patients had complained of adverse events including injection site reaction (n = 7) and loss of disease control (n = 6). Six of these decided against further biosimilar and requested to return to the originator. No obvious precipitating factors were identified. Conclusion Our experience of switching adalimumab patients has been reasonably successful. All were happy to switch after receiving a letter and having the opportunity to contact if necessary. Substantial annual cost savings of over £300,000 have been projected for this financial year. At group level there were no major differences in disease outcomes and 90% reported no issues. However, just under 10% of those reviewed have decided to return to the originator within three months of switch with loss of efficacy and thereby confidence in the drug. We support the routine switching from originator to biosimilar adalimumab however close monitoring is required certainly in the first few weeks of dose administration. Disclosures J. Begum None. M.K. Nisar None.

Bisoprolol transdermal patch improves orthostatic hypotension in patients with chronic heart failure and hypertension

ABSTRACT β blockers (BBs) play an important role in heart failure (HF) treatment. However, orthostatic hypotension (OH) is sometimes caused by BBs. The bisoprolol transdermal patch works more slowly and is long acting compared with the bisoprolol fumarate tablet. The risk of OH may be reduced by using the bisoprolol transdermal patch. We evaluated 57 consecutive patients who were taking the bisoprolol fumarate tablet for chronic HF with hypertension from November 2016 to September 2017. We switched the patients to the bisoprolol transdermal patch. Because 12 of 57 subjects could not continue using the bisoprolol transdermal patch, we analyzed the remaining 45 patients. We investigated BP, blood tests, and changes in BP from supine to standing positions before and after 6 months of switching from tablet to patch. OH was diagnosed by observing a systolic/diastolic BP drop of at least 20/10 mmHg or an absolute systolic BP (sBP) of <90 mmHg from the standing position. No significant changes were observed in the BP and BPs from supine to standing positions, whereas log brain natriuretic peptide was significantly reduced after switching from patch to tablet (2.102 to 2.070pg/dl, P = .039). OH, which occurred in originally 17 patients, showed improvement and eventually appeared in 4 patients. In these patients, changes in BP from supine to standing positions were also significantly improved (changes in sBP, −11 to −6mmHg, P = .016). This study demonstrated that switching from the bisoprolol fumarate tablet to transdermal patch reduced the morbidity of OH in HF patients.

P620 Maintenance of clinical remission with SB5 biosimilar after switch from adalimumab originator: Real-life experience of a tertiary referral centre

Abstract Background Adalimumab (ADM) biosimilars have been demonstrated as safe and effective as the ‘originator’ in trials for other autoimmune disorders, but real-life evidence in inflammatory bowel diseases (IBD) is lacking. The aim of the study was to demonstrate maintenance of clinical remission (CR) after switch from ADM ‘originator’ to biosimilar SB5. Methods Data were retrospectively collected from November 2018 to September 2019. All IBD patients in CR after at least 6 months of ‘originator’ and switched to SB5 were included. The primary outcomes were maintenance of CR at 6 months after switch (defined as Partial Mayo Score 0–1 for ulcerative colitis and Harvey–Bradshaw Index ≤4 for Crohn’s disease) and overall comparable safety. A historical cohort of patients treated only with the ‘originator’ was included for comparison, using a Cox regression model with a time-varying covariate. Results In total, 96 patients were included. Baseline characteristics of the cohort are reported in Table 1. Maintenance of CR after 6 months of switch was reported in 89/96 (92.7%) patients. Levels of C-reactive protein (CRP) significantly increased over time from baseline to 6 months (from 2.67 ± 2.61 to 4.98 ± 5.81 mg/dl, p = 0.03), but no difference between the two time points was found when considering a relevant flare only for CRP above the lab cut-off (5 mg/dl). A comparison of CR persistence over time between ‘originator’ cohort and SB5 ‘switching’ cohort did not show any statistical difference (Hazard Ratio 1.07, 95% CI 0.57 – 2.01). With regard to adverse events, SB5 showed an overall safety profile, with only 2/96 (2.1%) patients interrupting the treatment due to anti-TNF-induced psoriasis. In 42/96 (43.8%) of patients, at least one injection site reaction was reported; only in one case a re-switch to ‘originator’ was needed for local intolerance. Conclusion SB5 is safe and effective in maintaining CR after switching from the ‘originator’. Injection site reaction is a frequent but usually manageable side effect. Larger multi-centre cohort and endoscopic assessment are needed to confirm the initial findings.

Evaluating Efficacy, Safety, and Pharmacokinetics After Switching From Infliximab Originator to Biosimilar CT-P13: Experience From a Large Tertiary Referral Center.

The use of infliximab biosimilar CT-P13 has increased in patients with inflammatory bowel disease. Nevertheless, doubts about switching from infliximab originator to biosimilar still exist among patients and health care professionals. Our tertiary referral center underwent a mandatory switch from infliximab originator to CT-P13 in 2017. We investigated pharmacokinetics, efficacy, and safety of this switch. The primary endpoint was infliximab discontinuation within 6 months of switching. Secondary endpoints included loss of clinical remission, need for treatment optimization, adverse events, evolution of patient-reported outcome, C-reactive protein, infliximab trough levels, and antidrug-antibodies. A total of 361 patients (54.0% male, 70.0% Crohn's disease, 55.6% in clinical remission) were enrolled. Infliximab discontinuation within 6 months was observed in 4%. Loss of clinical remission, adverse events, and antidrug-antibodies were identified in only 2.0%, 2.2%, and 1.1% of patients, respectively. C-reactive protein concentrations and infliximab trough levels remained stable. Independent factors associated with remission at 6 months were lower PRO2 at switch (HR 6.024; 95% CI, 4.878-8.000; P < 0.0001) and higher hemoglobin levels (HR 1.383; 95% CI, 1.044-2.299; P = 0.018). Switching from infliximab originator to CT-P13 was not associated with an increased risk of treatment discontinuation, loss of clinical remission, or adverse events. No significant changes in infliximab trough levels or immunogenicity could be identified.