Cause Of Switching Research Articles

Treatment pattern among patients with relapsed/refractory multiple myeloma (RRMM) who had received pomalidomide-based regimens in Taiwan

ABSTRACT Background/purpose The treatment landscape of relapsed/refractory multiple myeloma (RRMM) is rapidly evolving in Taiwan. The present study aimed to assess the treatment patterns among RRMM patients in Taiwan. Methods This retrospective, chart review-based, non-interventional study collected data on RRMM patients (≥20 years old) receiving pomalidomide-based treatment between January 2017 and December 2020 across five sites in Taiwan. Results Median age of the study population was 65.6 years. Approximately 75% patients received a doublet regimen and 25% were on a triplet regimen. Disease progression was the most common cause for switching to pomalidomide-based treatments in doublet (71.2%) and triplet (58.3%) groups. Patients in doublet and triplet groups (>80%) received 4 mg pomalidomide as a starting dose. Overall response rate (ORR: 31.5% and 45.8%) and median progression-free survival (PFS: 4.7 and 6.8 months) were reported in the doublet and triplet regimen. Doublet regimen was discontinued mainly due to disease progression or death (78.1%); however, triplet regimen patients mainly terminated their treatment due to reimbursement limitations (29.2%). Healthcare resource utilization (HRU) was comparable between doublet and triplet groups. Conclusion In Taiwan, half of RRMM patients received pomalidomide-based triplet regimens. Triplet regimens showed a trend towards better outcomes with longer PFS and higher response rates compared to doublets. Notably, the duration of triplet use is influenced by reimbursement limitations. This study provides insight into RRMM treatment patterns in Taiwan and the findings suggest that triplet regimens may be a better alternative than doublet regimens.

Real-world evidence of switching P2Y12 receptor–inhibiting therapies to prasugrel after PCI in patients with ACS: results from EFF-K registry

BackgroundPotent P2Y12 inhibitors are recommended for up to 12 months after percutaneous coronary intervention (PCI) in patients diagnosed with acute coronary syndrome (ACS). However, the prescription pattern is diverse in real world practice, which includes various switching between antiplatelet regimens. In this study, we analyzed the prescription patterns of prasugrel, and assessed the safety and effectiveness of P2Y12 inhibitors switching patterns in a real world registry of patients subjected to PCI after ACS.MethodsThe EFF-K study included 3077 ACS patients receiving prasugrel-based dual antiplatelet therapy. The cohort was divided into those who were administered with prasugrel as the primary antiplatelet treatment (naïve cohort) or as a substitute agent after clopidogrel or ticagrelor pre-treatment (switch cohort). The primary endpoint was a net adverse clinical event (NACE; a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or TIMI major bleeding unrelated to coronary-artery bypass grafting).ResultsA total of 3077 patients diagnosed with ACS were included in the analysis. Among the total population, 726 patients (23.6%) were classed as the naïve cohort and 2351 patients (76.4%) as the switch cohort. Baseline characteristics showed that the switch cohort had more comorbidities, such as hypertension, diabetes mellitus, heart failure and previous PCI. The major cause of switching to prasugrel in the switch cohort was the necessity for a more potent antiplatelet agent (56.3%). During a 12-month follow-up period, 51 patients (1.7%) experienced at least one NACE. The incidence of NACE did not differ between the naïve and switch cohort (1.5% vs. 1.7%, Hazard ratio 1.17, 95% Confidence interval 0.56–2.43, P = 0.677). In subgroup analysis, no significant interaction was observed between the treatment strategy and the incidence of NACE across various subgroups.ConclusionsDual antiplatelet therapy with prasugrel seems to be safe and effective both as a primary treatment and as a substitute for other P2Y12 inhibitors in a real world registry of Asian ACS patients receiving PCI.Trial registration: KCT0002356, registered June 13, 2017.

A non-synonymous SNP in homolog of BADH2 gene is associated with fresh pod fragrance in dolichos bean (Lablab purpureus var. lignosus (Prain) Kumari).

Fresh pods are harvestable and marketable economic product in dolichos bean. Fresh pod fragrance is one of the 'farmers' and 'consumers' preferred traits in dolichos bean varieties. The pods with high fragrance fetch a premium price in the market. In breeding programmes, pod fragrance is routinely assessed by organoleptic (sensory) means, which is highly relative and subjective. Identification of linked DNA markers not only offer an objective means but also enable selection of fragment genotypes at seedling stage itself. Betaine aldehyde dehydrogenase (BADH) is known to be the key gene responsible for fragrance in other legumes such as vegetable soybean and mung bean. Taking cues from highly conserved domains in proteins coded by BADH genes, we isolated dolichos bean homolog (LpBADH2) of soybean GmBADH2 gene using reported degenerate primers designed to conserved domains. Analysis of the translated amino acid sequence of LpBADH2 showed high degree of similarity (97.30%) with those of soybean homolog (GmBADH2). Conserved amino acid sequence of aldehyde dehydrogenase-super family were also identified in LpBADH2. Multiple sequence alignment of nucleotide sequences of LpBADH2 with those of related legumes using "ClustalW" revealed the presence of a single non-synonymous single nucleotide polymorphic (SNPs) and three synonymous SNP sites in LpBADH2. The substitution of the amino acid tyrosine in (fragrant genotypes) with phenyl alanine (non-fragrant genotypes) in protein coded by LpBADH2 appeared to be the cause for switch over from fragrance to non-fragrance in dolichos bean. These results are discussed in relation to strategies to breed dolichos bean cultivars with desired level of pod fragrance.

HIV/AIDS patients' knowledge, attitude, and practice toward anti-retroviral therapy medications' adverse effects and associated factors in Tikur Anbessa Specialized Hospital.

Adverse effects (AEs) have been reported with all antiretroviral therapy (ART) medications, and it was among the most common cause for switching or terminating therapy and drug non-adherence. Even though AEs of ART medications are common and to be expected, little study has been conducted on the understanding of patients on the AEs. Therefore, this study aimed to assess patients' knowledge, attitude, and practice (KAP) toward ART medications' AEs and associated factors. A cross-sectional study design was applied using an interviewer-administered questionnaire from June to September 2021 on human immunodeficiency virus/acquired immunodeficiency syndrome patients on follow-up at Tikur Anbessa Specialized Hospital, Ethiopia. Data was gathered, cleaned, and analyzed using SPSS version 23. Logistic regression analysis was performed to assess the relationship between the independent variable and patients' knowledge and attitude about the AEs of ART medication. A p-value of 0.05 was used to determine the statistical significance. About 230 people were enrolled in this study, with 51.3% of them female. Study participants had a mean age of 36 years (standard deviation = 14.19). Of 230 participants, 67.8% had received advice on the AEs of ART medications. Poor knowledge and attitude were observed among 47.8 and 51.3% of respondents, respectively. Prior AEs experience, lack of experiencing opportunistic infection, and lack of counseling about ART medications' AEs were associated with poor knowledge, whereas female gender and a lack of counseling regarding ART medications' AEs were associated with a negative attitude (p < 0.05). Even though most patients (81.7%) report AEs of the medication to professionals, a significant number of patients involved in malpractices such as taking other drugs to treat AEs (24.3%), not prepared to do anything (27.1%), change the suspected drug (24.3%), reduce the dose (18.7%), and use local herbal medicines to treat suspected AEs (20.2%). Overall, the study participants had poor knowledge, lack of positive attitudes, and non-adherence to the actual recommended practice toward AEs of ART medications. Lack of comorbidity, having prior AEs experience, and lack of counseling regarding ART medication AEs were associated with poor knowledge. Female gender and a lack of counseling on the AEs of ART medications were associated with a negative attitude.

Overview of peritoneal dialysis outcomes in Northern Cyprus: a nation based study

Aim: Peritoneal dialysis (PD) is the more preferred renal replacement therapy (RRT) option for most patients with end-stage renal disease (ESRD) who can not achieve a kidney transplantation. By an enhanced national PD program, more patients may have a chance to take the advantage of this treatment option. In this study, we aim to investigate whether PD is preferred as the first dialysis treatment modality in Northern Cyprus and reveal the outcomes in order to improve the further PD program. &#x0D; Material and Method: Peritoneal dialysis patients aged above 18 years who were followed between 2003-2021 in Northern Cyprus were investigated retrospectively. Demographic data, primary kidney diseases, comorbidities and previous RRT modalities were analysed. Episode(s) of peritonitis, total duration on PD therapy, switch to kidney transplantation or HD, and mortality rate were evaluated. Outcomes of elderly (≥ 65 years) and diabetic patients who were dropped out from PD were found out.&#x0D; Results: A total of 123 patients aged 18-83 years were included in the study. Forty percent of 123 PD patients initiated RRT with PD. The median time was found 1 month in the rest of the patients to transfer PD from other modalities. Renal transplantation was performed in 16.8% of patients during follow-up whereas 34.7% were transferred to HD after 41 months. Inadequate dialysis (40.7%), PD-related infections (29.6%), ultrafiltration insufficiency (18.5%), mechanical complications (11.1%) were the most common causes of switching from PD to HD. The duration of being under PD therapy was 36.5 months for 46 patients who died under PD therapy. Cardiovascular events (50%) and various infections (%35) were the leading causes of mortality. A total of 48 (43.2%) PD patients had at least one episode of peritonitis. Total duration on PD treatment, PD rate as initial RRT modality, the prevalence of hypertension and diabetes mellitus (DM), peritonitis rate, and use of automated PD were not significantly different between elderly (n=34) and adult individuals (18-65 years). The duration of being under PD therapy was longer for males than females (p=0.044) and the duration of PD therapy was similar in the dropped out patients with or without DM (p=0.205).&#x0D; Conclusion: A significant amount of patients received HD before initiation of PD (60%). Age is not be considered as a challenging barrier for PD initiation in Northern Cyprus. Precautions to prevent the development of peritonitis may contribute to extend the total duration of PD treatment.

Three-Year Outcomes in Kidney Transplant Recipients Switched From Calcineurin Inhibitor-Based Regimens to Belatacept as a Rescue Therapy.

Background: The long-term benefits of conversion from calcineurin inhibitors (CNIs) to belatacept in kidney transplant recipients (KTr) are poorly documented. Methods: A single-center retrospective work to study first-time CNI to belatacept conversion as a rescue therapy [eGFR <30 ml/min/1.73 m2, chronic histological lesions, or CNI-induced thrombotic microangiopathy (TMA)]. Patient and kidney allograft survivals, eGFR, severe adverse events, donor-specific antibodies (DSA), and histological data were recorded over 36 months after conversion. Results: We included N = 115 KTr. The leading cause for switching was chronic histological lesions with non-optimal eGFR (56.5%). Three years after conversion, patient, and death-censored kidney allograft survivals were 88% and 92%, respectively, eGFR increased significantly from 31.5 ± 17.5 to 36.7 ± 15.7 ml/min/1.73 m2 (p < 0.01), the rejection rate was 10.4%, OI incidence was 5.2 (2.9–7.6) per 100 person-years. Older age was associated with death, eGFR was not associated with death nor allograft loss. No patient developed dnDSA at M36 after conversion. CNI-induced TMA disappeared in all cases without eculizumab use. Microvascular inflammation and chronic lesions remained stable. Conclusion: Post-KT conversion from CNIs to belatacept, as rescue therapy, is safe and beneficial irrespective of the switch timing and could represent a good compromise facing organ shortage. Age and eGFR at conversion should be considered in the decision whether to switch.

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage.

The simultaneous cytological and metabolic investigation of various extravascular body fluids (EBFs) provides clinically relevant information about the type and intensity of the immune response in particular organ systems. The oxidative burst of professional phagocytes with the concomitant production of reactive oxygen species consumes a large amount of oxygen and is the cause of switch to the development of anaerobic metabolism. We assessed the relationships between percentages of neutrophils, aerobic and anaerobic metabolism, and tissue damage via the determination of aspartate aminotransferase catalytic activities (AST) in cerebrospinal fluid (CSF), pleural effusions (PE), abdominal effusions (AE), and synovial fluids (SF). EBFs with 0.0–20.0% neutrophils: 83.0% aerobic and 1.3% strongly anaerobic cases with median of AST = 13.8 IU/L in CSF; 68.0% aerobic and 9.0% strongly anaerobic cases with median of AST = 20.4 IU/L in PE; 77.5% aerobic and 10.5% strongly anaerobic cases with median of AST = 18.0 IU/L in AE; 64.1% aerobic and 7.7% strongly anaerobic cases with median of AST = 13.8 IU/L in SF. EBFs with 80.0–100.0% neutrophils: 4.2% aerobic and 73.7% strongly anaerobic cases with median of AST = 19.2 IU/L in CSF; 7.4% aerobic and 77.3% strongly anaerobic cases with median of AST = 145.2 IU/L in PE; 11.8% aerobic and 73.7% strongly anaerobic cases with median of AST = 61.8 IU/L in AE; 25.5% aerobic and 38.2% strongly anaerobic cases with median of AST = 37.2 IU/L in SF. The significant presence of neutrophils, concomitant strong anaerobic metabolism, and elevated AST in various EBFs are reliable signs of damaging purulent inflammation.

Three number processing systems: Different features and parallel activation

<p id="p00010">Clarifying the relationship among mechanisms underlying nonsymbolic numerical cognition is one of the most critical questions in the numerical cognition field. From a novel perspective, the hypothesis that three-number processing systems exists provides a plausible explanation for this relationship. According to this hypothesis, distinct mechanisms are involved in the number processing of nonsymbolic stimuli within different number ranges. Small numbers (1~4) can be appraised rapidly and errorlessly based on the activation of subitizing system. Moderate numbers are proposed to be processed spontaneously with a constant error rate of about 20% due to the activity of numerosity system. Typically, Weber’s law of number perception is demonstrated in this number range. For large numbers, the stimulus number relationship is suggested to be inferred indirectly via density analysis, and number processing, which is fast and has an error rate proportional to the square root of the stimulus number, is mediated by the activity of density system. <p id="p00010">A series of studies have revealed different behavioral features, as well as distinct Event-related potentials (ERP) features, among number tasks based on these three systems. For subitizing and density systems, better processing efficiency is demonstrated by a shorter reaction time and a lower error rate, whereas a higher dependence on attention resources is also a characteristic of these two mechanisms. Neither subitizing nor density mechanisms are correlated with math ability for children in school. For the numerosity mechanism, on the contrary, lower efficiency and independence of attention are shown, and the accuracy of numerosity comparisons is suggested to be significantly correlated with math scores for school children. ERP features are also suggested to be distinguishable for these three mechanisms. An early component related to attention is typically found under a subitizing mechanism rather than under numerosity or density mechanisms. P2p showed a distance effect, namely, higher P2p amplitude correlates with more errors in comparison tasks, as the ratio of the numbers to be compared approaches “1”, under both numerosity and density mechanisms. In general, the amplitude of P2p (about 200 ms after the onset of stimuli) is larger for the density mechanism compared with that for the numerosity mechanism, whereas the P2p component is more sensitive to the change in number within the numerosity range than within the density range. <p id="p00010">There are two major challenges for the three-number processing hypotheses. First, as proposed by some researchers, even when the numerosity and density mechanisms are distinguished by different modes of Weber fractions, more direct evidence is still needed to demonstrate that the processing bases of these two mechanisms are numerosity and density, respectively. Second, the narrow range described in the original hypothesis may induce discontinuity between the three-number processing hypotheses and the classical hypothesis, for example, the approximate number system hypothesis or ANS hypothesis. To solve these problems, it is proposed that the cause for switching from numerosity to density should be reanalyzed and that the hypothesis that the numerosity mechanism is activated in a wider number range should be considered. <p id="p00010">Some experimental evidence indicates parallel activation between subitizing and numerosity systems as well as between density and numerosity systems. The parallel activation hypothesis is also noteworthy. Multiple number processing systems could be activated simultaneously, and cognition relies on the system whose processing result is more precise to achieve the best processing results.

Factors Cause of Switching Shorter Regimen to Longer Regimen in Multidrug-Resistant/ Rifampicin-Resistant Tuberculosis Treated Patients in Dr. Soetomo Hospital Surabaya, Indonesia

Background: Indonesia started to implement the Shorter Regimen (STR) since 2017, but not all of MDR/RR-TB patients were treated with STR until the end of treatment. The presence of side effects of one orseveral drugs in the STR and the resistance to fluoroquinolone and or 2nd line injection drug after startingtreatment caused a switch in regimen from STR to a longer regimen. This study was conducted to evaluatethe factors that caused switch STR to the longer regimen.Methods: This was a descriptive study in MDR/RR-TB patients who received STR from October 2017to December 2019. Patients who switch their regimen were analyzed and determine the factors cause ofswitching STR to a longer regimen.Conclusion: The major cause of switching was due to the presence of resistance to fluoroquinolone and 2ndline injection drugs and incidence of prolonged QT. A diagnostic rapid test such as the line probe assay 2ndline TB drugs is absolutely a screening tool to determine MDR-TB patients, pre-XDR-TB or XDR TB assoon as the regimen is given. Monitoring and efforts to overcome prolonged QT side effects are also neededto prevent switch regimens that can affect the patient’s psychological condition.

Switching across direct oral anticoagulants: a real-life-setting pilot prospective study.

Crossover between direct oral anticoagulants (DOACs) has been underinvestigated, but happens frequently in clinical practice. The purpose of this study was to evaluate causes, rates and outcomes of a DOAC-to-DOAC switch. Patients receiving their first DOAC prescription at the Anticoagulation Center, Cardiology Dept, Bologna-Bellaria Hospital in 2017-2018 were consecutively included and prospectively followed up. DOAC-to-DOAC switch was the main outcome; causes of switch (cardiovascular events and noncardiovascular drug-related adverse events) had direct biannual assessment before and after the switch. Among 300 patients enrolled (mean age = 79.3 years, mean follow-up = 1.5 years), with no difference in cardiovascular risk factors depending on index DOAC, 13% underwent DOAC-to-DOAC switch, minor bleeding and noncardiovascular adverse events being the most frequent causes. Dabigatran carried a three-fold increase in risk of switch compared with other DOACs, but the mean age of patients who switched was 83. Factors leading to switch resolved in 87% of cases afterwards. Annual rates of cardiovascular/noncardiovascular V events did not differ before and after the switch. DOAC-to-DOAC switch happens in 9% of patients using DOAC each year, and seems not to impact rates of cardiovascular events after switch. Dabigatran, in the elderly, might be associated with a higher risk of DOAC-to-DOAC switch. Further studies are needed to confirm the long-term safety and effectiveness of switching paradigm.

CLINICAL-EXPERIMENTAL EXPERIENCE WITH RAPAMYCIN IN VISCERAL TRANSPLANTATION

Aim: Rapamycin (RAP) has recently demonstrated clear long-term benefits in visceral transplantation (VT). However, its use is limited to patients suffering FK side effects and there are no guidelines supporting the timing for a safe and effective switch. Our aim was to review our clinical and experimental experience in the use of RAP after VT. Materials and Methods: Our series of 107 VT was reviewed. Only patients who survived more than 3 months were included (n=82). They were divided in three groups according to the maintenance immunosuppressive treatment: FK (n=50), switched to RAP (n=24) and combined therapy (RAP+FK; n=8). Patients converted to RAP were divided in two subgroups: early RAP (<6 months after VT, n=12) and late RAP (>6 months after VT, n=20). Causes and timing to introduce RAP, rejection rate and survival were analyzed. We used an allogeneic VT rat model to analyzed RAP efficacy. Animals received no IS (controls), FK (0,6mg/kg/24hs) or different doses of RAP (1mg and 2mg kg/24h) (n=5 animals/group). Rejection was monitored by clinical scoring and histopathology after 14 days. Results: RAP was prescribed 10 months (0-99) after VT. Renal failure was the main cause of switching to RAP (28%), followed by hematological syndromes (25%). Rejection rate tended to be lower in patients with RAP, although the differences were not significant (FK 32%, RAP 25%, RAP+FK 37%; p=0.74). Graft survival at 1 and 5 years was significantly higher with RAP [FK 78%/48%, RAP 96%/83%, RAP+FK 86%/63% (p=0.013)]. Patient survival at 1 and 5 years was higher although not significantly in RAP group [FK 82%/64%, RAP 96%/83%, RAP+FK 86%/75% (p=0.27)]. No significant differences were found between early vs late RAP regarding rejection rate (33% vs 25%, p=0.61) graft survival at 1 and 5 years (83%/67% vs 100%/85%, p=0.15) and patient survival at 1 and 5 years (83%/75% vs 100%/85%, p=0.13). In the experimental model, RAP monotherapy did not show any improvement in survival (control: 9,75 ± 0.25 days; RAP: 11 ± 1 days) or clinical and histological signs of rejection compared to the control group (they both presented moderate-severe histological inflammation at the time of sacrifice). Animals receiving FK treatment did not show clinical signs of rejection and the histological alterations were indeterminate-mild at the time of sacrifice (10-14 days after VT). Conclusion: Patients switched to RAP had better survival compared to patients with standard immunosuppression. However, the improvement tended to be attenuated in those who were converted early. Experimental results showed that early RAP monotherapy at different doses had poorer results compared to FK groups. Further translational research is warranted to define the optimal timing and schedule for RAP usage.

76Causes, safety and outcomes of switching from the Initial direct oral anticoagulant to another in patients with non-valvular atrial fibrillation from a single-center prospective study

Abstract Background Crossover between direct oral anticoagulants (DOACs) in real-life setting has been under investigated, with electronic registry-based study missing minor bleedings and minor ischemic events. The purpose of this study was to evaluate the switch from a DOAC to another DOAC, the reasons and the clinical events which happened after the switch. Methods Patients (pts) receiving first DOAC prescription at the Anticoagulation Center from February 2018 to September 2019 were consecutively included and followed. Causes of switch/dosage change as well as events or adverse events not leading to switch were registered. Results Overall, 300 pts were included, mean age 79.3 ± 8.5, male 53.7% (n = 161). 220 pts were received DOAC being naïve (70.7%), while 88 (29.3%) transitioned from vitamin K antagonists. Mean follow-up was 1.5 years from first DOAC prescription. Most prescribed DOACs was rivaroxaban (n = 107), followed by apixaban (n = 82), edoxaban (n = 59) and dabigatran (n = 52). No significant differences in age, gender, CHA2DS2VASc or HASBLED score was detected. Throughout follow-up, 61 patients (20.3%) needed changes in anticoagulation regimen. 24 patients changed DOAC dosage (8%), while 40 patients changed anticoagulants (13.3%), 39 switched from DOAC to another DOAC, 1 from DOAC to warfarin. Annual DOAC-to-DOAC switching rate was 15.0% (95%CI 10.8-20.3). Prevalence of switch varied across DOACs: 28.8% of pts taking dabigatran switched vs 11.0%, 10.2% and 9.3% of those taking apixaban, edoxaban and rivaroxaban respectively (p &amp;lt; 0.05). Apixaban was the most commonly preferred DOAC after switch, with 43% of pts receiving it after crossover. Causes of switch included minor bleeding (n = 15), major bleeding (n = 3), non-cardiovascular adverse events (n = 14), drug interaction or surgery (n = 4), renal function worsening (n = 2) and low compliance (n = 1). Comparative risk analysis revealed that prescription of dabigatran was associated with a 3-fold increase in risk of switching treatment (OR 3.59, 95%CI 2.09-6.19) compared to other DOACs. Apixaban, rivaroxaban and edoxaban seemed to have similar profile in terms of long-term adherence to treatment . Cox regression analysis, taking into account age, weight, CHA2DS2VASc and HASBLED scores, revealed significant differences in temporal distribution of crossover, with pts in dabigatran more likely to change treatment (HR 2.5, p &amp;lt; 0.05). After switching, 34 out of 39 pts remained free from cardiovascular events and non-cardiovascular adverse events. One pt had minor bleeding, only 1 had major (non-fatal) bleeding, and none reported compliance issues. Non-cardiovascular adverse events completely resolved after switch . Conclusion Minor bleeding and non cardiovascular adverse events are the most common causes of switch, which has a rate as high as 15% year. Crossover between DOACs seems safe, and might therefore be considered after minor bleeding and non-cardiovascular adverse events

Sustainability and switching of biologics for psoriasis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The optimal treatment guidelines for psoriasis using biologics are limited. In addition to this, the administration of the original biologic may be terminated or switched to another biologic due to inefficacy, adverse effects, and economic burden. Our objective is to compare demographic characteristics between switched and non-switched groups and to identify the reason for switching among various original biologics in our setup.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We performed a retrospective cohort analysis of psoriatic patients on biologic treatment. Our analysis involved 42 patients, of which 19 were switched to the second biologic. The demographic characteristics and reason for biologic switching were noted and data analyzed between switched and non-switched groups.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; First line therapies were infliximab (IFX, n=10), etanercept (ETN, n=21), secukinumab (SEC, n=11) and switching required in 3 (30%), 11 (52%), 5 (45%) patients respectively. The reason for switching, in general, in our setup is inefficacy (n=10; 53%), non-availability (n=8; 42%) and adverse event (n=1; 5%). Small number of patients, single-centre study and retrospective design were the limitations.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Infliximab showed the least tendency to switch to the second biologic, however, it had adverse reactions. Inefficacy is the primary cause of switching. To the best of our knowledge, our study on Biologics switching is the first of its kind in the Indian scenario.&lt;/p&gt;

Predictive Factors for Thrombopoietin Receptor Agonist Free Responses in Chronic ITP Patients: A Multicenter Retrospective Study with Long-Term Follow-up

Background . In clinical practice, tapering off thrombopoietin receptor agonists (TPO-RA) in immune thrombocytopenia (ITP) is considered if therapy is no longer needed due to a decrease in the disease activity favoring sustained treatment-free responses (TFR). To date, there are no predictors to identify when this approach is likely to be successful, other than earlier start of TPO-RA, and robust platelet responses. Aim. To evaluate clinical predictors of TFR in a real-world cohort of ITP patients treated with TPO-RA by dealing with confounding variables that could be minimized at the stage of the analysis. Methods. In this retrospective, multicenter study from 19 secondary and tertiary Spanish hospitals, patients aged &gt;18 years with chronic ITP who had initiated TPO-RA (eltrombopag [EPG] or romiplostim [ROM]) between January 2012 and December 2014 were included. Data were collected from medical records (November 2016 to January 2018) on patient characteristics, history of disease and previous therapies, TPO-RA administration, response and discontinuation. Results. A total of 82 patients with a median age of 63 years (range 19-90 years), 59.9% females initiated TPO-RA (ROM, n=37; EPG, n=45). The median time from diagnosis of ITP to therapy with TPO-RA was 5.5 years (1.1-50.3 years). In all cases the TPO-RA was started with intention to treat indefinitely; the median initial doses of EPG were 350 mg/week (175-525 mg/week), and those of ROM 2.0 μg/kg/week (1.0-7.0 μg/kg/week). The median time on TPO-RA treatment was 2.9 years (0.1 to 5.6 years), and the median follow-up from start of TPO-RA until collection of data was of 3.9 years (1.3 to 5.6 years). A total of 29 patients (35.4%) switched TPO-RA during follow-up. The most frequent cause for switching was lack of efficacy (44.8% of cases -in all cases the initial TPO-RA was EPG-). Due to switching, 58 patients received ROM, and 53 were treated with EPG, yielding 122.3, and 100.8 patient-years of total exposure, respectively. During follow-up almost one half of the patients (47.6%, n=39) stopped TPO-RA. After a median of 1.4 years (0.1-3.3 yrs) under TPO-RA treatment, 19 patients (23.2% of the whole cohort) maintained TFR defined as platelet counts &gt;50x109/l for a median follow-up of 2.8 years (1.5-4.4 years) in the absence of any platelet increasing drug. Remarkably, while the specific TPO-RA that was discontinued did not influence the probability to achieve TFR (P=0.582), there was a trend towards receiving ROM as first TPO-RA and attaining sustained responses (P=0.073), while switching TPO-RA negatively predicted TFR (P=0.010). In univariate analysis with logistic regression, switching TPO-RA was associated with a 6.4 risk of not achieving TFR (P= 0.019). The overall comparison of the Kaplan-Meier curves indicated an association (log-rank P=0.041) among the initial TPO-RA that was prescribed and the probability of TFR (Fig 1A), but the estimated median time to achieve TFR was not reached for either TPO-RA. When switching and initial TPO-RA were considered, patients receiving ROM and not experiencing switching were the best performing group in terms of achieving TFR; the median time to taper off the drug and sustain platelet responses was 3.3 years (95% CI 2.7-4.0 years) (Fig. 1B). Conclusion. In this observational research analysis, we have tried to minimize the possible bias of some studies that could mistakenly attribute TPO-RA induced TFR, when in fact it may be the natural course of the underlying disease. By analyzing a group of chronic ITP patients with a particularly poor baseline prognosis (median time from diagnosis 5.5 years) we address potential confounding variables by disease severity. Our data show that assuring that long duration under TPO-RA therapy is provided (median of 3.3 years), one half of chronic ITP patients treated with ROM and not undergoing switching can achieve TFR. Disclosures Mingot-Castellano: Roche: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Takeda: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Novonordisk: Consultancy; CSL Behring: Consultancy. Jarque:Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau. Campos:Novartis: Speakers Bureau; Amgen: Speakers Bureau. Lopez Fernandez:Amgen: Consultancy, Speakers Bureau. Casado:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Álvarez Roman:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau.

Sequence of Second Generation Tyrosine Kinase Inhibitors (TKIs) in the Treatment of Patients with Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukaemia - Real World Experience in the UK

Sequence of Second Generation Tyrosine Kinase Inhibitors (TKIs) in the Treatment of Patients with Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukaemia - Real World Experience in the UK

PF690 PREDICTORS OF THERAPY FREE RESPONSES IN ITP PATIENTS RECEIVING TPO‐RA. RESULTS FROM A SPANISH MULTICENTER STUDY

Background:Thrombopoietin receptor agonists (TPO‐RA) are a well‐established treatment in patients with primary immune thrombocytopenia (ITP). Sustained treatment‐free responses (TFR) after TPO‐RA discontinuation in adult ITP have been reported; yet, to date there are no predictors to identify in which patients this approach is likely to be successful.Aims:To evaluate clinical predictors of TFR in a real world cohort of ITP patients treated with TPO‐RA.Methods:Patients aged &gt;18 years with primary ITP who had initiated TPO‐RA (eltrombopag [EPG] or romiplostim [ROM]) treatment between January 2012 and December 2014 were included in this retrospective, multicenter study from 19 secondary and tertiary Spanish hospitals. Data on patient characteristics, history of disease and previous therapies, TPO‐RA administration, response and discontinuation were collected from medical records.Results:A total of 121 patients with a median age of 63 years (range 19–96 years), 59% females initiated TPO‐RA as long‐term therapy (ROM 54; EPG 67). Sixty‐eight percent of the patients treated with TPO‐RA met criteria for chronic, 16% for newly diagnosed and 16% for persistent ITP. The median time on TPO‐RA treatment was 35.2 months (1 to 67.3 months), and the median follow‐up from start of TPO‐RA until collection of data was 44.9 months (23.8 to 67.5 months). A total of 39 patients (32.2%) switched TPO‐RA during follow‐up. The most frequent cause for switching was lack of efficacy (48.7% of cases ‐in 89.5% the initial TPO‐RA was EPG‐). Due to switching the exposure to both TPO‐RAs was similar during follow‐up; 80 patients received ROM and a similar number was treated with EPG, with total exposure (years) of 161.0, and 168.3, respectively.During follow‐up almost one half of the patients (46.3%, n = 56) tapered‐off the TPO‐RA; 10 out of the 37 cases that discontinued ROM had previously received EPG, and 4 out of the 19 that stopped EPG had switched from ROM. After a median of 432 days (29–1344) under TPO‐RA treatment, 35 patients (28.9%) maintained TFR defined as platelet counts &gt;50x109/l for more than 6 months. In 4 of these 35 cases, TPO‐RAs were reintroduced due to loss of response after a median TFR of 20.5 months. Potential predictors of TFR in the remaining 31 patients (25.6%) with sustained platelet counts in the absence of any agent meant to increase platelet count (median 32 months, 8–217) were analyzed. No specific patient feature (e.g. age, comorbidities, ITP duration, previous treatments), bleeding, previous therapies nor phase of disease seemed to consistently predict for sustained response off therapy. However, univariate analysis (Chi‐square) did identify statistically significant predictors of TFR. Interestingly, while the specific TPO‐RA that was discontinued did not influence the probability to achieve TFR, receiving ROM as first TPO‐RA was positively associated with TFR (P = 0.010), while switching TPO‐RA negatively predicted sustained platelet responses (P = 0.002). In multivariate analysis with logistic regression both variables predicted significantly higher odds of TFR (Table 1).Summary/Conclusion:Platelet response following TPO‐RA cessation is sustained in 25.6% of adult patients with primary ITP. Although published studies have not identified a predictive factor of sustained response after TPO‐RA discontinuation, in this long‐term follow up analysis, ROM as first TPO‐RA being administered, and no need of TPO‐RA switching are factors that positively correlate with the probability to achieve TFR.image

Efficacy and safety of switching from ticagrelor to clopidogrel during the early and late phase in acute coronary syndrome patients after percutaneous coronary intervention

In patients with acute coronary syndrome (ACS), treatment using ticagrelor demonstrated significant ischemic benefits over clopidogrel; however, it was associated with increased bleeding complications leading to frequent de-escalation to clopidogrel. The objective of the present study was to investigate the efficacy and safety of de-escalation in early and late phase after percutaneous coronary intervention (PCI). We performed a retrospective study of 4678 ACS patients from March 2016 to April 2017 who initially received ticagrelor then de-escalated to clopidogrel and categorized them into Group 1: early phase (1–30 days) and Group 2: late phase (>30 days–1 year) switching groups. The primary efficacy endpoints included cardiovascular death, definite/probable stent thrombosis, myocardial infarction, unplanned revascularization, and stroke. The safety endpoint was Bleeding Academic Research Consortium classification 3 or 5 bleeding events within 1 year after PCI. The incidence of switching occurred in 1019 patients; 380 (37.3%) in Group 1 (median 14 days, interquartile range 4–30 days) versus 639 (62.7%) in Group 2 (median 180 days, interquartile range 90–270 days). The ischemic endpoints occurred in 53 (13.9%) patients in Group 1 versus 35 (5.4%) in Group 2 (HR 1.93,95%CI 1.22–3.08, p < .0001). There were no significant differences of major bleeding events (HR 0.91; 95%CI, 0.58–1.43, p = .90) seen between the groups. The main cause for switching between the two groups was due to BARC 1 or 2 bleeding types. Early de-escalation from ticagrelor to clopidogrel during the initial 30 days after ACS was associated with higher risk of ischemic events when compared with switching beyond 30 days.

RETROSPECTIVELY ASSESSING THE EFFICACY OF AGOMELATINE IN BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS OF DEMENTIA

Introduction Behavioral and psychologic symptoms of dementia (BPSD) are sources of increasing stress to patients and caregivers and escalate the cost of overall care for dementia cases. Moderate and severe BPSD often need medical treatment to improve symptoms. However, the use of antipsychotic medications or antidepressants often leads to side effects and increases disability. Agomelatine is a selective melatonergic (MT1/MT2) agonist that has normalizing effect on disturbed circadian rhythms and disrupted sleep–wake cycles. Its activity of 5HT-2C receptor antagonism is associated with antidepressant and antianxiety and increases slow-wave sleep. Agomelatine is also considered to be antioxidant and anti-inflammatory activity. It restores stress-affected hippocampal neuronal activity and promotes adult hippocampal neurogenesis and neuroplasticity. Previous clinical findings prompt that agomelatine can improve the BPSD of dementia patients. This retrospective cohort study was used to evaluate the BPSD of dementia cases before and after agomelatine use. Methods Dementia cases who ever received agomelatine treatment for depressive symptoms in a general hospital for past 2.5 years were fully reviewed. Their chart records, including the scores of Neuropsychiatric Inventory (NPI), were recorded. The changes of NPI score were used to evaluate the difference of psychological and behavioral symptoms before and after agomelatine use. The linear mixed-effect model is used to model the changes by controlling the confounding effects of age and sex, hypnotics, antipsychotic drugs, and the adjuvant drug –Mesyrel using. The side effects of agomelatine use were also invest. This study was approved by the institutional review board of National Cheng Kung University Hospital. Results There are 75 cases (male 26, female 49) with Alzheimer's Dementia (AD) 25, Dementia with Lewy Bodies (DLB) 21, Vascular Dementia (VaD) 15, Mixed type dementia 9, and other type dementia 5 cases having both NPI records, pre-and post-agomelatine use 3 months or more. The mean age is 80.7 years old. The dose of agomelatine is from 12.5mg to 50mg per day. The severity and distress of NPI records all show improvement after agomelatine use (p=0.001), especially in the items of delusion, hallucination, agitation/aggression, depression/dysphoria, anxiety, disinhibition, irritability/lability, motor disturbance, sleep/nighttime behavior disturbance (p Eight cases discontinued from agomelatine use due to side effects: 6 with headache, oversleep, dizziness; 1 ever had violence in the midnight, and 1 increased falling down risk in the night. The causes of switching from other antidepressants (such as sertraline, citalopram, escitalopram, paroxetine, venlafaxine, duloxetine, mirtazepine, bupropion, imipramine, doxeine or trazodone) to agomelatine were depression related symptoms not improved or the side effects of using these antidepressants. These side effects include psychomotor slowing, drowsiness or insomnia, dizziness, fatigue, weak, increasing extrapyramidal symptoms, loss of appetite, constipation, bruising or increasing skin itching. Conclusions Agomelatine is effective on improving behavioral and psychological symptoms of dementia, no matter in depression, sleep disturbance, delusion, hallucination, or aggression. The start low and go slow rule should be considered since side effects of headache, dizziness, sedation or triggering the fall. This research was funded by Agomelatine is effective on improving BPSD.

Russian Experience of Bosutinib Use in Chronic Myeloid Leukemia Patients in Routine Clinical Practice

Background. The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKI) have diminished death probability and have changed the disease course. Achievement of complete cytogenetic response (CCyR) and major molecular response (MMR) are serve as warranties for freedom of progression and death from CML. There are many of CML patients are needed to change of initial TKI therapy with choice of the most efficient and safe drug for continuous life-long therapy to reach the optimal results of CML treatment. The newest of registered TKI drug in Russia is Bosutinib which has dual BCR-ABL and SRC kinase inhibitory activity and had showed good tolerability and efficacy in case of other TKIs resistance or intolerance.Aim. To analyze of own Bosutinib experience in patients with chronic myeloid leukemia with other TKIs resistance or intolerance and to make comparison with clinical trial results.Materials and methods. Clinical trials results from peer-reviewed journals. Outpatients charts of 51 patients (25 male and 26 females) with CML. Disease phase at the moment of Bosutinib therapy initiation was as follows: chronic - 37; acceleration - 8, blastic - 6. Bosutinib was used in the next lines of TKI therapy: second - 10; third - 18; fourth - 23. The indications for Bosutinib therapy were: intolerance to previous TKI - 21; resistance to previous TKI - 30.Results. Median of therapy duration was 6 months (1-50 months). The adverse events and tolerability of Bosutinib were similar with clinical trials data. The treatment was withdrawn by the adverse event only in 5 (10%) patients. The rates of the responses in the whole group of patients were as follows: CHR - 88%, stable in 76%; CCyR - 39%, stable in 37%, MMR - 31% and was 25% at the last follow-up. The Bosutinib efficacy in real life settings was slightly higher than clinical trials data. The factors influencing treatment responses were: disease phase, cause of switching to Bosutinib, line of therapy and presence and kind of BCR-ABL mutations, Therapy was continued in 22 (43%) patients, most them achieved stable optimal treatment response (CCyR and MMR).Conclusions. Bosutinib is a real alternative to other tyrosine kinase inhibitors and has its own mechanism of action and adverse events profile. The use of Bosutinib in real life clinical practice settings showed its efficacy and tolerability and could serve as base for recommendation to apply Bosutinib in hematology practice in Russia. DisclosuresNo relevant conflicts of interest to declare.

Anatomic and surgical factors affecting the switch from minimally invasive transthoracic occlusion to open surgery during ventricular septal defect repair.

This study aimed to investigate the specific causes for switching patients from minimally invasive transthoracic occlusion to surgical repair under cardiopulmonary bypass (CPB). By retrospectively analyzing 340 cases, we sought to provide the clinical reference for improving the success rate of minimally invasive transthoracic device closure of ventricular septal defect (VSD). Among the 340 patients who underwent transthoracic closure of VSDs in the past 3 years at our hospital, 26 patients needed to be switched to surgical repair under CPB due to failure of transthoracic closure. We investigated the causes by retrospectively analyzing the findings from preoperative transthoracic echocardiography (TTE), intraoperative transesophageal echocardiography (TEE) and surgical exploration. Among the 340 patients who underwent transthoracic closure of VSDs, 26 patients (7.65%) were switched to surgical repair under CPB, which included 11 cases of membranous aneurysm (13.10%), 13 cases of perimembranous type (6.22%) and 2 cases of intracristal type (5.00%) according to their anatomic classifications. Among the 186 patients who underwent transthoracic closure during the first 17 months, 20 patients (10.75%) were switched to surgical repair under CPB. The main causes were failure of the delivery system to pass through the VSD in 7 patients, obvious residual shunts after releasing the occluder in 5 patients, significant shedding or shifting after releasing the occluder in 4 patients, significant regurgitation in adjacent valves in 3 patients and severe intraoperative complication (bleeding) in 1 patient. Among the 154 patients who underwent transthoracic closure during the late 17 months, 6 patients (3.90%) were switched to surgical repair under cardiopulmonary bypass. The main causes were significant residual shunts after releasing the occluder in 3 patients, significant regurgitation in adjacent valves in 2 patients after releasing the occluder and failure of the delivery system to pass through the VSD in 1 patient. Among all the anatomic classifications, membranous aneurysm VSD had the highest risk for switching from minimally invasive transthoracic closure to surgical repair under CPB. During the early period, the surgeons were not yet skilled with the minimally invasive transthoracic closure procedure, and the main causes of switching to surgical repair under CPB were that the delivery system could not pass through the ventricular septal defect and significant residual shunts persisted after releasing the occluder. In contrast, in the late period, the surgeons were skilled with the minimally invasive transthoracic closure procedure, and the main causes were significant residual shunts and obvious regurgitation in adjacent valves after releasing the occluder.