Real Word Evidence Research Articles

Effectiveness and safety of secukinumab updosing in patients with moderate to severe plaque psoriasis: data from the PURE registry

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator’s Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.

Rethinking rectal cancer management through COVID: Real word evidence in a public hospital in the south of Brazil.

e15620 Background: Treatment of locally advanced rectal cancer is based on a combination of radiotherapy and chemotherapy, either as adjuvant, neoadjuvant or total strategies. Short course radiotherapy followed by neoadjuvant chemotherapy, as described in the RAPIDO trial, was chosen by our Oncology, Radiotherapy and Coloproctological tumor board at Hospital de Clínicas de Porto Alegre during the COVID19 pandemic as a measure to reduce hospital visits and thus the possibility of transmission and infection by the SARS-COV-2 virus. Methods: We performed an observational analysis, including all patients treated with short course radiotherapy for locally advanced rectal cancer, at the Hospital de Clínicas de Porto Alegre in the period between January 2020 and March 2023. Metastatic patients were included, either treated with curative or palliative intent. Demographic characteristics, clinical staging, timing of chemotherapy, radiotherapy and surgery were analyzed. Clinical response was evaluated through sigmoidoscopy and clinical rectal exam. Patients with complete clinical response were offered the watch and wait strategy or surgery, after careful discussion of the possible benefits and risks. Results: Ninety-six patients were submitted to short course radiotherapy in the period described. Seven (7) patients were excluded; 89 patients were included in the final analysis. Fifty-five percent were male; mean age was 62 ±12.5 years; 52.8% were ECOG 1 at the diagnosis. Median CEA value at diagnosis was 7 ng/mL (CI 95%:4.4 - 9.8). Sixty-four percent were stage III, 31.4% stage IV, 3.3% stage II. Ninety-eight percent completed the programmed radiotherapy treatment. Only two patients received less than 25Gy. Forty-nine percent of patients completed the whole planned chemotherapy treatment; 15.7% were treated with palliative intent chemotherapy and 5.6% couldn’t receive chemotherapy for other reasons. Clinical response data were available in 62 patients: the main reason for unavailable clinical response was metastatic disease. Disease control was achieved in 98.4% of the cases, with only 1 patient having progressive disease during treatment (1.6%). The overall clinical response rate was 72.6%, 25.8% had stable disease and 24.2% complete clinical response. Fifteen of the 16 patients that presented with complete clinical response opted into a watch and wait strategy, achieving a 1-year disease free survival of 86.6%. Conclusions: Adopting the RAPIDO approach had a positive outcome in our advanced rectal cancer population. Short course radiotherapy followed by chemotherapy achieved excellent rates of disease control. Almost 25% of the non-metastatic patients undergoing RAPIDO treatment achieved complete clinical response opting into a watch and wait program.

EPH211 Treatment Patterns and Clinical Characteristics of Patients Diagnosed with Metastatic NSCLC in Hmo from Colombia: A Real Word Evidence Study

EPH211 Treatment Patterns and Clinical Characteristics of Patients Diagnosed with Metastatic NSCLC in Hmo from Colombia: A Real Word Evidence Study

Exploring the prognostic role of complex karyotype in chronic lymphocytic leukaemia patients treated with venetoclax-based regimens.

Although the unfavourable prognostic role of complex karyotype (CK) in chronic lymphocytic leukaemia (CLL) patients treated with chemoimmunotherapy has been clarified, its impact on the outcome of patients being treated with novel targeted agents, and especially with venetoclax-based regimens, remains to be resolved. In fact, only few studies, utilizing data derived from clinical trials (e.g. MURANO, CLL14, GAIA-CLL13), specifically focus on this topic while real-word evidence is missing. In our real-life retrospective study conducted on 61 patients with CLL and treated with venetoclax-based regimens in any therapeutic line, we documented a remarkable lower progression-free survival in patients harbouring both CK and high CK, while overall response rate (including complete remissions and partial remissions) and overall survival are not affected by CK in our population.

Effectiveness and safety of Lacosamide in pediatric patients with epilepsy under four years: Results from a prospective cohort study in China

BackgroundLacosamide (LCM) has shown promising efficacy and safety outcomes in clinical trials. However, the evidence is limited among pediatric patients especially under four years in real-world. The study investigated the treatment outcomes and safety of LCM in patients under four years based on the data of the epilepsy registry of Children in China. MethodsA prospective cohort study was conducted among patients under 4 years who newly received LCM as monotherapy or adjunctive therapy. The treatment outcomes were measured by retention rate of LCM, 50 % response rates and seizure-free rates during follow-up. The retention rate of LCM was assessed using the Kaplan-Meier survival model. Adverse events were reported as a percentage of all participants. ResultsOf 109 participants (mean follow-up: 18.6 months), 59 received LCM as monotherapy and 50 as adjunctive therapy. Sixty patients had focal epilepsy, 44 had generalized epilepsy and 5 had combined generalized and focal epilepsy. 70 % of patients in the monotherapy group and 41 % in the adjunctive therapy group remained on LCM treatment without additional treatments for at least one year. In patients with monotherapy, 50 % response rate and seizure-free rate were 75 % and 56 % at 12 months, respectively. In adjunctive therapy group, these rates were 51 % and 36 %, respectively. Lower baseline seizure frequency in both treatment groups (monotherapy: p < 0.001; adjunctive therapy: p = 0.02) and younger age groups within the monotherapy group (P = 0.04) correlated with a higher LCM retention rate. Adverse events were reported by 15 patients (13.8 %), with somnolence being the most common (7 of 15 patients). ConclusionWith a comprehensive information and high-quality of data, the study demonstrates the effective treatment outcome and safety of LCM. The study adds reliable evidence to exiting real-word evidence of LCM in the specific age group of patients with epilepsy to fill the evidence gap.

Cenobamate as add-on therapy for drug resistant epilepsies: effectiveness, drug to drug interactions and neuropsychological impact. What have we learned from real word evidence?

Background: Cenobamate (CNB) is an anti-seizure medication (ASM) approved in 2021 in Europe for adjunctive treatment of focal-onset seizures in adults who were not adequately controlled with at least two previous ASMs. Methods: seizure outcome, treatment-emergent adverse events, neuropsychological profile, and blood levels of CNB and concomitant ASM were analyzed in a real world setting in two different Italian epilepsy centers in the context of CNB early access program. All patients performed a general cognitive evaluation, while 32 patients underwent the administration of a battery of neuropsychological tests at baseline and 6months after CNB treatment. We performed CNB quantification in plasma in 31 patients at different doses in the range of 100-400mg/day (65 measures). Results: we enrolled 54 patients with a median age of 27.9years. The mean follow-up was 10.7months. Most (91%) completed the efficacy analysis. At last follow-up visit, a 69.5% median seizure reduction was registered. Thirty-two patients (59.2%) had a ≥50% reduction of seizures that was ≥75% in 20 (42.0%) cases, whilst 10 (20.2%) patients were seizure-free. The most common adverse events were somnolence (53.1%), dizziness (28.1%) and diplopia (12.5%). The correlation between CNB dose and plasma concentration, revealed a significant linear correlation (r = 0.86, p < 0.0001), and there was a significant difference in mean plasma concentration/dose administered ratio (C/D ratio) between patients taking or not at least one inducer (0.10 ± 0.04 [(μg/mL)/(mg/day)]; n = 47 vs. 0.13 ± 0.05 [(μg/mL)/(mg/day)]; n = 18, p = 0.04). CNB dose was inversely correlated (r = -0.31, p = 0.02) to the C/D ratio of Carbamazepine blood levels. and positively correlated (r = 0.74, p < 0.0001) with an increased plasma concentration of the active Clobazam metabolite N-desmethylclobazam. General Anxiety Disorder-7 showed a significant improvement of score from baseline evaluation of 6.82 to follow-up 6months evaluation of 4.53 (p = 0.03). Conclusion: In this real-world study, we registered a clinically meaningful reduction in seizure frequency after CNB administration in most patients along with a good tolerability profile. CNB treatment is correlate to a reduction in symptom severity of anxiety score. Plasma levels measurements confirm that CNB acts both as "victim" and as "perpetrator" of drug-drug interactions.

OP39 Real-World Evidence Of Post-Incorporation Use Of Monoclonal Antibodies For Psoriasis In The Brazilian Public Health System

IntroductionPsoriasis is an immune-mediated chronic inflammatory disease that can affect the skin, joints, and nails. The treatment of the disease is offered by the Brazilian Public Health System (SUS) in accordance with the guidelines of the Ministry of Health. The aim of this study was to analyze real-world data (RWD) on the implementation and use of monoclonal antibodies (mAbs) for the treatment of psoriasis in the SUS.MethodsThis is a descriptive study that used national administrative data on drug dispensing from the Open Room for Health Intelligence Situation (SABEIS-SUS) from October 2019 to December 2021. Adult individuals (≥18 years) with vulgar (L40.0), generalized pustular (L40.1), gutata (L40.4) and other (L40.8) psoriasis who used the mAbs adalimumab, etanercept, risankizumab, secukinumab and ustekinumab were included.ResultsThe year of implementation of mAbs for the treatment of psoriasis in the SUS was October 2019 (adalimumab, etanercept and secukinumab) and May 2020 (ustekinumab). Risankizumab was implemented in April 2022. The number of individuals using mAb grew from 366 in 2019 to 10,146 in 2021. In 2019, 2020 and 2021, the proportion of individuals using each mAbs was 62.3 percent, 46.2 percent and 35.4 percent (adalimumab), 7.9 percent, 3.3 percent and 2.7 percent (etanercept), 29.8 percent, 33.8 percent and 30.5 percent (secukinumab), 0 percent, 16.7 percent and 31.4 percent (ustekinumab), respectively.ConclusionsThe number of mAbs users has greatly increased from 2019 to 2021, which may indicate a successful implementation of the psoriasis treatment in SUS. Most individuals used adalimumab in the year of the first implementation. However, the proportion of users of this mAb has greatly decreased after the implementation of ustekinumab. This reduction should not be so expressive since adalimumab and ustekinumab are recommended in different lines of treatment. The low proportion of etanercept use may be due the fact the medication is indicated for individuals up 18 years of age. This study provides important real-word evidence for monitoring the implementation of mAbs for psoriasis treatment in Brazil.

UM171 Expanded Cord Blood Transplantation Outcomes Compare Favorably to All Different Stem Cell Sources: An EBMT Registry Case-Control Analysis

Background: Cord blood (CB) transplantation (CBT) has several advantages compared with other graft sources, such as permissive human leucocyte antigen (HLA) mismatches, and low risk of chronic graft-versus-host disease (GVHD) and relapse. However, CBT has fallen into disfavor because of its high risk of non-relapse mortality (NRM) and prolonged hospitalization due to its low cell dose. Furthermore, the need for the rare large cord bloods (CBs) leads to selection of poorly HLA-matched CBs, known to further increase NRM. UM171 is a small molecule that expands hematopoietic stem cells. A phase I-II study of a single UM171-expanded, myeloablative and reduced intensity CBT for patients with high-risk hematologic malignancies who lacked a donor, demonstrated prompt neutrophil engraftment, the ability to use smaller, better HLA-matched CBs, and a low NRM of 5% (Cohen S et al. Lancet Haematol 2020). The aim of the current analysis was to compare outcomes after a UM171 CBT to real-world cohorts of 6 other stem cell sources identified in the European Society for Blood and Marrow Transplantation (EBMT) registry. Methods: This is a retrospective study comparing 22 adults who received a single UM171-expanded CBT in the phase I-II study between 2016-2018, to 6 cohorts of patients allografted from different stem cell sources and reported to the EBMT registry. Control patients were eligible if they had received a myeloablative or reduced intensity allogeneic transplant for a hematologic malignancy in Europe during 2010-2021, were between the ages of 18-65 years, and had a Karnofsky performance status (KPS) score ≥70. The different donor control cohorts were: 1) CB, single or double units, with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) for GVHD prophylaxis, 2) 10/10 HLA-matched unrelated donor (MUD) peripheral blood stem cells (PBSC) with a CNI and MMF or methotrexate (MTX), 3) 10/10 MUD bone marrow (BM) with a CNI and MMF or MTX, 4) 9/10 HLA-MUD BM or PBSC (9/10 UD), 5) T cell replete haploidentical donor (haplo) BM or PBSC, and 6) matched sibling donor (MSD) BM or PBSC. Exclusion criteria included in vitro manipulated grafts and CBT recipients who received anti-thymocyte globulin or alemtuzumab. Patients were directly matched for disease and status at transplant and propensity score matching was used for prior allograft, age, KPS, and conditioning regimen. Endpoints included engraftment, GVHD, NRM, relapse, progression-free survival (PFS), overall survival (OS), and GVHD-free relapse-free survival (GRFS). The EBMT attempted to identify 3 controls for each patient. If no control was identified for a UM171 patient, the latter was excluded from the analysis. Results: Between 17 and 21 UM171 CB patients were compared to 36 to 62 controls depending on the donor group as 1-3 controls could not be identified for each patient (Table 1). Median follow-up for the UM171 group was 36 months and generally longer for the controls. Neutrophil engraftment with UM171 CB was similar to all donor groups except slower for CB and MUD BM. Platelet engraftment was consistently slower for UM171 CB except when compared to conventional CB. The incidence of severe acute GVHD was similar across all donor groups. As there was no severe chronic GVHD in the UM171 group, the latter was associated with less extensive/severe chronic GVHD compared to MUD (PBSC and BM) and MSD. There was a trend towards lower NRM for UM171 CB compared to haplo and 9/10 UD but it did not reach statistical significance. PFS, OS and GRFS were all better with UM171 CB compared to haplo. Finally, GRFS was improved with UM171 CB when compared to MUD PBSC (Figue 1), 9/10 UD, and MSD. Conclusions: This registry matched case-control analysis demonstrated real-word evidence suggesting UM171-expanded CBT recipients have improved outcomes compared to other donor types. More specifically and due to the absence of severe chronic GVHD with UM171 CB, GRFS was better with UM171 CB when compared to other graft sources except for CB and MUD BM. Also, OS and PFS were superior with UM171 CB compared to haplo donors. Limitations of this study included the small number of UM171 patients, the inability to identify controls for each case, and certain missing data for the controls. UM171 expansion of CB appeared to achieve the desired outcome of maintaining benefits of CB while removing its disadvantages. Thus, prospective randomized studies are warranted to confirm these results.

Real-Word Experience of CAR T-Cells in Patients with Relapsed/Refractory Follicular Lymphoma : A Descart Registry Analysis from the Lysa

Background: Anti-CD19 CAR T-cells have revolutionized the treatment of aggressive B-cell non-Hodgkin lymphomas (NHL) by demonstrating durable responses. Although follow-up remain short, axicabtagene ciloleucel (axi-cel, ZUMA-5) and tisagenlecleucel (tisa-cel, ELARA) demonstrated promising complete response rates (CRR) of 86% and 69%, respectively, in phase II trials including relapsed or refractory (R/R) follicular lymphoma (FL).. Tisa-cel and axi-cel are now approved after at least 2 lines of systemic therapy by the FDA. Few real-word evidence (RWE) data have been reported so far. Methods: Patients were eligible if aged &amp;gt;18 years, had FL histology (grade 1-3A) and had received at least 2 previous treatment lines for tisa-cel and 3 for axi-cel according to the French early access program label. From Dec 2021 to Jan 2023, a total of 112 patients were included in early access program by 21 French centers and in DESCAR-T registry (NCT04328298), among them 87 were infused with a CAR product. At the data cut-off on March 2023, 70 had at least 1 month of follow-up (FU) with PET-CT evaluation, and thus were considered for the safety and efficacy sets (62 tisa-cel and 8 axi-cel,). Results: Patient and disease characteristics were as follows: 46 males (65.7%), median age 62 years (range: 34-79), 3 median prior lines of therapy (range 2-9, including bi-specific antibody in 12.9% and autoSCT in 44.3%), FLIPI 0-2 in 40.5% and 3-5 in 49.5%, bulky disease (&amp;gt;5cm) in 22%, and LDH &amp;gt; N 52.2%. POD24 after 1 st systemic immunochemotherapy (IC) was reported in 44 patients (62.8%). Before CAR T-cell infusion, 58.6% of patients received a bridging therapy (20 (48.8%) chemotherapy, 25 (61%) monoclonal antibodies, 4 (9.8%) kinase inhibitors, 15 (36.6%) lenalidomide, and 3 (7.3%) radiotherapy). All patients but one received a fludarabine and cyclophosphamide-based lymphodepletion. Median time from order to infusion was 48 days (range 34-204), and 41 days (30-328) from leukapheresis to infusion. Median FU was 7.3 months [6.4; 8.2] from product order, and 5.4 months [3.4; 6] from CAR infusion. Best ORR and CRR were 97.5 and 87.5%, respectively with 72.5% of patients in CR at 1 month with projected DOR and DOCR of 72.4% [56.8; 83.1%], and 79.7% [62.7%; 89.6%], respectively. Projected 6-months PFS, OS, were 71.8% [95% CI, 56.6%; 82.4%], 97.4% [83.2%; 99.6%], respectively. Fifteen (21.4%) patients progressed (median time from infusion to first relapse: 3 months (range 1-10 mo). Only one patient died from lymphoma progression. Any-grade CRS and ICANS were reported for 74.3% and 27.1% of patients, but grade 3-4 CRS/ICANS were very unfrequent,1.4% and 4.3%, respectively. No grade 5 was reported. Persisting grade 3-4 hematologic toxicities at 1 and 3 months were: neutropenia (50% and 12.3%), thrombocytopenia (18.6% and 0%), and anemia (8.6% and 0%). Medically relevant bacterial and viral infections were reported in 20% and 14.3% of patients, respectively. Conclusions: Although longer FU is needed to assess disease control, RWE data from the DESCAR-T registry confirm the excellent response rates and safety profile of CAR T-cells in R/R FL after at least 2 lines of previous therapy.

Predictors for the effectiveness of 75 mg risankizumab in treating psoriasis-A real-word evidence from a 52-week retrospective study.

In the registration trial of risankizumab for patients with moderate-to-severe psoriasis in Japan, similar Psoriasis Area Severity Index (PASI) responses were observed for 75 mg or 150 mg risankizumab at most time points up to 52 weeks, except for PASI 100 at week 16. The use of 75 mg risankizumab offers an attractive option considering the high cost of risankizumab. However, it is unknown whether patients with mild-to-moderate psoriasis respond similarly, and the efficacy data of non-Japanese patients is also lacking. We retrospectively included 30 consecutive Chinese patients receiving half-dose (75 mg) risankizumab as scheduled up to 52 weeks. Compared with biologic-experienced group, biologic-naive group had a significantly higher PASI 50/75/90/100 achievement (p = 0.0098/0.0039/0.0016/0.0054) at week 52. PASI 50/75/90/100 curves in biologic-naive group (p = 0.0117/0.0239/0.0143/0.0269) were also significantly higher when analysed generalized estimating equations (GEE) model. Though there was no statistically significant difference in terms of PASI 50/75/90/100 responses at any time points between those with body weight ≦ 65 kg and those >65 kg, a tendency of secondary failure was noted in those >65 kg from week 40 onwards. Patients who were both biologic-naive and weighed ≦ 65 kg achieved sustained PASI 50/75/90 responses from week 16/28/40 onwards, respectively, indicating that they could be considered as potential candidates for 75 mg risankizumab. Though PASI 75 curve in patients without diabetes mellitus (DM) surpassed that in patient without DM, curves of other parameters did not reach significance when analysed by GEE model. There was no HBV, HCV or TB reactivation, nor other new safety signals during the 52-week observational period. Providing risankizumab with flexible dosing options is beneficial in clinical practice considering the high cost of this medication.

Applicability of the OPTA Questionnaire for Patients with Stable Ischemic Heart Disease in Indian Clinical Practice: A Cross-sectional, Real-word Evidence Study.

Angina is the symptomatic form of stable ischemic heart disease (SIHD). The OPtimal Treatment of Angina (OPTA) questionnaire was developed and validated to overcome the lack of a standardized and accurate tool to assess patients' clinical conditions with SIHD. This study aimed to understand the applicability of OPTA in patients with SIHD in routine clinical practice in India. In this cross-sectional, single-visit study, 344 patients with SIHD were enrolled. Study endpoints were physicians' agreement on the applicability of OPTA, the usefulness of OPTA in assessing degree of impairment in daily activities of patients, and its positive predictive value (PPV). All enrolled patients completed the study. The mean [standard deviation (SD)] age was 56.6 (10.77) years, with a majority of patients being male (69.5%) and on antianginal treatment for &gt;1 year (80.4%). Physicians of all participating patients agreed that the OPTA questionnaire could accurately assess whether treatment received by patients was optimal (100% agreement rate). No or moderate degree of impairment of daily activities was reported by 93.9% and 73.0% of patients for one and two health-related questions, respectively. The PPV and sensitivity of the questionnaire were 88.97% [confidence interval (CI): 87.58%, 90.22%] and 39.33% (CI: 34.01%, 44.85%), respectively. The OPTA questionnaire showed good agreement regarding health status between physicians and patients and could be used to periodically assess and guide clinical judgment in the management of SIHD in India. Further assessment of the impact of various treatments temporally and in the long term may be warranted.

1000-P: The Economic Impact of Reducing Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers

The purpose of this real-word evidence (RWE) cohort study was to evaluate whether utilization of Cyclical Pressurized Topical Oxygen (TWO2) therapy had any impact on the incidence of Diabetic Foot Ulcer related hospitalizations and amputations over a 12-month period in patients with hard to heal Diabetic foot Ulcers (DFU). An IRB approved retrospective review of deidentified DFU patient medical records was conducted at 2 US Veterans Affairs Medical Centers in Illinois and Virginia, which included demographic information on wound characteristics, clinical characteristics, neuropathy, cardiovascular disease (CVD), peripheral vascular disease (PVD), pain levels and kidney disease etc. Within the unmatched cohorts of the 202 DFU patients (91 TWO2, 111 NO TWO2)there was an 88% reduction in hospitalizations and a 71% reduction in amputations over a 12-month period for the patients treated with TWO2 therapy compared to those that did not receive TWO2 therapy. Propensity score matching was conducted showing similar outcomes and a regression analysis as preformed along with a budget impact model which demonstrated significant cost saving to the payor system. This large RWE study demonstrates the TWO2 therapy positively impacts patients quality of life and the costs associated with treating their DFU by forcing them into remission, resulting in significantly reduced rates of hospitalizations, amputations and cost outlay. Disclosure M.G.Garoufalis: Consultant; Uluru, Employee; AOT Inc., Speaker's Bureau; 3M/KCI, Horizon Therapeutics plc.

405 Understanding patient experience and factors influencing patient preference in the treatment of moderate-to-severe atopic dermatitis through in-depth qualitative patient interviews

Abstract Atopic dermatitis (AD) can enormously affect the lives of patients and their caregivers. Treatments for moderate-to-severe AD include phototherapy, topical and systemic corticosteroids, other immunosuppressive agents and biologic therapies. These treatments offer varied levels of efficacy, safety, response times and modes of administration. Patient preferences for these treatment options and attributes influencing their treatment choice are not well characterized. This qualitative interview-based study evaluated treatment attributes important to adult patients with moderate-to-severe AD providing a basis for a future quantitative discrete choice experiment (DCE). Semi-structured interviews were conducted in adults (≥18 years) recruited via a panel of geographically and demographically diverse patients with AD in the USA. Inclusion required (i) diagnosis of AD for at least one year, (ii) inadequate response to prior topical therapy and (iii) self-reported moderate-to-severe AD or experience with systemic therapy. One-on-one, in-depth 60-min phone interviews were conducted by a trained interviewer in AD real-word evidence studies. Subjects with experience with systemic therapy for AD were queried concerning their involvement in initiating, logistics of and general experience with their most recent systemic treatment. Finally, participants were asked to rate the importance (on a 1–5 scale with 5 being the most important) of 17 attributes that could play a role in their treatment decision-making; these attributes were identified from a targeted literature review and expert dermatologist clinical input. Attributes included treatment efficacy, adverse events and treatment logistics. Interviews are ongoing, and results will be ready and presented in the poster upon acceptance. Findings from the interviews will shed light on recent patient experience with treatments for moderate-to-severe AD and elucidate the treatment attributes that most impact patient treatment preferences. These results will guide the design of a subsequent DCE survey, which will help quantify the relative importance of the treatment attributes identified herein.

Treatment of hypophosphatasia

ypophosphatasia is a systemic metabolic disorder due to genetically determined deficient activity of the tissue non-specific alkaline phosphatase (TNAP). The phenotypic presentation is characterized by a wide spectrum of clinical manifestations regarding both, affected body systems and organs as well as the severity of associated deficits. Appropriate treatment strategies thus have to be multimodal in order to cover individual disease manifestation. For patients with disease onset before adulthood, enzyme replacement therapy with asfotase alfa is approved in Europe to treat the bone manifestations of the disease. Available data from clinical trials as well as real-word evidence confirm encouraging results of this treatment in severely affected children with substantial improvement regarding radiographic and functional outcome parameters as well as overall survival. In adult patients with disease manifestation pursuant to the label, published results also report substantial amelioration of disease-specific deficits along with functional improvements. Meanwhile, there is are also data supporting the safety and efficacy of long-term treatment with asfotase alfa over several years. While inflammatory muskuloskeletal pain - seemingly the most prevalent clinical manifestation along with exhaustion - can transiently be mitigated with on-demand NSARs, essential treatment options to causatively overcome that issue are still lacking. Accordingly, maintenance of musculoskeletal health and functionality requires sustained supportive treatment including physiotherapy and individually adjusted technical orthopedic support. The use and potential clinical impact of phosphate and vitamin B6 on the course of the disease requires further investigation. Current data regarding the use of bone-targeted compounds established for osteoporosis is critical in terms of antiresorptive, while osteoanabolic treatment strategies appear feasible. Considering further organ manifestation including orodental, gastrointestinal and neurological symptoms etc., the entirety of therapeutic measures should be coordinated among a multidisciplinary team and overlooked at an experienced center, while individual tasks can preferably be accomplished at local facilities near the patient’s home.

Sodium polystyrene is unsafe and should not be prescribed for the treatment of hyperkalaemia: primum non nocere!

'Old-generation' potassium (K) binders [i.e. sodium (SPS) and calcium polystyrene sulfonate] are widely used, but with substantial heterogeneity across countries to treat hyperkalaemia (HK). However, there are no randomized data to support their chronic use to manage HK, nor have they been shown to have a renin-angiotensin-aldosterone system inhibitor (RAASi)-enabling effect. These compounds have poor tolerability and an unpredictable onset of action and magnitude of K lowering. Furthermore, SPS may induce fluid overload, owing to the fact that it exchanges K for sodium. Its use has also been associated with colonic necrosis, as emphasized by a black box warning from the US Food and Drug Administration. In contrast, two new K binders, patiromer and sodium zirconium cyclosilicate, have been shown to be safe and well tolerated for chronic management of HK, thereby enabling RAASi optimization, as acknowledged by the latest international cardiorenal guidelines. In view of the lack of reliable evidence regarding the efficacy and safety of the old-generation K binders compared with the placebo-controlled randomized and real-word evidence demonstrating the safety, efficacy and RAASi-enabling effect of the new K binders, clinicians should now use these new K binders to treat HK (primum non nocere!).

Real-world characteristics of patients with sickle cell disease who initiated crizanlizumab therapy

Objective To provide real-word evidence of patients with SCD initiating crizanlizumab, their use of other SCD treatments, and crizanlizumab treatment patterns. Methods Using IQVIA’s US-based, Longitudinal Patient-Centric Pharmacy and Medical Claims Databases patients with a diagnosis of SCD between November 1, 2018, and April 30, 2021, and ≥1 claim for crizanlizumab (date of first claim = index date) between November 1, 2019, and January 31, 2021 who were ≥16 years of age, and had ≥12 months of pre-index data were selected for analysis. Two cohorts were identified based on available follow-up time (3- and 6-month cohorts). Patient characteristics were reported along with pre- and post-index SCD treatments and crizanlizumab treatment patterns (e.g. total doses received, gap-days between doses, days on therapy, discontinuation, and restarts). Results 540 patients met the base inclusion criteria (345 in the 3-month cohort and 262 in the 6-month cohort. Most patients (64%) were female with a mean (SD) age of 35 (12) years overall. Concomitant hydroxyurea use was observed in 19–39% of patients, while concomitant L-glutamine use was observed for 4–8% of patients. 85% of 3-month cohort patients received at least two doses of crizanlizumab, while 66% of the 6-month cohort received at least 4 doses of crizanlizumab. The median number of gap days between doses was 1 or 2. Conclusions 66% of patients who receive crizanlizumab receive at least 4 doses within 6-months. The low median number of gap days suggests high adherence.

Iron therapy and severe arrhythmias in HFrEF: rationale, study design, and baseline results of the RESAFE-HF trial.

The Iron Intravenous Therapy in Reducing the burden of Severe Arrhythmias in HFrEF (RESAFE-HF) registry study aims to provide real-word evidence on the impact of intravenous ferric carboxymaltose (FCM) on the arrhythmic burden of patients with heart failure with reduced ejection fraction (HFrEF), iron deficiency (ID), and implanted cardiac implantable electronic devices (CIEDs). The RESAFE-HF (NCT04974021) study was designed as a prospective, single-centre, and open-label registry study with baseline, 3, 6, and 12month visits. Adult patients with HFrEF and CIEDs scheduled to receive IV FCM as treatment for ID as part of clinical practice were eligible to participate. The primary endpoint is the composite iron-related endpoint of haemoglobin≥12g/dL, ferritin≥50ng/L, and transferrin saturation>20%. Secondary endpoints include unplanned HF-related hospitalizations, ventricular tachyarrhythmias detected by CIEDs and Holter monitors, echocardiographic markers, functional status (VO2 max and 6min walk test), blood biomarkers, and quality of life. In total, 106 patients with a median age of 72years (14.4) were included. The majority were male (84.9%), whereas 92.5% of patients were categorized to New York Heart Association II/III. Patients' arrhythmic burden prior to FCM administration was significant-19 patients (17.9%) received appropriate CIED therapy for termination of ventricular tachyarrhythmia in the preceding 12months, and 75.5% of patients have frequent, repetitive multiform premature ventricular contractions. The RESAFE-HF trial is expected to provide evidence on the effect of treating ID with FCM in HFrEF based on real-world data. Special focus will be given on the arrhythmic burden post-FCM administration.

Improved Outcomes of UM171-Expanded Cord Blood Transplantation Compared with Other Graft Sources: Real World Evidence

Background: Cord blood (CB) transplantation (CBT) has several advantages compared with other graft sources. CBT has low rates of chronic graft-versus-host disease (GVHD) and allows for several human leukocyte antigen (HLA) mismatches, thus expanding donor availability. However, CBT has fallen into disfavor because of its low cell dose and associated prolonged cytopenias, which result in prolonged hospitalization and higher risk of non-relapse mortality (NRM). Furthermore, the need for large CBs leads to selection of poorly HLA matched CBs, further increasing NRM. UM171 is a small molecule that expands hematopoietic stem cells. From 2016 to 2018, 22 patients with high-risk malignancies who lacked a donor were transplanted on a phase I-II clinical trial with a single UM171-expanded CB (Cohen S et al. Lancet Haematol 2019) after a myeloablative conditioning. The goal was to accelerate engraftment while selecting smaller, better HLA matched CBs to decrease NRM while preserving the benefits of CBT. Results demonstrated that indeed UM171-expanded CB has the potential to overcome slow neutrophil engraftment and diminish NRM. The aim of the current analysis was to examine outcomes after conventional single/double ≥ 4/6 HLA-matched CB and 8/8-matched unrelated donor (MUD) peripheral blood stem cell (PBSC) transplantation with UM171-expanded CBT. Methods: Data on UM171-expanded adult CBT recipients were drawn from the phase I-II trial. Data for adult recipients of myeloablative CB and PBSC transplants for hematologic malignancies (acute myeloid and lymphoblastic leukemia, chronic myeloid leukemia, non-Hodgkin and Hodgkin lymphoma) in the United States and Canada during 2014-2019 with a Karnofsky performance status (KPS) score ≥70 were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. CB recipients who received anti-thymocyte globulin or alemtuzumab in the conditioning were excluded from the CIBMTR population. Patients were directly matched for the number of prior allogeneic transplants (alloHCT), refined disease risk index (for 1st alloHCT), disease status (for 2nd alloHCT), and acute myeloid leukemia cytogenetic risk. Patients were matched by propensity score for age, comorbidity index and KPS. CIBMTR attempted to identify 4 controls per UM171 patient. Clinical outcomes included engraftment, NRM, progression-free survival (PFS), overall survival (OS), relapse, GVHD-free, relapse-free survival (GRFS), acute GVHD grade III-IV, and chronic GVHD. PFS, OS, and GRFS were estimated by Kaplan-Meir method; other outcomes were calculated using cumulative incidence estimates; marginal Cox regression models were used for analyzing NRM and GRFS. Results: Overall, 137 CIBMTR (67 CB, 70 PBSC) and 22 UM171-expanded CBT patients participated. Univariate analysis and marginal Cox regression analysis results are shown in Tables 1 and 2, respectively. Median time to neutrophil engraftment was 18 days (range 10-30) for UM171-expanded CB recipients compared to 21 days (range 8-53) for CIBMTR CB recipients (p<0.01) (data not shown). Univariate analysis revealed less 1- and 2-year NRM, improved 2-year PFS, improved 1-year OS, and 1- and 2-year GRFS for UM171-expanded CBT compared to CIBMTR CB controls. The UM171 cases had less 1- and 2-year NRM, improved 2-year PFS, and improved 1- and 2-year GRFS compared to CIBMTR PBSC controls. Furthermore, UM171-expanded CB patients experienced less acute GVHD III-IV and chronic GVHD compared to PBSC recipients. In marginal Cox regression analysis, UM171-expanded CBT recipients were 87% and 63% less likely than CIBMTR CB controls to experience NRM and GRFS events, respectively, and 73% less likely to experience GRFS events than CIBMTR PBSC recipients. Conclusions: This real-word evidence suggests that UM171-expanded CB recipients have select improved outcomes compared to conventional CB and MUD PBSC recipients. While this study was limited by the small number of UM171 CB trial participants and inability to identify the planned number of controls for each case, UM171 expansion of CB appeared to achieve the desired outcome of maintaining CB's benefits while removing its disadvantages. Thus, prospective randomized studies of UM171-expanded CBT compared to MUD PBSC alloHCT are warranted to confirm these results. Study Support: This study was funded by ExCellThera. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Rise of Anti-TNF Biosimilars: Guidelines, Real-World Evidence, and Challenges to Acceptance

The over-production of TNF-α can lead to chronic inflammation and organ damage in immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), axial spondyloarthritis, psoriasis, and inflammatory bowel disease (IBD). Anti-TNF therapy is generally considered to be an effective, well-tolerated treatment option for the management of chronic inflammation in these conditions. Over the past decade, patents for the original reference anti-TNF agents have expired, permitting the development of anti-TNF products that are biologically similar, termed ‘biosimilar’, to the original reference product. Differences in the approval process mean that biosimilars are often available to healthcare services at a considerably lower cost compared with the reference products, providing an opportunity to improve patient access to the benefits of anti-TNF therapy. However, despite the spreading use of biosimilars across healthcare services, some clinicians remain reluctant to prescribe them. The gradual accumulation of long-term data on the real-world use of biosimilars, and an improved understanding of the development and approval process for these products, may help to increase clinicians’ confidence to increase usage of biosimilars. This mini review summarises the current status of anti-TNF biosimilars in clinical practice, including the requirements for regulatory approval, real-word evidence for their equivalence to novel anti-TNFs, guidelines for their use, and challenges to their acceptance by both clinicians and patients.

The Influence of Iron-Deficiency Anaemia (IDA) Therapy on Clinical Outcomes and Healthcare Resource Consumptions in Chronic Kidney Disease Patients Affected by IDA: A Real-Word Evidence Study among the Italian Population.

Anaemia is a uraemia-related complication frequently found in non-dialysis-dependent chronic kidney disease (ND-CKD) patients, with iron-deficiency anaemia (IDA) as the main underlying mechanism. Given the suboptimal anaemia management in ND-CKD patients with a co-diagnosis of IDA, this study evaluated the role of IDA therapy on clinical outcomes and healthcare resource consumptions in an Italian clinical setting. A retrospective observational real-world analysis was performed on administrative databases of healthcare entities, covering around 6.9 million health-assisted individuals. From January 2010 to March 2019, ND-CKD patients were included and diagnosed with IDA in the presence of two low-haemoglobin (Hb) measurements. Patients were divided into IDA-treated and untreated, based on the prescription of iron [Anatomical-Therapeutic Chemical (ATC) code B03A] or anti-anaemia preparations (ATC code B03X), and evaluated during a 6-month follow-up from the index date [first low haemoglobin (Hb) detection]. IDA treatment resulted in significantly decreased incidence of all cause-related, cardiovascular-related, and IDA-related hospitalizations (treated vs. untreated: 44.5% vs. 81.8%, 12.3% vs. 25.3%, and 16.2% vs. 26.2%, respectively, p < 0.001). A healthcare direct cost estimation showed that overall mean expenditure per patient reduced by 47% with IDA treatment (5245€ vs. 9918€, p < 0.001), mainly attributable to hospitalizations (3767€ vs. 8486€, p < 0.001). This real-life analysis on Italian ND-CKD-IDA patients indicates that IDA therapy administration provides significant benefits in terms of patients’ clinical outcomes and healthcare cost savings.