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Fremanezumab is a humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide and is approved in Europe for migraine prevention in adults with ≥4 migraine days/month. The Pan-European Real Life (PEARL) study is a 24-month, prospective, observational study of fremanezumab in chronic or episodic migraine. End points include proportion of patients with ≥50% reduction in monthly migraine days during 6 months of treatment (primary); changes in monthly migraine days, disability scores and acute headache medication use; adherence and persistence; and effectiveness in patients switching from another calcitonin gene-related peptide pathway-targeting monoclonal antibody. PEARL is being conducted in approximately 100 centers in 11 European countries (estimated n = 1100). PEARL will generate important real-world data on effectiveness of fremanezumab and treatment patterns in patients with chronic migraine or episodic migraine.Lay abstract Fremanezumab is an injectable biologic medication that targets calcitonin gene-related peptide, a substance released in the nerves and blood vessels during a migraine attack that plays a role in migraine pain. Fremanezumab is approved in Europe for preventing migraine in adults who experience ≥4 migraine days/month. The Pan-European Real Life (PEARL) study is a 24-month long study that will observe patients with migraine who are starting treatment with fremanezumab in a clinical practice setting under the care of their treating physician. The major goals of the study are to evaluate the effectiveness of fremanezumab for reducing days with migraine attacks in a month, disability associated with migraine and use of acute headache medications to treat migraine, including in patients switching from other biologic migraine therapies in the same drug class. The extent to which patients follow their recommended treatment schedule per their providers’ instructions and whether patients discontinue treatment will also be evaluated. The PEARL study will include1000 patients in 100 centers across 11 European countries. The study will provide important information on effectiveness for patients with migraine receiving fremanezumab in the normal course of their treatment, as well as on patients’ use of fremanezumab according to their prescribing physicians’ recommendations. Trial registration number: EUPAS35111 (European Network of Centres for Pharmacoepidemiology and Pharmacovigilance).

Aim We aimed to compare cardiovascular outcomes of patients with type 2 diabetes (T2D) who initiated GLP-1 receptor agonists (GLP-1RA) or basal insulin (BI) under routine care. Methods We accessed the administrative claims database of the Veneto Region (Italy) to identify new users of GLP-1RA or BI in 2014–2018. Propensity score matching (PSM) was implemented to obtain two cohorts of patients with superimposable characteristics. The primary endpoint was the 3-point major adverse cardiovascular events (3P-MACE). Secondary endpoints included 3P-MACE components, hospitalization for heart failure, revascularizations, and adverse events. Results From a background population of 5,242,201 citizens, 330,193 were identified as having diabetes. PSM produced two very well matched cohorts of 4063 patients each, who initiated GLP-1RA or BI after an average of 2.5 other diabetes drug classes. Patients were 63-year-old and only 15% had a baseline history of cardiovascular disease. During a median follow-up of 24 months in the intention-to-treat analysis, 3P-MACE occurred less frequently in the GLP-1RA cohort (HR versus BI 0.59; 95% CI 0.50–0.71; p Conclusions Patients with T2D who initiated a GLP-1RA experienced far better cardiovascular outcomes than did matched patients who initiated a BI in the same healthcare system. These finding supports prioritization of GLP-1RA as the first injectable regimen for the management of T2D.

PURPOSE IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. METHODS ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of

The Janus kinase inhibitor ruxolitinib is approved for the treatment of myelofibrosis (MF) and improved overall survival (OS) versus control therapy in the phase 3 COMFORT trials. The aim of this retrospective analysis was to examine the real-world impact of ruxolitinib on OS in patients with MF. The US Medicare Fee-for-Service claims database (parts A/B/D) was used to identify patients with ≥ 1 inpatient or ≥ 2 outpatient claims with an MF diagnosis (January 2010–December 2017). Eligible patients with MF were ≥ 65 years old (intermediate-1 or higher risk based on age). Patients were divided into 3 groups based on ruxolitinib approval status at diagnosis and ruxolitinib exposure: (1) preapproval, ruxolitinib-unexposed; (2) post-approval, ruxolitinib-unexposed; and (3) post-approval, ruxolitinib-exposed. In total, 1677 patients with MF were included (preapproval [all ruxolitinib-unexposed], n = 278; post-approval, n = 1399 [ruxolitinib-unexposed, n = 1127; ruxolitinib-exposed, n = 272]). Overall, median age was 78 years, and 39.8% were male. Among patients with valid death dates (preapproval, n = 119 [42.8%]; post-approval, ruxolitinib-unexposed, n = 382 [33.9%]; post-approval ruxolitinib-exposed, n = 54 [19.9%]), 1-year survival rates were 55.6%, 72.5%, and 82.3%, and median OS was 13.2 months, 44.4 months, and not reached, respectively. Risk of mortality was significantly lower post- versus preapproval regardless of exposure to ruxolitinib (ruxolitinib-unexposed: adjusted hazard ratio [HR], 0.67; ruxolitinib-exposed: adjusted HR, 0.36; P P = 0.002). Findings from this study complement clinical data of ruxolitinib in MF by demonstrating a survival benefit in a real-world setting.

Background This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. Methods This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored. Results Overall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level p p p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts. Conclusions The real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study.

Introduction Approximately 30% of patients with a first acute pericarditis episode experience a recurrence ≤ 18 months; ~ 15% experience multiple recurrences. This study assessed the recurrence and economic burden among patients with multiple recurrences. Methods Adults with idiopathic pericarditis were identified in the OptumHealth Care Solutions, Inc., database (2007–2017). Recurrent pericarditis (RP) was defined as ≥ 2 episodes of care separated by > 28 days; multiple recurrences were defined as ≥ 2 recurrences. Results Among 944 patients with RP, 375 (39.7%) experienced multiple recurrences and were propensity score-matched 1:1 to 375 patients without recurrence. Among patients with multiple recurrences, median disease duration (time from first episode to end of last recurrence, confirmed by a 1.5-year recurrence-free period) was 2.84 years. The multiple recurrences cohort had higher rates of hospitalizations per-patient-per-month (PPPM) than the no recurrence cohort (rate ratio [95% confidence interval (CI)] = 2.22 [1.35–3.65]). Mean total healthcare costs were significantly higher in the multiple recurrences versus no recurrence cohort ($2728 vs. $1568 PPPM, cost ratio [95% CI] = 1.74 [1.29–2.32]), mainly driven by higher hospitalization costs in the multiple recurrences cohort (mean: $1180 vs. $420 PPPM, cost ratio [95% CI] = 2.81 [1.80–4.66]). Mean work loss costs were higher in the multiple recurrences versus no recurrence cohort ($696 vs. $169 PPPM, cost ratio [95% CI] = 4.12 [1.64–9.61]). In patients with multiple recurrences, mean cost of the first episode was $19,189; subsequent recurrences ranged from $2089 to $7366 (second recurrence = $6222). Conclusion In conclusion, among patients with multiple pericarditis recurrences, disease symptoms persisted several years, and healthcare and work loss costs were further compounded in this subset of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01868-7.

Apremilast, an oral phosphodiesterase-4 inhibitor, is approved for use in the management of psoriasis and psoriatic arthritis. Although its efficacy and safety have been well established in clinical studies, in real-world settings, different practice scenarios have been reported. This review paper serves to evaluate clinical real-world scenarios and aspects of treatment for which the information in the literature was considered to be lacking or controversial. Following a literature review, a panel of five dermatologists with expertise in psoriasis considered five scenarios; namely, the positioning of apremilast in psoriasis, its use in difficult-to-treat areas, special conditions and populations, safety, dose titration and dose in maintenance therapy. These were then assessed with psoriasis experts in India using a web-based questionnaire. A total of 28 questions were discussed regarding these scenarios. According to the responses, apremilast is effective in stable mild to moderate psoriasis as monotherapy and in severe psoriasis in combination. Also, a positive response was received with regard to its effectiveness in difficult locations such as the scalp, palms and soles. To reduce adverse effects, prolonged titration therapy over 4 weeks is required and lower doses can be prescribed to maintain remission. Apremilast therapy should be continued for a minimum of 8 weeks once initiated to achieve the desired results, and the total duration of therapy should be about 24 weeks for better efficacy. It is also effective in many other cases, such as obese patients, patients with hepatitis B or C and HIV, or patients on polypharmacy. It was also reported that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. Overall, apremilast is an attractive option for the individualized treatment of psoriasis owing to its favorable safety profile, its ease of oral administration without the need for screening or ongoing laboratory monitoring, and its positive impact on symptoms and lesions in difficult-to-treat areas.

Min Seok Kim,1 Jasmine Choi,2 Hyeong Du Lee,3 Se Joon Woo1 On behalf of the Korea Ozurdex Post-Marketing Surveillance Study Group1Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Allergan, an AbbVie Company, Irvine, CA, USA; 3Allergan, an AbbVie Company, Seoul, KoreaCorrespondence: Se Joon WooDepartment of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of KoreaTel +82-31-787-7377Fax +82-31-787-4057Email sejoon1@snu.ac.krPurpose: To supplement established efficacy and safety data, this analysis evaluated the real-world use of dexamethasone (DEX) intravitreal implant 700 μg for retinal vein occlusion (RVO)-related macular edema in an Asian population and baseline factors potentially associated with DEX implant efficacy.Patients and Methods: A prospective, observational, post-marketing surveillance study was conducted at 38 sites in South Korea in patients consecutively presenting with macular edema following branch or central RVO (BRVO, CRVO), and administered a first DEX implant. Follow-up visits and subsequent DEX or other therapies conformed with local practice. Outcome measures included best-corrected visual acuity (BCVA), change in BCVA from baseline, responder rates, and adverse events. Associations between baseline characteristics and BCVA gains were evaluated. Month-1, -2, -4, and -6 visit analysis windows were established.Results: In all, 700 patients (79.1% BRVO, 20.9% CRVO) received 1.12 DEX implants (mean) and were followed for 101.5 days (standard deviation, 51.7); 90% received a single implant. Among patients with analyzable data, mean BCVA improved from baseline with peak changes in Month 2 of − 0.193 and − 0.212 LogMAR, (P < 0.0001) and remained significant in the BRVO subgroup at the Month 4 and 6 windows (P < 0.0001 and P = 0.0039, respectively). Treatment-naïve patients experienced greater BCVA increases. The proportion of patients with stable/improved BCVA tended to decrease after Month 2 through Month 6 and the decline was greater in the CRVO subgroup. At the Month-2 window, ≥ 1-, 2- and 3-line increases were positively associated with younger age, worse baseline BCVA, and treatment naivety. The most common adverse event was increased intraocular pressure.Conclusion: In the real-world clinical setting in South Korea, DEX implant improved visual acuity and had a favorable safety profile similar to that reported in randomized controlled trials and observational European and North American studies. These data further support the value of DEX implant as a treatment option for RVO.ClinicalTrials.gov Identifier: NCT01976650. Date of registration: November 6, 2013.Keywords: retinal vein occlusion, dexamethasone, intravitreal, implant, post-marketing, real world

Introduction Patients with atopic dermatitis (AD) experience burdensome symptoms and impaired quality of life (QoL). The objective of this study was to investigate the effects of topical AD therapies on disease control, physician and patient treatment satisfaction, and QoL in a real-world setting. Methods This was a retrospective, point-in-time study of physician-completed medical records and patient surveys drawn from two Adelphi AD Disease Specific Programmes™ (1. adults ≥ 18 years old; 2. pediatrics ≤ 17 years old) in the USA. Eligible physicians completed patient record forms and provided disease control assessments. Physicians and matched patients were surveyed regarding their satisfaction with current treatment. Patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Children’s DLQI (CDLQI), Patient-Oriented Eczema Measure (POEM), and the Work Productivity and Activity Impairment (WPAI) questionnaire. Results A total of 394 adult (topicals only, n = 284; topical plus systemic, n = 110) and 144 adolescent (aged 12–17 years; topicals only, n = 114; topical plus systemic, n = 30) patients who had received their current treatment for at least 1 month were included. Overall, 24.5% of patients had physician-reported uncontrolled disease (adults, 22.8%; adolescents, 29.2%). Rates of physician- and patient-reported dissatisfaction with current treatment were 32.0% (adults, 28.2%; adolescents, 42.4%) and 24.8% (adults, 24.0%; adolescents, 26.8%), respectively, and were higher for patients with uncontrolled versus controlled disease. Poorer disease control and higher rates of treatment dissatisfaction were generally reported among patients receiving topical plus systemic therapy versus topicals alone. Patients with uncontrolled versus controlled disease reported more impairment in the DLQI, CDLQI, POEM, and WPAI (P, Plain Language Summary Atopic dermatitis (or eczema) is a common skin condition that causes dry, cracked, and itchy skin. Patients are frequently prescribed topical therapy, such as ointments and creams, to apply directly to the affected skin. Additionally, patients may be prescribed systemic therapies, which are oral or injectable medications that work throughout the entire body. This study included 394 adults and 144 adolescents (aged 12–17 years) with atopic dermatitis. All patients in the study were receiving topical therapy, and some received both topical and systemic therapy. The goal of the study was to evaluate how satisfied patients and their doctors were with current treatment and to learn how patients in the study felt about their quality of life. Patients and their doctors completed surveys that asked about feelings, symptoms, and whether their condition affects their work. The study results showed that patients had high levels of dissatisfaction with their treatment. Doctors reported that between one-fifth and one-quarter of adult patients and up to one-half of adolescent patients had uncontrolled disease (defined as changeable or worsening). Patients with uncontrolled disease reported higher dissatisfaction with their therapy and a negative outlook on their quality of life versus those with controlled disease (defined as stable or improving by their doctors). In summary, doctors and their patients currently using topical medications to treat atopic dermatitis reported that treatments were not working well enough and that uncontrolled disease was negatively affecting patients’ quality of life and work, indicating that additional treatment options are needed.

This paper aims to summarize through meta-analyses the overall vaccine effectiveness of the BNT162b2 mRNA vaccine from observational studies. A systematic literature search with no language restriction was performed in electronic databases to identify eligible observational studies which reported the adjusted effectiveness of the BNT162b2 mRNA vaccine to prevent RT-PCR confirmed COVID-19. Meta-analyses with the random-effects model were used to calculate the pooled hazard ratio (HR) and pooled incidence rate ratio (IRR) at 95% confidence intervals, and the vaccine effectiveness was indicated as (pooled HR − 1)/HR or (pooled IRR − 1)/IRR. Nineteen studies were included for this meta-analysis. The meta-analysis revealed significant protective effect against RT-PCR confirmed COVID-19 ≥ 14 days after the first dose, with vaccine effectiveness of 53% (95% confidence interval 32–68%), and ≥ 7 days after the second dose, with vaccine effectiveness of 95% (95% confidence interval: 96–97%). Despite its effectiveness, reporting vaccine safety data by relevant stakeholders should be encouraged as BNT162b2 mRNA is a new vaccine that has not gained full approval. There have been limited data about vaccine effectiveness among immunocompromised patients; thus, the vaccine should be used cautiously in this patient population.

Background Limited real-world data exist on healthcare resource utilization (HCRU) and associated costs of patients with heart failure (HF) with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), including urgent HF visits, which are assumed to be less burdensome than HF hospitalizations (hHFs)Hypothesis This study aimed to quantify the economic burden of HFrEF and HFpEF, via a retrospective, longitudinal cohort study, using IBM(R) linked claims/electronic health records (Commercial and Medicare Supplemental data only).Methods Adult patients, indexed on HF diagnosis (ICD-10-CM: I50.x) from July 2012 through June 2018, with 6-month minimum baseline period and varying follow-up, were classified as HFrEF (I50.2x) or HFpEF (I50.3x) according to last-observed EF-specific diagnosis. HCRU/costs were assessed during follow-up.Results About 109 721 HF patients (22% HFrEF, 31% HFpEF, 47% unclassified EF; median 18 months' follow-up) were identified. There were 3.2 all-cause outpatient visits per patient-month (HFrEF, 3.3; HFpEF, 3.6); 69% of patients required inpatient stays (HFrEF, 80%; HFpEF, 78%). Overall, 11% of patients experienced hHFs (HFrEF, 23%; HFpEF, 16%), 9% experienced urgent HF visits (HFrEF, 15%; HFpEF, 12%); 26% were hospitalized less than 30 days after first urgent HF visit versus 11% after first hHF. Mean monthly total direct healthcare cost per patient was $9290 (HFrEF, $11 053; HFpEF, $7482).Conclusions HF-related HCRU is substantial among contemporary real-world HF patients in US Commercial or Medicare supplemental health plans. Patients managed in urgent HF settings were over twice as likely to be hospitalized within 30 days versus those initially hospitalized, suggesting urgent HF visits are important clinical events and quality improvement targets.

Background Interventional studies are the fundamental method for obtaining answers to clinical questions. However, these studies are sometimes difficult to conduct because of insufficient financial or human resources or the rarity of the disease in question. One means of addressing these issues is to conduct a non-interventional observational study using electronic health record (EHR) databases as the data source, although how best to evaluate the suitability of an EHR database when planning a study remains to be clarified. The aim of the present study is to identify and characterize the data sources that have been used for conducting non-interventional observational studies in Japan and propose a flow diagram to help researchers determine the most appropriate EHR database for their study goals. Methods We compiled a list of published articles reporting observational studies conducted in Japan by searching PubMed for relevant articles published in the last 3 years and by searching database providers’ publication lists related to studies using their databases. For each article, we reviewed the abstract and/or full text to obtain information about data source, target disease or therapeutic area, number of patients, and study design (prospective or retrospective). We then characterized the identified EHR databases. Results In Japan, non-interventional observational studies have been mostly conducted using data stored locally at individual medical institutions (663/1511) or collected from several collaborating medical institutions (315/1511). Whereas the studies conducted with large-scale integrated databases (330/1511) were mostly retrospective (73.6%), 27.5% of the single-center studies, 47.6% of the multi-center studies, and 73.7% of the post-marketing surveillance studies, identified in the present study, were conducted prospectively. We used our findings to develop an assessment flow diagram to assist researchers in evaluating and choosing the most suitable EHR database for their study goals. Conclusions Our analysis revealed that the non-interventional observational studies were conducted using data stored local at individual medical institutions or collected from collaborating medical institutions in Japan. Disease registries, disease databases, and large-scale databases would enable researchers to conduct studies with large sample sizes to provide robust data from which strong inferences could be drawn.

Purpose: To report the one and two year outcome of cycles of three, monthly anti-VEGF injections given upon reactivation of the disease in eyes with neovascular age-related macular degeneration (nAMD). Methods: Retrospective study of naïve nAMD cases with more than one year of follow-up, treated with a protocol of cycles of three monthly injections of anti-VEGF drugs upon reactivation. Visual acuity (VA) and central macular thickness (CMT) are the main outcome measures. Results: Twenty-six patients with a mean age of 78.15 ± 9.29 years (57.7% female) were included. The mean follow-up was 30.89 ± 6.95 months. Treatment started with bevacizumab in all patients but in six patients was switched to aflibercept due to inadequate response to intravitreal bevacizumab injection. The mean VA at baseline and at 12 and 24 months was 53.87 ± 21.84, 60.54 ± 21.13, and 53.68 ± 27.16 ETDRS letters, respectively. Patients gained a mean of 6.67 ± 13.7 (p = 0.013, 95% CI= 0.60 to 12.65) and 0.77 ± 15.21 (p = 0.4, 95% CI: –5.65 to 7.2) letters at 12 and 24 months. CMT at baseline, 12, and 24 months was 403.55 ± 147.59, 323.95 ± 79.58, and 298.59 ± 77.161 µm, respectively. The number of injections in the first and second years were 7.65 ± 2.64 and 5.52 ± 3.01, respectively. Three eyes (12.5%) lost > 15 letters at 24 months. Conclusion: This protocol can stabilize or improve vision in 87.5% of nAMD patients and can reduce the number of visits.

Leah B Sansbury,1 Chanchal Bains,2 David A Lipson,3,4 Afisi S Ismaila,5,6 Sarah H Landis5 1Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK; 3Clinical Sciences, GlaxoSmithKline, Collegeville, PA, USA; 4Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 5Value Evidence and Outcomes, GlaxoSmithKline, Collegeville, PA, USA; 6Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Leah B SansburyValue Evidence and Outcomes, GlaxoSmithKline, Building 5, 42 Moore Drive, Research Triangle Park, NC, 27709, USATel +1 919 812 0719Email leah.b.sansbury@gsk.comIntroduction: Until recently, triple therapy for chronic obstructive pulmonary disease (COPD) has only been available through treatment with multiple inhalers. Evidence on real-world use of multiple-inhaler triple therapy (MITT), including duration of use and treatment patterns, is limited.Methods: A retrospective, observational study of electronic health records and hospital episodes in patients with COPD initiating MITT between 2013 and 2015 in the UK was performed. This study described patients initiating, treatment persistence and discontinuation, and prior and subsequent COPD treatments.Results: Eligible patients (N=3825) had a mean age of 69.5 years; most were former or current smokers (95%). The majority (86%) initiated MITT with two inhalers and 14% initiated with three inhalers. Mean duration of use was 5.1 (standard deviation: 4.6) months; 24% of patients persisted for 12 months. Patients who had significantly poorer lung function at baseline (12 months prior to initiating MITT) and had experienced significantly more moderate-to-severe acute exacerbation of COPD (AECOPD) and hospitalizations during the baseline period were more likely to persist for 12 months, compared with those who discontinued within 12 months. Most patients stepped down to an inhaled corticosteroid/long-acting β2-agonist combination (ICS/LABA; 48%) or a long-acting muscarinic antagonist (LAMA; 45%) after discontinuing MITT.Conclusion: Initiation of MITT occurred in patients with clinically relevant symptoms and a history of AECOPD. Persistence varied and was most likely linked to disease severity, although more research is required to fully understand why patients discontinue MITT, the subsequent clinical consequences of therapy discontinuation, and the potential impact of newly available single-inhaler triple therapies.Keywords: chronic obstructive pulmonary disease, COPD, multiple-inhaler triple therapy, MITT, general practice, real world, treatment patterns

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice. The mean (SD) age was 75.6 (6.7) years; 152 (47.4%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 2-4, and 73 (25.1%) had high cytogenetic risk. The most frequent frontline therapy was non-VMP bortezomib-based regimens (n=207; 30.7%), which were more frequent among patients with ECOG PS 0/1 and higher risk (e.g., international staging system (ISS) stage III, severely impaired glomerular filtrate rate (GFR), high lactate dehydrogenase (LDH), and high-risk cytogenetics); 185 patients (27.4%) started an attenuated (lite) VMP regimen, and 159 (23.6%) a VMP (VISTA) regimen. Median progression-free survival and overall survival (OS) were 15.3 months (95%CI 14.0-16.9) and 33.5 months (95%CI 29.1-37.2), respectively; 405 patients (78.2%) achieved partial response or better. Age, ECOG PS, ISS stage, serum LDH, GFR, cytogenetic risk, and treatment regimen significantly influenced OS. In this study, a remarkable proportion of transplant-ineligible patients with MM were older, frontline regimens were highly heterogeneous, and patients at higher risk often received less efficacious combinations. These findings suggest that clinicians have limited objective criteria for therapeutic decisions for this patient group.

Introduction The effectiveness of telmisartan has been reported in Indian clinical trials; however, real-world data are limited. We aimed to provide real-world evidence regarding the effectiveness of telmisartan as monotherapy or in combination with other antihypertensive drugs (AHDs) in Indian patients with essential hypertension. Methods Electronic medical record data of adult patients diagnosed with essential hypertension (≥ 140/90 mmHg) and who were prescribed telmisartan as mono- or add-on therapy were retrospectively analyzed. Patients were classified according to the number of AHD classes prescribed on initiating telmisartan. Change in systolic and diastolic blood pressure (SBP and DBP) after a month of treatment and the proportion of patients who achieved treatment goals according to the 2018 European Society of Cardiology/European Society of Hypertension guidelines were evaluated. Results A majority (90.6%) of the 1304 patients included in the study were on telmisartan monotherapy or telmisartan + 1 AHD. The mean (95% confidence interval [CI]) change in the telmisartan monotherapy group was SBP (−13.3 [−14.6, −12.0] mmHg) and DBP (−7.2 [−7.9, −6.5] mmHg), and the mean (95% CI) change in the telmisartan + 1 AHD group was SBP (−10.8 [−13.1, −8.5] mmHg) and DBP (−6.5 [−7.7, −5.3] mmHg) (P

Background/aims Direct‐acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)‐infected patients. The real‐world treatment outcome in Taiwanese patients on a nationwide basis is elusive. Methods The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end‐of‐treatment). Results A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype‐1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment‐naïve noncirrhotic, treatment‐naïve cirrhotic, treatment‐experienced noncirrhotic and treatment‐experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment‐experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment‐naïve noncirrhotic patients (94.8%) and treatment‐experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence

Robert S Epstein,1 Upal K Basu Roy,2 Matti Aapro,3 Tehseen Salimi,4 Donald Moran,4 JoAnn Krenitsky,1 Megan L Leone-Perkins,5 Cynthia Girman,6 Courtney Schlusser,7 Jeffrey Crawford8 1Epstein Health, LLC., Woodcliff Lake, NJ, USA; 2LUNGevity Foundation, Bethesda, MD, USA; 3Clinique De Genolier, Genolier, Switzerland; 4G1 Therapeutics Ltd., Research Triangle Park, NC, USA; 5HealthiVibe, a Division of Corrona, LLC., Arlington, VA, USA; 6Chapel Hill Consulting, LLC., Chapel Hill, NC, USA; 7UNC Gillings School of Global Public Health, Chapel Hill, NC, USA; 8Duke University Medical Center, Durham, NC, USACorrespondence: Robert S EpsteinEpstein Health, LLC., Woodcliff Lake, NJ, 07677, USATel +1 201-285-5800Email repstein@epsteinhealth.comPurpose: To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the “patient voice” describing how CIM impacts their daily lives.Participants and Methods: Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥ 1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: “In your own words, please describe how side effects from myelosuppression have impacted your life.”Results: Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1– 10 scale of “bothersomeness”). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24– 43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family.Conclusion: Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.Keywords: cancer, chemotherapy, myelosuppression, real world, quality of life, patient burden

Francesco Menzella,1 Marco Bonavia,2 Matteo Bonini,3 Maria D’Amato,4 Salvatore Lombardo,5 Nicola Murgia,6 Vincenzo Patella,7,8 Massimo Triggiani,9 Girolamo Pelaia10 1Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, Italy; 2Pneumologia Riabilitativa - Ospedale Ge-Arenzano, ASL3-, Genoa, Italy; 3Department of Cardiovascular and Thoracic Sciences, Università Cattolica del Sacro Cuore, Rome, Italy; 4Respiratory Department- Monaldi Hospital AO Dei Colli, Naples, Italy; 5Pneumology Unit, Ospedale Giovanni Paolo II, Lamezia Terme, Italy; 6Section of Occupational Medicine, Respiratory Diseases and Toxicology, University of Perugia, Perugia, Italy; 7Division of Allergy and Clinical Immunology, Department of Medicine ASL Salerno, Santa Maria Della Speranza Hospital, Salerno, Italy; 8Postgraduate Program in Allergy and Clinical Immunology, University of Naples Federico II, Naples, Italy; 9Division of Allergy and Clinical Immunology, University of Salerno, Fisciano, Italy; 10Department of Health Sciences, Respiratory Unit, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyCorrespondence: Francesco MenzellaPneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS, Reggio Emilia, ItalyTel +390522296073Email Francesco.Menzella@ausl.re.itPurpose: Severe eosinophilic asthma (SEA) is characterized by high eosinophilia, severe symptoms, important comorbidities, frequent exacerbations, and poor asthma control. Benralizumab, targeting the interleukin-5 receptor alpha, proved effective in inducing rapid eosinophil depletion and amelioration of symptoms and lung function; it also allowed to reduce exacerbations and the use of oral corticosteroids (OCS). The present case series, spanning different subtypes of SEA, aimed at expanding the real-world experience with benralizumab in Italy.Patients and Methods: We collected data from SEA patients treated with benralizumab, at baseline and during treatment. We focused on the effects of benralizumab in the following conditions and endpoints: i) overlap between high-IgE and high-eosinophilic asthma; ii) presence of nasal polyposis as comorbidity; iii) corticosteroid-sparing effect; iv) patient perception.Results: Ten SEA patients (females: N=7; age range: 19– 70 years) referred to 8 Italian Centers and treated with benralizumab were included, presenting with several comorbidities such as non-allergic disease (8/10), atopy (3/10), high IgE (5/10) and nasal polyposis (6/10). Overall, benralizumab yielded optimal disease control in all patients, particularly in terms of rapid clinical and functional improvement, decreased systemic steroid need (OCS therapy was completely discontinued in 7 cases) and amelioration of patient quality of life, except for 1 case, in whom other conditions not related to benralizumab therapy interfered with the patient perception.Conclusion: Our findings further support the efficacy and safety of benralizumab observed in randomized clinical trials, providing even better results for lung function improvement.Keywords: benralizumab, IL-5 receptor, oral corticosteroids, overlap IgE/eosinophilic asthma, polyposis, real world, severe eosinophilic asthma

Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Mantle cell lymphoma (MCL) accounts for approximately 3% of all cases of malignant lymphoma in Japan. The CLIMBER-DBR (Treatment practices and patient burden in chronic lymphocytic leukemia and mantle cell lymphoma patients in the real world: An observational database research in Japan) study examined the clinical characteristics, treatment patterns, and healthcare resource utilization of MCL in a real-world clinical setting in Japan. Using the Japanese Medical Data Vision database, we extracted data for 1130 patients with MCL (ICD-10 code C83.1) registered between March 1, 2013 and February 28, 2018. The date of first MCL diagnosis was taken as the index date. The mean (standard deviation) age, body weight, and modified Charlson Comorbidity Index were 71.4 (10.9) years, 58.3 (11.7) kg, and 1.9 (1.6), respectively, and 24.6% were ≤65 years old. The median follow-up period was 654 days (first-third quartile 290.5 E049 days). A total of 802 patients (71.0%) underwent first-line treatment. The most common first-line treatment was bendamustine/rituximab (BR; 27.8%), followed by rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP; 15.6%) and rituximab/tetrahydropyranyl-adriamycin/cyclophosphamide/vincristine/prednisolone (R-THP-COP; 6.5%). The median (95% confidence interval) times to initial (first-line), second-line, and third-line treatments were 45 (36 E2), 687 (624 E34), and 1188 (1099 E444) days, respectively. Treatment practices for MCL in Japan are consistent with trends observed in Western countries. Our study can serve as a benchmark to assess future MCL treatments in Japan.

Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes. Regulatory B cells (Bregs) were observed to be involved into specific defects in MM. Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs. We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3rd agent, were enrolled from 2017. Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow. The correlation between Bregs and clinical characters were further analyzed. This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM. The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here. This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM. Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.

Purpose Effectiveness of ocriplasmin for vitreomacular traction (VMT) varies depending on the presence of common ocular conditions and patient selection criteria. We carried out a systematic literature review and meta‐analysis of ocriplasmin studies conducted in real‐world settings (RWS) and compared outcomes with those from randomized controlled trials (RCTs). Methods We included prospective and retrospective studies from RWS documenting effectiveness of ocriplasmin in patients with VMT with or without MH, and RCTs of ocriplasmin versus control. Key end‐points were vitreomacular adhesion resolution (VMAR), nonsurgical MH closure, need for vitrectomy and safety. We conducted meta‐regression on pooled results to evaluate effects of baseline covariates and study design on outcomes. Results Thirty RWS (2402 patients) and 5 RCTs (737 patients) were included epiretinal membrane (ERM) and broad VMA were more prevalent in RCTs. Primary VMAR, vitrectomy and MH closure rates were comparable between RWS and RCTs. Rates of nsVMAR were significantly higher in RWS than RCTs (odds ratio 1.66; 95% confidence interval [CI]: 1.18–2.34). nsVMAR rates were inversely associated with ERM prevalence (odds ratio 0.20; 95% CI: 0.08–0.51). Compared with the recent OASIS trial, RWS reported a higher incidence of new/worsening subretinal fluid cases and less photophobia, photopsia, vitreous floaters, electroretinogram abnormalities and MH progression. Conclusions Ocriplasmin was significantly more effective in achieving nsVMAR in RWS than in RCTs. Lower ERM prevalence in RWS was the single significant explanatory variable for this difference. Conclusions on ocriplasmin safety in RWS are limited due to inconsistent reporting.

Objective : Several evidence-based practice guidelines have been developed to better treat bipolar disorder. However, the articles cited in these guidelines were based on clinical or basic studies with specific conditional settings and were not sufficiently based on real-world clinical practice. In particular, there was little information on the doses of mood stabilizers. Methods The MUlticenter treatment SUrvey on BIpolar disorder in Japanese psychiatric clinics (MUSUBI) is a study conducted to accumulate evidence on the real-world practical treatment of bipolar disorder. The questionnaire included patient characteristics such as comorbidities, mental status, treatment period, Global Assessment of Functioning (GAF) score, and details of pharmacological treatment. Results Most patients received mood stabilizers such as lithium (n = 1,317), valproic acid (n = 808), carbamazepine (n = 136), and lamotrigine (n = 665). The dose of lithium was correlated with age, body weight, number of episodes, depression and GAF. The dose of valproic acid was correlated with body weight, number of episodes, presence of a rapid cycle and GAF. The dose of carbamazepine was correlated with age, mania, and the presence of a rapid cycle. The dose of lamotrigine was correlated with the number of episodes, depression, mania, psychotic features, and the presence of a rapid cycle. Doses of coadministered mood stabilizers were significantly correlated, except for the combination of valproic acid and lamotrigine. Conclusion The dose of mood stabilizers was selectively administered based on several factors, such as age, body composition, current mood status and functioning. Further prospective studies are required to confirm these findings.

Aims The aims of this study were to evaluate if the risk of cardiovascular events and all‐cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin–angiotensin–aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all‐cause mortality among HK patients with non‐optimal adherence to RAASi therapy. Methods and results In this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3 months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was ≥5.5 mmol/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A, has been available for the treatment of moderate to severe psoriasis and psoriatic arthritis since February 2015 in Japan. Because there was a time gap after the previous approval of biologics for psoriatic disease indication, it was suggested that patients to be treated with secukinumab at its launch might have refractory disease symptoms. In order to assess the safety and effectiveness of secukinumab in those patients, a 52‐week, open‐label, multicenter, observational cohort study was conducted. In total, 306 and 250 patients were included in the safety and effectiveness analysis sets, respectively. Over half of patients had previously received biologics (56.9%). Adverse events, serious adverse events and adverse reactions were reported in 41.2%, 7.2% and 24.2% of patients, respectively. The most commonly reported adverse reactions were oral candidiasis (2.9%), consistent with those reported in clinical studies. In addition, none of the patient characteristics assessed for the effect on safety of secukinumab increased the occurrence of adverse reactions. Psoriasis Area and Severity Index score (mean ± standard deviation) improved from baseline (14.7 ± 12.3) to week 12 (1.78 ± 3.3), which was maintained up to week 24 (1.59 ± 3.0). The proportion of patients with a Dermatology Life Quality Index score of 0/1 improved from baseline (2.2%) to week 12 (64.7%) and sustained up to week 24 (71.4%). In addition to the skin symptoms, improvement was observed in all psoriatic arthritis disease‐related assessments. The current study reaffirmed the safety and effectiveness of secukinumab with broader patients than those in the clinical studies.

Purpose: To analyse and compare the number and interval of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), as well as the visual development in patients followed up for one to three years in clinical practice and during different index periods. Methods: This observational study included treatment-naive eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017, stratified by different index periods (2007–2010, 2011–2013, 2014–2015 and 2016–2017) and by follow-up cohorts for each index period of one, two or three years (cohorts 1–3). Their intravitreal anti-VEGF treatment was assessed by number of injections, injection intervals, visual acuity (VA) and near VA change. Results: From the earliest index period 2007–2010 to the latest 2016–2017, the number of injections increased for the comparable follow-up time; 6.2 ± 1.4 versus 8.3 ± 2.0 injections after 1 year of treatment, 4.8 ± 1.6 versus 6.7 ± 2.4 during year 2. The last injection interval was 73 ± 34 days after 1, 71 ± 33 after 2 and 67 ± 32 after 3 years of follow-up for the index period 2014–2015. For the same period, the percentage of eyes with at least two consecutive 12–16 weeks of injection interval over 1-, 2- and 3-year follow-up increased from 5.2%, 15.0%, to 17.5% respectively. Baseline VA for eyes indexed 2016–2017 increased and presented with 62.1 ± 13.4 letters compared with 57.7 ± 13.5 letters in 2007–2010; p < 0.0001. Conclusions: From the earliest to the latest index periods, the number of injections increased for the comparable follow-up time. Accordingly, baseline VA and near VA and their outcomes improved continuously. (Less)

Background Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2‐positive early‐stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population‐based cohort investigation aimed to assess both the short‐ and long‐term cardiovascular (CV) outcomes in women with early breast cancer treated with T‐based or standard adjuvant chemotherapy (CT). Materials and Methods We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first‐line adjuvant T‐based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short‐ and long‐term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow‐up. Results Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow‐up of 5.88 years, short‐ and long‐term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6–8.0) for short‐term and 1.2 (95% CI, 0.9–1.6) for long‐term CV risk. Discussion In our large real‐world investigation, T‐associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long‐term worsening of CV events. Implications for Practice Adjuvant trastuzumab‐based chemotherapy represents the backbone therapy in patients with HER2‐positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment‐related toxicities. In this wide multicenter and unselected cohort, long‐term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed., With breast cancer patients experiencing longer survival, emphasizing their overall health through management of late and long‐term treatment effects is becoming increasingly important. This article reports a multiregional real‐world population‐based cohort investigation carried out to compare short‐term and long‐term cardiovascular risk of symptomatic cardiovascular events in women with localized breast cancer treated with trastuzumab‐based or standard adjuvant therapy in clinical practice.

Purpose The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on the society and individuals. Based on thyroid cancer data from patients treated in Liaocheng People's Hospital in 2017, with Chinese national and regional characteristics, in this study we addressed the controversy of which initial thyroid surgical mode, lobectomy, or total thyroidectomy is the most effective. Patients and methods Clinical and pathological data from 552 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, 40 patients underwent endoscopic surgery, with resection, including lobectomy + central lymph node dissection of the affected lobe, while 512 cases underwent total thyroidectomy + central lymph node dissection. Results The metastasis rate for all patients was 59.42%, with lymph node metastasis of papillary thyroid microcarcinoma of 46.92%; however, for patients with tumors >2 cm, the proportion developing metastasis was increased to 77.53%. Conclusion In thyroid cancer, rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. Our data suggest that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, at least in tumors larger than 1 cm, to avoid the risks associated with secondary surgery and effects on patient quality of life.

Background/objective: Observational clinical data from cladribine-treated patients with relapsing forms of multiple sclerosis (MS) were recorded in the Australian MS registry powered by the MSBase registry platform (5-year follow-up) and analysed to complement information from the pivotal cladribine clinical trials in MS. Methods: A cohort of 90 cladribine-treated patients with follow-up data reported by treating physicians and recorded in the Australian MSBase registry (database lock February 2016) were examined. Clinical data included Expanded Disability Status Scale (EDSS) scores, relapses and other disease-modifying drugs (DMDs) administered before and after cladribine treatment. Results: Mean age on starting cladribine was 47 years; mean age at MS onset was 34 years, and median baseline EDSS score was 5.25. Disability trajectories in patients with sufficient follow-up suggested an overall increasing trend prior to cladribine treatment which was reduced during the 2-year post-treatment. Approximately 80% of patients were EDSS progression-free, 65% remained relapse-free after 2 years and median time to next DMD was 1.7 years. Conclusion: These observational data suggest a disease-modifying effect in this cohort of relapsing MS patients characterised by older and more disabled patients. Since these data represent a single-arm cohort, clinical trials and larger comparative post-marketing studies are needed to validate and extend these findings.

Introduction Data are lacking on severe asthma burden in elderly people in Japan. We assessed the prevalence and clinical/economic burden of severe asthma and asthma-related hospitalizations in elderly and younger Japanese patients. Methods This retrospective study analyzed outpatient claims data and inpatient hospital discharge records among patients aged ≥ 15 years with asthma (defined as ≥ 2 prescriptions of inhaled corticosteroids [ICS] or ICS/long-acting beta-agonists [LABA]) between 1 July 2014 and 30 June 2017. We analyzed the outpatient visit assessment population with severe asthma (≥ 240-day prescription of high-dose ICS and ≥ 90-day prescription of ≥ 1 additional controllers) and the asthma-related hospitalization population (≥ 1 hospital admission[S] with a primary diagnosis of asthma/status asthmaticus and use of systemic corticosteroids) over a 1-year observation period before the date of each patient’s latest asthma prescription or asthma-related hospitalization within the study period. The primary outcome was the proportion of elderly (≥ 65 years) and younger (15–39 and 40–64 years) patients among the outpatient visit assessment population. Secondary outcomes included outpatient and inpatient characteristics, asthma-related healthcare resource utilization, and asthma-associated costs, by age group. Results Of the outpatient visit assessment population (n = 35,742), 4211 had severe asthma, with the prevalence of 8.2%, 12.8%, and 12.4% for the 15–39, 40–64, and ≥ 65 years age groups, respectively. Elderly versus younger outpatients with severe asthma had higher cumulative oral corticosteroid doses. Among both outpatient visit assessment population and hospitalization assessment population, elderly versus younger outpatients with severe asthma or asthma-related hospitalizations had more comorbidities, required more biological, hematological, immunological, and microbiological tests, and incurred higher asthma-associated costs. Conclusions In addition to reaffirming the higher prevalence of severe asthma in Japanese patients ≥ 40 years versus those

Background Glaucoma treatments are mostly presented in uni-dose or multi-dose format. A certain number of patients with visual acuity and dexterity problems may have problems in instilling eye drops. Aim To assess patient satisfaction and ease of use of a preservative-free glaucoma treatment (dorzolamide/timolol) in a new and innovative patented multi-dose delivery system. Methods Retrospective, international, multicentre, non-interventional study in 788 adult patients using a multi-dose delivery system for at least 28 days. Results Mean patient age was 68.1 ± 12.1 years. Mean duration of multi-dose delivery system use was 132.1 ± 125.1 days; 66.5% of the patients previously used multi-dose and 33.5% uni-dose delivery systems (n = 734); 78.3% of the patients were satisfied or very satisfied with the multi-dose delivery system. A significant majority (all p ≤ 0.045) of patients with a QuickDash® score between [0 to 25[ (66.4%, n = 211) and [50 to 75[ (81.8%, n = 11) rated multi-dose delivery system as easy or very easy to open and significantly more subjects in the [0 to 25[ (72%) score group rated multi-dose delivery system as being better or much better than their previous device (n = 211). Significantly (all p Conclusion The tested multi-dose delivery system was highly accepted. It is, therefore, suitable for glaucoma patients with decreased visual acuity and/or dexterity problems. Further studies may be necessary to assess the easiness of use of this easy-to-grip delivery system.

Electronic health (medical) records, which are also considered as patients’ information that are routinely collected, provide a great chance for researchers to develop an epidemiological understanding of disease. Electronic health records systems cannot develop without the advance of computer industries. While conducting clinical trials that are always costly, feasible and reasonable analysis of routine patients’ information is more cost-effective and reflective of clinical practice, which is also called real world study. Real world studies can be well supported by big data in healthcare industry. Real world studies become more and more focused and important with the development of evidence-based medicine. These big data will definitely help in making decisions, making policies and guidelines, monitoring of effectiveness and safety on new drugs or technologies. Extracting, cleaning, and analyzing such big data will be a great challenge for clinical researchers. Successful applications and developments of electronic health record in western countries (eg, disease registries, health insurance claims, etc) have provided a clear direction for Chinese researchers. However, it is still at primary stages in China. This review tries to provide a full perspective on how to translate the electronic health records into scientific achievements, for example, among patients with diabetes. As a summary in the end, resource sharing and collaborations are highly recommended among hospitals and healthcare groups.

Background and Aim Lenvatinib has been recently approved as a first‐line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real‐world setting. Methods Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria., Lenvatinib has been recently approved for patients with advanced hepatocellular carcinoma based on the results of the REFLECT trial, which excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We showed the efficacy and safety of lenvatinib for those patients and also for patients who did not meet the REFLECT inclusion criteria in a real‐world setting.

Aims In the PARADIGM‐heart failure trial, sacubitril‐valsartan demonstrated a reduction in heart failure admissions and reduced all‐cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. Methods and results This is a retrospective single‐centre review of patients switched from angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers to sacubitril‐valsartan between May 2016 and August 2018. Baseline and follow‐up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril‐valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril‐valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril‐valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. Conclusions Sacubitril‐valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril‐valsartan.

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday “real-world” practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed. The Salford Lung Study (SLS) was a world-first, prospective, phase III, pragmatic randomised controlled trial (RCT) programme in patients with chronic obstructive pulmonary disease and asthma to evaluate the effectiveness of a pre-licensed medication (fluticasone furoate/vilanterol) in real-world practice using electronic health records and through collaboratively engaging general practitioners and community pharmacists in clinical research. The real-world aspect of SLS was unique, requiring careful planning and attention to the goals of maximising the external validity of the trials while maintaining scientific rigour and securing suitable electronic processes for proper interpretation of safety data. Key learnings from SLS that may inform the design of future pragmatic effectiveness RCTs include: (1) ensuring the trial setting and operational infrastructure are aligned with routine clinical care; (2) recruiting a broad patient population with characteristics as close as possible to patients in routine clinical practice, to maximise the generalisability and applicability of trial results; (3) ensuring that patients and HCPs are suitably engaged in the trial, to maximise the chances of successful trial delivery; and (4) careful study design, incorporating outcomes of value to patients, HCPs, policymakers and payers, and using pre-planned analyses to address scientifically valid research hypotheses to ensure robustness of the trial data. Electronic supplementary material The online version of this article (10.1007/s12325-019-01192-1) contains supplementary material, which is available to authorized users.

Background and aim The hepatitis C virus (HCV) is considered a global health challenge that requires urgent interventions for prevention and control. In this study, we aimed to evaluate the effectiveness of direct-acting antiviral agents (DAAs) for HCV-infected patients in the Kingdom of Saudi Arabia (KSA). Patients and methods In this retrospective cohort study, we ascertained data of patients treated with DAA-based regimens for chronic HCV in the private health-care sector hospitals of KSA between April 2015 and December 2017. Data regarding presence or absence of liver cirrhosis, virus genotype, quantitative HCV RNA test, fibrosis stage, and history of liver disease were included. The primary end point of the study was the overall cure rate, defined as the number of patients achieving sustained viral response (SVR) rate at least 12 weeks following completion of treatment, divided by the total number of patients included in the study. Results A total of 262 patients fulfilled the study inclusion criteria. Adult patients were enrolled, of which 114 (44%) were females and 148 (56%) were males. About 105 of the patients (40%) were cirrhotic and 156 were treatment-naive patients (60%), 84 patients were interferon (INF) experienced, and 22 patients had previously received new DAAs but failed to achieve SVR. The majority of patients received ledipasvir-sofosbuvir±RBV (57%) with SVR rate of approximately 97%. Conclusions Our local real-world data indicate an overall HCV cure rate of 97% following treatment with DDA#x2019;s when prescribed in the private sector. This estimate is acquiescence with previously reported global cure rates.

Introduction The main objective of this study was to examine discontinuation rates associated with delayed-release dimethyl fumarate (DMF) when used for the treatment of relapsing multiple sclerosis (MS) in a real-world, clinical practice setting. Methods Data were collected retrospectively from charts of adult patients with relapsing–remitting MS treated at a single large institution in Australia, who completed at least 6 months of continuous therapy, either with DMF or another MS medication administered following DMF discontinuation. The primary endpoint was overall discontinuation rate. Secondary endpoints included discontinuation rate 6 months after initiation of DMF therapy; incidence of adverse events, particularly gastrointestinal events; discontinuation rate because of adverse events; and use of concomitant medications by patients during administration of DMF. Results A total of 100 patients initially prescribed DMF between October 1, 2013 and June 30, 2014 were included in the analysis. The mean age of the patients was 43 years and 80% were female. The overall discontinuation rate was 13%, with 9% discontinuing because of gastrointestinal tolerability issues, within the first 6 months. Dose changes as a result of adverse events occurred in 15% of patients, and none of the adverse events reported were serious. Only one patient discontinued owing to lack of efficacy. Conclusion This study, conducted shortly after the approval of DMF in Australia when first-hand clinical experience was still limited, demonstrated that DMF has an acceptable tolerability profile in the real-world setting that is similar to that demonstrated in clinical trials.

ObjectiveTo predict the real-world (RW) cost-effectiveness of carfilzomib in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in relapsed multiple myeloma (MM) patients after one to three prior therapies.MethodsA partitioned survival model that included three health states (progression-free, progressed disease and death) was built. Progression-free survival (PFS), overall survival (OS) and time to discontinuation (TTD) data for the Rd arm were derived using the Registry of Monoclonal Gammopathies in the Czech Republic; the relative treatment effects of KRd versus Rd were estimated from the phase 3, randomised, ASPIRE trial, and were used to predict PFS, OS and TTD for KRd. The model was developed from the payer perspective and included drug costs, administration costs, monitoring costs, palliative care costs and adverse-event related costs collected from Czech sources.ResultsThe base case incremental cost effectiveness ratio for KRd compared with Rd was €73,156 per quality-adjusted life year (QALY) gained. Patients on KRd incurred costs of €117,534 over their lifetime compared with €53,165 for patients on Rd. The QALYs gained were 2.63 and 1.75 for patients on KRd and Rd, respectively.ConclusionsCombining the strengths of randomised controlled trials and observational databases in cost-effectiveness models can generate policy-relevant results to allow well-informed decision-making. The current model showed that KRd is likely to be cost-effective versus Rd in the RW and, therefore, the reimbursement of KRd represents an efficient allocation of resources within the healthcare system.

Objective: The occurrence, development, and prognosis of serious adverse events (SAEs) associated with anticancer drugs in clinical trials have important guiding significance for real-world clinical applications. However, to date, there have been no studies investigating SAEs reporting in randomized clinical trials of colorectal cancer treatments. This article systematically reviewed the SAEs reporting of phase III randomized clinical trials of colorectal cancer treatments and analyzed the influencing factors.Methods: We reviewed all articles about phase III randomized clinical trials of colorectal cancer treatments published in the PubMed, Embase, Medline, and New England Journal of Medicine databases from January 1, 1993, to December 31, 2018, and searched the registration information of clinical trials via the internet sites such as “clinicaltrials.gov”. We analyzed the correlation between the reported proportion (RP) of SAEs in the literature and nine elements, including the clinical trial sponsor and the publication time. Chi-square tests and binary logistic regression were used to identify the factors associated with improved SAEs reports. This study was registered on PROSPERO.Results: Of 1560 articles identified, 160 were eligible, with an RP of SAEs of 25.5% (41/160). In forty-one publications reporting SAEs, only 14.6% (6/41) described the pattern of SAEs in detail. In clinical trials sponsored by pharmaceutical companies, the RP of SAEs was significantly higher than that in those sponsored by investigators (57.6 versus 20.7%, p < 0.001). From 1993 to 2018, the RP of SAEs gradually increased (none (0/6) before 2000, 17.1% (12/70) from 2000 to 2009, and 34.5% (29/84) after 2009). The average RP of SAEs published in the New England Journal of Medicine (N Engl J Med), the Lancet, the Journal of the American Medical Association (JAMA), the Lancet Oncology (Lancet Oncol), and the Journal of Clinical Oncology (J Clin Oncol) was significantly higher than that published in other journals (31.9 versus 16.7%, p = 0.030). In the clinical trials referenced by clinical guidelines, the RP of SAEs was higher than that in non-referenced clinical trials (32.0 versus 15.9%, p = 0.023). Binary logistic regression analysis showed that pharmaceutical company sponsorship, new drug research, and sample size greater than 1000 were positive influencing factors for SAEs reporting.Conclusion: Although the RP of SAEs increased over time, SAEs reporting in clinical trials needs to be further improved. The performance, outcomes and prognosis of SAEs should be reported in detail to guide clinical practice in the real world.

The current COVID pandemic crisis made it even clearer that the solutions to several questions that public health must face require the access to good quality data. Several issues of the value and potential of health data and the current critical issues that hinder access are discussed in this paper. In particular, the paper (i) focuses on “real-world data” definition; (ii) proposes a review of the real-world data availability in our country; (iii) discusses its potential, with particular focus on the possibility of improving knowledge on the quality of care provided by the health system; (iv) emphasizes that the availability of data alone is not sufficient to increase our knowledge, underlining the need that innovative analysis methods (e.g., artificial intelligence techniques) must be framed in the paradigm of clinical research; and (v) addresses some ethical issues related to their use. The proposal is to realize an alliance between organizations interested in promoting research aimed at collecting scientifically solid evidence to support the clinical governance of public health.

Background Although canakinumab has demonstrated efficacy in multiple trials in patients with periodic fever syndromes (PFS), the evidence on initiation of canakinumab among PFS patients in real world setting is not well understood. We aimed to characterize the reasons for canakinumab initiation among patients with PFS, specifically, cryopyrin-associated periodic syndrome (CAPS), hyperimmunoglobulin D syndrome/mevalonate kinase deficiency (HIDS/MKD), TNF receptor-associated periodic syndrome (TRAPS) and familial Mediterranean fever (FMF). Methods Physicians retrospectively reviewed the medical charts of PFS patients prescribed canakinumab between 2016 and 2018. Information collected included patient clinical characteristics, reasons for previous treatment discontinuation and canakinumab initiation. The results were summarized for overall patients, and by children ( Results Fifty-eight physicians in the US (rheumatologists, 44.8 %; allergists/immunologists, 29.3 %; dermatologists, 25.9 %) abstracted information for 147 patients (children, 46.3 %; males, 57.1 %; CAPS, 36.7 %; TRAPS, 26.5 %; FMF, 26.5 %; HIDS/MKD, 6.8 %; Mixed, 3.4 %). Overall, most patients (90.5 %) received treatment directly preceding canakinumab (NSAIDs, 27.8 % [40.0 % in HIDS/MKD]; anakinra, 24.1 % [32.7 % in CAPS]; colchicine, 21.8 % [35.9 % in FMF]), which were discontinued due to lack of efficacy/effectiveness (39.5 %) and availability of a new treatment (36.1 %). The common reasons for canakinumab initiation were physician perceived efficacy/effectiveness (81.0 %; children, 75.0 %; adults, 86.1 %), lack of response to previous treatment (40.8 %; children, 38.2 %; adults, 43.0 %) and favorable safety profile/tolerability (40.1 %; children, 42.6 %; adults, 38.0 %). Within subtypes, efficacy/effectiveness was the most stated reason for canakinumab initiation in HIDS/MKD (90.9 %), lack of response to previous treatment in FMF (52.4 %) and convenience of administration/dosing in CAPS (27.1 %). Conclusions This study provided insights into how canakinumab is initiated in US clinical practice among PFS patients, with physician perceived efficacy/effectiveness of canakinumab, lack of response to previous treatment and favorable safety profile/tolerability of canakinumab being the dominant reasons for canakinumab initiation in all patients and in children and adults and PFS subtypes. Notably, the favorable safety profile/tolerability of canakinumab was more often the reason for initiation among children versus adults.

Introduction: Real-world data indicate disparities in biologic access across Europe. Objectives: To describe the national structure of PsA care in Poland, with a particular focus on the population of inadequate responders (IRs) and difficulties associated with biologic therapy access. Methods: A pool of rheumatologic and dermatologic care centers was created based on National Health Fund contract lists (n = 841), from which 29 rheumatologic and 10 dermatologic centers were sampled randomly and successfully met the inclusion criterium. Additionally, 33 tertiary care centers were recruited. For successful center recruitment, one provider had to recruit at least one patient that met the criteria for one of the four pre-defined clinical subgroups, in which all patients had to have active PsA and IR status to at least 2 conventional synthetic disease-modifying drugs (csDMARDs). Self-assessment questionnaires were distributed among physicians and their patients. Results: Barriers to biologic DMARD (bDMARD) treatment are complex and include stringency of reimbursement criteria, health care system, logistic/organizational, and personal choice factors. For patients who are currently bDMARD users, the median waiting time from the visit, at which the reimbursement procedure was initiated, to the first day of bDMARD admission was 9 weeks (range 2–212, 32% &lt, 4 weeks, 29% 5–12 weeks, 26% 13–28 weeks, 13% with &gt, 28 weeks delay). Out of all inadequate responder groups, bDMARD users are the only group with “good” therapeutic situation and satisfaction with therapy. Patient satisfaction with therapy is not always concordant with physician assessment of therapeutic status. Conclusions: Despite the fact that over a decade has passed since the introduction of biologic agents, in medium welfare countries such as Poland, considerable healthcare system barriers to biologic access are present. Out of different IR populations, patient satisfaction with treatment is often discordant with physician assessment of disease status.

IL-23-inhibitors, such as guselkumab and risankizumab, represent the newest class of biologics approved for psoriasis. Phase III trials have shown their efficacy and safety. However, real life data are still scant. to indirectly compare the effectiveness, safety and tolerability of guselkumab and risankizumab in real world practice. An Italian single-center retrospective cohort study enrolling moderate-to-severe psoriasis patients from September 1, 2018 and December 31, 2020 was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Sixty eight patients were included (36 received guselkumab and 32 risankizumab). The groups were comparable for all analyzed characteristics, except for mean psoriasis duration (p

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

Background: There are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR) mutations. Methods: Patients with advanced NSCLC ( N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed. Results: The gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57–0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65–1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p Conclusion: Compared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR-mutated NSCLC.

BackgroundAfatinib is approved for first-line treatment of patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Here, we report findings from a combined analysis of three phase IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naïve patients.MethodsEGFR-TKI-naïve patients withEGFRm+ NSCLC received afatinib 40 mg/day. Dose reductions were permitted for adverse events (AEs). Efficacy endpoints included progression-free survival (PFS), time to symptomatic progression (TTSP), and tumor response. Subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, age and common/uncommonEGFRmutations (plus other factors).Results1108 patients were treated. Median age was 61 years (range, 25–89); 19.2% had baseline brain metastases, 4.4% had ECOG PS ≥2, and 17.9% had tumors harboring uncommon mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 months [95% confidence interval (CI): 12.0–13.8]; median TTSP was 14.8 months (95% CI: 13.9–16.1). Objective response rate (ORR) was 55.0%. Age, presence of baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer in patients with ECOG PS 2 or exon 20 insertion/T790M mutations.ConclusionsAfatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommonEGFRmutations.

We aimed to compare real-world outcomes, resource use, and costs for patients with newly diagnosed multiple myeloma (NDMM) treated with continuous first-line (1 L) lenalidomide or fixed bortezomib in Europe. We performed a multicenter, retrospective, observational chart review of transplant-ineligible NDMM patients across 7 countries. Of 453 eligible patients, 220 received 1 L lenalidomide-based regimens; 105 (47.7%) received second-line (2 L) treatment, of which 50 (47.6%) received 2 L bortezomib. 233 patients received 1 L bortezomib-based regimens; 142 (60.9%) had 2 L treatment, of which 104 (73.2%) received 2 L lenalidomide. Patients receiving 1 L lenalidomide-based regimens had better progression-free survival than patients receiving 1 L bortezomib-based regimens (p =.002) and a longer time to 2 L or third-line treatment (both p

There are limited real-world data on the treatment practices and healthcare resource utilization associated with chronic lymphocytic leukemia (CLL) in Japan. In this study (CLIMBER-DBR), we performed retrospective analyses of the Japanese Medical Data Vision database, and extracted data for 2562 patients with newly diagnosed CLL (CLL-1 cohort) and 930 patients receiving CLL treatment (CLL-2 cohort) registered between March 1, 2013 and February 28, 2018. The median follow-up in the CLL-1 cohort was 721 (quartile 1-3: 363-1267) days and the median time to initial (first-line) treatment was 1331 (quartile 1-3: 189-not reached) days. In the CLL-2 cohort, the most frequently used regimens were fludarabine alone (17.7%), cyclophosphamide alone (13.7%), and bendamustine/rituximab (8.2%). The median (quartile 1-3) times to second-line and third-line treatments were 1066 (273-not reached) and 1795 (631-not reached) days, respectively. The CLIMBER-DBR was the first database research study to assess current treatment practices for CLL in Japan, where the treatment patterns were driven by the approval/reimbursement status of drugs in the study period. Our study provides an important benchmark for future studies of CLL in Japan.

Background The nature of COVID-19 pandemic measures has altered the clinical management of migraine, and has also created barriers to evaluate the impact of such measures of migraine patients. Using the Migraine Buddy smartphone application, we assessed the impact of the COVID-19 pandemic on migraine in users residing in the United States. Methods Migraine Buddy is a smartphone application by individuals to record their migraine headache episodes, characteristics, and coping mechanisms. For this study, anonymized self-reported data from 163,176 adult Migraine Buddy users in the United States between January 2020 and May 2020, were analyzed for migraines associated with stress. A stress-related migraine is defined as one in which stress or anxiety was reported as a trigger or symptom. A questionnaire on the impact of COVID-19 on migraine and its management was also completed by 923 users from the United States in the app between April 2020 and May 2020. Results 88% of the Migraine Buddy database extract and 84% of the respondents are female, with a mean age of 36.2 years. The proportion of stress-related migraine attacks peaked at 53% on March 21 to 23, although the number of migraine attacks decreased. This followed the declaration of the COVID-19 national emergency on March 13 and a spike in the number of COVID-19 cases in the United States. Questionnaire respondents felt that the following added more stress: social isolation (22.6%), information overdose (21.2%), access to essentials (food, medication, etc.) (18.7%), and financial concerns (17.8%). To help manage migraine during COVID-19, respondents suggested stress and diet coaching programs and resources (medical articles, etc.) (34.0%), having the option for home delivery of medication (30.6%) and tele-consulting (25.5%). Conclusion Here, we report the change in the proportion of self-reported stress-related migraine in relation to evolution of the COVID-19 pandemic, as well as its impact of migraine management. Our data will help increase the understanding of patients’ needs and help with planning and execution of mitigating strategies.