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Background and Aims This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn’s disease [CD] patients. Methods This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. Results A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28–0.62]) and SIs (HR = 0.40 [0.19–0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45–0.76]). Other outcomes did not significantly differ between groups. Conclusion In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.

Objective Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Methods Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan–Meier curves, log-rank test and multivariable Cox’s models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Results Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium’s good prognosis (P Conclusions In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium’s favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium’s good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

Introduction The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE. Methods OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults ≥ 18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score ≥ 10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated. Results In total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a ≥ 50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to ≥ 80% improvement). Initiating belimumab while on high-dose (> 7.5 mg/day) GCS use was associated with ≥ 50% clinical improvement at month 6 (OR: 1.9, p = 0.003). Most (78.1%; n = 518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of − 8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was − 5.7 (4.5; n = 344). Conclusions Belimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE. Electronic Supplementary Material The online version of this article (10.1007/s40744-020-00243-2) contains supplementary material, which is available to authorized users.

Fulvestrant 500 mg is standard of care for endocrine therapy‐naive or pretreated women with hormone receptor‐positive (HR+) metastatic breast cancer (MBC). This study was conducted to explore the potential factors and duration of last endocrine therapy as predictors for the efficacy of fulvestrant 500 mg on Chinese patients in real‐world practice. Two hundred and fifty‐two MBC patients who were treated with fulvestrant 500 mg consecutively between January 2011 and December 2015 in our institute were included in this study. Efficacy outcomes included progression‐free survival (PFS), overall survival (OS), and clinical benefit rate (CBR). The optimal cut‐off value for duration of last endocrine therapy was determined by survival ROC analysis. Adverse events were graded according to NCI‐CTC AE 4.0. Fulvestrant 500 mg demonstrated a median PFS of 5.8 months (95%CI 4.6‐6.9), and a median OS of 35.9 months (95%CI 30.2‐41.4). CBR was 41.3% (95%CI 35‐47). Liver metastasis, bone alone metastasis, lines of endocrine therapy for MBC, and sensitivity to last endocrine therapy were statistically significant in the Cox multivariate analysis (P values of 0.022, 0.02, 0.03, and 0.038, respectively). The optimal cut‐off values for duration of last endocrine therapy to predict the efficacy of fulvestrant 500 mg were 25.08 months for adjuvant endocrine therapy and 5.17 months for first‐line endocrine therapy, which showed no difference in prediction power with ABC clinical definition. Patients with prior adjuvant endocrine therapy ≥25.08 months or first‐line therapy≥5.17 months reached a longer PFS of fulvestrant (p = 0.04). Six patients discontinued the treatment due to intolerable adverse events. Patients with the duration of prior endocrine therapy longer than optimal cut‐off points indicate better PFS of fulvestrant. Liver metastasis, bone alone metastasis, line of fulvestrant, and sensitivity to last endocrine therapy were also predictors for response of fulvestrant. ClinicalTrials.gov Identifier: NCT03708432., This study provided first‐hand data regarding the efficacy and safety profile of fulvestrant 500 mg in Chinese patients with HR+/HER2‐ MBC. We successively collected all patients treated with fulvestrant within a certain period of time to delineate the pattern of real‐world practice. The study identified potential determinants that were significantly associated with PFS of fulvestrant 500 mg.

AASLD - TASL Connect Regional Meeting -- MAR 15-16, 2019 -- Istanbul, TURKEY WOS:000535263200004 PubMed: 32412901 Background/Aims: mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) +/- dasabuvir (DSV) +/- ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r +/- DSV +/- RBV combination regimen in a real-world clinical practice. Materials and Methods: Data from HCV genotype 1 and 4 patients treated with OMV/PTV/r +/- DSV +/- RBV (n=862) in 34 centers across Turkey between April 1, 2017 and August 31, 2018 were recorded in a large national database. Demographic, clinical, and virologic data were analyzed. Results: The mean age of the patients was 55.63, and 430 patients (49.9%) were male. The majority had HCV genotype 1b infection (77.3%), and 66.2% were treatment-naive. Non-cirrhosis was present at baseline in 789 patients (91.5%). SVR12 rate was 99.1% in all patients. Seven patients had virologic failure. No significant differences were observed in SVR12 according to HCV genotypes. HCV RNA was undetectable at treatment week 4 in 90.9%, at treatment week 8 in 98.5%, and at the end of treatment (EOT) in 98.9%. SVR12 ratio was significantly higher in the non-cirrhotic patients compared to that in the compensated cirrhotic patients. Rates of adverse events (AEs) in the patients was 59.7%. Conclusion: The present real-life data of Turkey for the OBV/PTV/r +/- DSV +/- RBV treatment of patients with HCV genotype 1b, 1a, or 4 infection from 862 patients demonstrated high efficacy and a safety profile. AASLD, TASL

IntroductionAnti-tumour necrosis factor (TNF) therapy has greatly improved treatment outcomes in patients with inflammatory bowel disease (IBD), but long-term use is associated with cutaneous reactions, susceptibility to infections and frequent injections or hospital visits. Several non-controlled studies have demonstrated that dose reduction is feasible for a subset of patients, provided that early detection of a disease flare is possible. Here, we aim to compare the effectiveness of interval lengthening with standard dosing in maintaining remission in young patients with IBD.Methods and analysisIn this international, prospective, non-inferiority, partially randomised patient preference trial, we aim to recruit 148 patients aged 12–25 years with luminal Crohn’s disease or ulcerative colitis in sustained remission (ie, three consecutive in-range faecal calprotectin (FC) results or recently confirmed endoscopic remission). In the interventional arm, the dosing interval will be lengthened from 8 to 12 weeks for infliximab users and from 2 to 3 weeks for adalimumab users. In the control group, standard dosing will be continued. Rapid tests will be performed for FC every 4 weeks and for anti-TNF trough levels every 12 weeks. The primary outcome is the cumulative incidence of out-of-range FC results at 48-week follow-up. Secondary endpoints include time to get out-of-range FC results, cumulative incidence of adverse effects, proportion of patients progressing to loss of response and identification of predictors of successful interval lengthening.Ethics and disseminationThe protocol has been approved by the Medical Ethics Review Committee of the University Medical Centre Groningen and is pending at the other participating centres. Results will be disseminated in peer-reviewed journals and presented at scientific meetings.Trial registration numberEudraCT number: 2020-001811-26; ClinicalTrials.gov Identifier: NCT04646187. Protocol version 4, date 17 September 2021.

Background: There is limited data on the relative survival rate of first-line therapy of gefitinib, erlotinib (first-generation epidermal growth factor receptor-tyrosine kinase inhibitor [EGFR-TKI]), and afatinib (second-generation EGFR-TKI) in patients with EGFR-mutated advanced lung adenocarcinoma in real-world data, especially in the Asian population. This study aimed to compare the relative survival rate of gefitinib, erlotinib, and afatinib in patients with EGFR-mutated advanced lung adenocarcinoma by real-world data in Taiwan.Methods: This retrospective cohort population-based study included untreated adult patients diagnosed with advanced lung adenocarcinoma who were identified in the Taiwan National Health Insurance Research Database between 2014 and 2017. The date of EGFR-mutated advanced lung adenocarcinoma diagnosis was referred as index date. This outcome evaluated overall survival (OS) and time to treatment failure (TTF) between gefitinib, erlotinib, and afatinib. Switching EGFR-TKIs or chemotherapy and new development of brain metastases were proxies of TTF. Estimated relative treatment effects on OS and TTF among EGFR-TKIs were adjusted by inverse probability of treatment weighting (IPTW) in Cox proportional hazards model. Propensity score (PS) matched pair analyses were performed as sensitivity analyses.Results: The study cohort included 3,695 patients initiated with gefitinib, 3,310 with erlotinib, and 3,041 with afatinib. The mean age among the three treatment groups was 70.4 (±11.6), 66.8 (±11.6), and 64.3 (±11.4) years, and the female percentage was 70.4, 58.6, and 57.7%, respectively. Afatinib showed longer median OS than gefitinib (23.9 vs. 21.3 months; adjusted hazard ratio (aHR), 0.87; p < 0.001) and erlotinib (23.9 vs. 21.8 months; aHR, 0.87; p = 0.001). Consistent results were observed with TTF outcomes. For patients with brain metastases at diagnosis, afatinib showed similar OS with erlotinib (p = 0.917) but superior to gefitinib (p = 0.028). PS matching had similar results with IPTW adjustment in the study population.Conclusion: Afatinib as first-line therapy had better survival outcomes for EGFR-mutated advanced lung adenocarcinoma than gefitinib and erlotinib in the Taiwan population. Both erlotinib and afatinib demonstrated superior treatment effect in patients with initial brain metastases than gefitinib.

Introduction Treatment of neovascular age-related macular degeneration (nAMD) has evolved with the advent of anti-vascular endothelial growth factor agents such that intravitreally administered aflibercept and ranibizumab (RBZ) have become the standard of care. Randomized clinical trials (RCTs) have demonstrated the benefits of these agents in nAMD; however, results achieved under RCT protocols may not always be replicated in clinical practice. Assessing real-world outcomes is important to estimate the effectiveness and cost-effectiveness of these two agents. Our objective was to assess the real-world effectiveness of intravitreally administered aflibercept and RBZ in treatment-naive patients with nAMD and determine the cost-effectiveness of intravitreally administered aflibercept versus RBZ in a real-world setting. Methods A multistage approach was undertaken. A systematic literature review (SLR) was completed to identify studies describing real-world outcomes in patients with nAMD treated intravitreally with aflibercept or RBZ. A meta-analysis of data identified in the SLR generated a pooled estimate of the effectiveness of intravitreally administered aflibercept and RBZ at 52 weeks and an estimate of treatment burden (injection frequency and monitoring). The impact of treatment effect modifiers, such as baseline visual acuity (VA) and age, were corrected through a multivariable meta-regression. A Markov state transition model was developed to estimate the real-world cost-effectiveness of intravitreally administered aflibercept using results from the pooled estimates for effectiveness and treatment burden as primary inputs. The analysis considered the perspective of the French National Healthcare System. Results Patients treated intravitreally with aflibercept had a mean age of 79.52 years and mean baseline VA of 55.80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. At week 52, mean VA gain was 5.30 ETDRS letters in patients reporting an average of 7.10 intravitreal injections of aflibercept and 8.65 visits (injection and/or monitoring). RBZ-treated patients were younger (77.28 years), with a lower mean baseline VA (52.81 ETDRS letters). At week 52, mean VA gain from baseline was 4.24 ETDRS letters, with an average of 5.88 injections and 10.10 visits (injection and/or monitoring). After correcting for differences in age (77.28 years) and baseline VA (52.81 ETDRS letters) and considering the current clinical practice with aflibercept and RBZ, the mean VA gain was 6.57 ETDRS letters for patients treated intravitreally with aflibercept and 4.42 ETDRS for patients treated intravitreally with RBZ. The cost-effectiveness analysis showed that intravitreally administered aflibercept is a more effective treatment option with an incremental gain in quality-adjusted life years (QALYs) (4.918 versus 4.880) and an incremental cost-effectiveness ratio (ICER) of €27,087 per QALY. Conclusions The analysis identified differences in the overall treatment approach and how ophthalmologists use intravitreally administered aflibercept and RBZ in clinical practice. These differences ultimately influence the mean real-world effectiveness of the two agents. Intravitreal treatment with aflibercept (injection frequency and patients follow-up) was consistent and in line with the European label recommendations. Patients treated intravitreally with aflibercept in clinical practice reported a mean gain in VA of similar magnitude to the mean VA gain reported in the pivotal RCT. Conversely, treatment with RBZ varied significantly across the different studies. On average, RBZ-treated patients reported a low injection frequency and a frequent follow-up, driven in part by the high number of patients treated with pro re nata (PRN) regimens. RBZ-treated patients reported gains in VA versus baseline; however, the magnitude of the gain in VA was not comparable to the VA gains reported in the RBZ pivotal RCT. Intravitreal treatment with aflibercept was associated with better mean VA outcomes and an incremental gain in QALYs compared with RBZ and can be considered cost-effective for the treatment of nAMD in patients in France despite a higher price for each individual intravitreal injection of aflibercept compared with RBZ. Funding Bayer AG, Basel. Electronic supplementary material The online version of this article (10.1007/s12325-019-01147-6) contains supplementary material, which is available to authorized users.

In this real-world analysis, patients with ulcerative colitis frequently required steroids up to a year after initiating immunosuppressant or biologic therapies, with high ulcerative colitis-related costs. This suggests an ongoing challenge in managing patients with moderate to severe ulcerative colitis., Background Ulcerative colitis (UC) treatment aims to induce response and maintain steroid-free remission. For patients with moderate to severe UC and/or nonresponse to conventional treatment, advanced therapies (immunosuppressants and biologics) are available. We assessed real-world effectiveness of advanced UC therapies. Methods This retrospective analysis of claims data included adult patients with UC initiating immunosuppressant or biologic therapy, with 12 months’ continuous enrollment pre- and postinitiation. Patients had no prescription for biologic therapy (and/or immunosuppressant if initiating immunosuppressant) in the previous 12 months. Proportion of patients remaining steroid-free (excluding 14-week tapering period), hospitalizations, and costs in the 12 months postinitiation were assessed. Results In total, 3562 patients were included in the analysis. Most patients (83.0%) used steroids in the 12 months before initiating advanced therapy. Overall, 47.8% remained steroid-free after 12 months (excluding tapering). After adjusting for patient characteristics, remaining steroid-free was significantly more likely with infliximab (43.9%) than with adalimumab (39.4%; P < 0.05); golimumab (38.2%) and vedolizumab (41.4%) were not significantly different vs adalimumab. Overall, 12.2% of patients had a UC-related hospitalization within 12 months of initiation, with a mean (SD) total length of stay of 8.2 (8.9) days and no significant differences between biologic therapies. Mean, unadjusted, UC-related costs in the 12 months postinitiation were $42,579 and were similar between therapies. Conclusions Patients with UC initiating advanced therapy frequently continued using steroids for at least a year. Some patients experienced extended UC-related hospitalizations, with high UC-related costs overall. This suggests an ongoing challenge in managing patients with moderate to severe UC.

BackgroundBoth Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).MethodsWe conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.ResultsAfter a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.ConclusionsIn this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.

BACKGROUND: The present retrospective, longitudinal cohort study assessed the association between the first-line sunitinib treatment duration and clinical outcomes with second-line immuno-oncology (IO) therapy among patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 161 patients with mRCC who had been treated with first-line sunitinib and subsequent IO therapy from select International mRCC Database Consortium centers were included. The overall survival, time to next therapy, time to treatment discontinuation, and real-world physician-assessed best response measured from IO therapy initiation were analyzed and compared between patients treated with first-line sunitinib for ≥ 6 months and those treated for < 6 months. RESULTS: The 116 patients treated with sunitinib for ≥ 6 months tended to be older and to have a better International mRCC Database Consortium risk than the 45 patients treated for < 6 months (favorable, 36% vs. 8%, P = .001; intermediate, 59% vs. 70%, P = .21; poor, 5% vs. 22%, P = .007). The receipt of sunitinib for ≥ 6 months versus < 6 months was associated with longer survival (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = .02). No significant association was observed between the first-line sunitinib duration and second-line IO outcomes, including the time to next therapy (HR, 0.89; 95% CI, 0.52-1.51; P = .66), time to treatment discontinuation (HR, 0.85; 95% CI, 0.54-1.34; P = .49), and tumor response (odds ratio, 0.73; 95% CI, 0.22-2.49; P = .62). CONCLUSIONS: We found no statistically significant association between the first-line sunitinib duration and clinical outcomes with second-line IO therapy. Patients receiving first-line sunitinib for ≥ 6 months compared with < 6 months was associated with better overall survival, although potential unadjusted confounders could have been present. These findings support the paradigm that previous therapy will not dictate the effectiveness of subsequent immunotherapy. ispartof: CLINICAL GENITOURINARY CANCER vol:18 issue:4 pages:E350-E359 ispartof: location:United States status: published

Background Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness. Methods A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn’s disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014–June 22, 2017. Response and remission rates were combined in random-effects meta-analyses. Results At treatment week 14, 32% of UC patients [95% confidence interval (CI) 27–39%] and 30% of CD patients (95% CI 25–34%) were in remission; and at month 12, 46% for UC (95% CI 37–56%) and 30% for CD (95% CI 20–42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20–34%) and 42% at month 12 (95% CI 31–53%); for CD they were 25% at week 14 (95%, CI 20–31%) and 31% at month 12 (95%, CI 20–45%). At month 12, 33–77% of UC and 6–63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events. Conclusions Vedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit–risk profile of vedolizumab. Electronic supplementary material The online version of this article (10.1007/s00535-018-1480-0) contains supplementary material, which is available to authorized users.

Riccardo Di Domenicantonio,1 Francesco Trotta,1 Silvia Cascini,1 Nera Agabiti,1 Anna Kohn,2 Antonio Gasbarrini,3 Marina Davoli,1 Antonio Addis1 1Department of Epidemiology, Lazio Regional Health Service, Rome, Italy; 2IBD Unit, AO San Camillo Forlanini, Rome, Italy; 3Department of Internal Medicine, Agostino Gemelli University Hospital, Catholic University of Sacred Heart, Rome, Italy Background: The comparison of effectiveness and safety of anti-tumor necrosis factor-alpha agents for the treatment of inflammatory bowel disease (IBD) is relevant for clinical practice and stakeholders. Objective: The objective of this study was to compare the risk of abdominal surgery, steroid utilization, and hospitalization for infection in Crohn’s disease (CD) or ulcerative colitis (UC) patients newly treated with infliximab (IFX) or adalimumab (ADA). Methods: A retrospective population-based cohort study was performed using health information systems data from Lazio region, Italy. Patients with CD or UC diagnosis were enrolled at first prescription of IFX or ADA during 2008–2014 (index date). Only new drug users were followed for 2 years from the index date. IFX versus ADA adjusted hazard ratios were calculated applying “intention-to-treat” approach, controlling for several characteristics and stratifying the analysis on steroid use according to previous drug utilization. Sensitivity analyses were performed according to “as-treated” approach, adjusting for propensity score, censoring at switching or discontinuation, and evaluating different lengths of follow-up periods. Results: We enrolled 1,432 IBD patients (42% and 83% exposed to IFX for CD and UC, respectively). In both diseases, treatment effects did not differ in any outcome considered, and sensitivity analyses confirmed the results from the main analysis. Conclusion: In our population-based cohort study, effectiveness and safety data in new users of ADA or IFX with CD or UC were comparable for the outcomes we tested. Keywords: biologics, real-world effectiveness, inflammatory bowel disease

Chad Moretz,1 Lucie Sharpsten,2 Lindsay GS Bengtson,2 Eleena Koep,2 Lisa Le,2 Junliang Tong,2 Richard H Stanford,1 Beth Hahn,1 Riju Ray31US Value Evidence and Outcomes, GSK, Durham, NC, USA; 2Health Economics and Outcomes Research, Optum, Eden Prairie, MN, USA; 3US Medical Affairs, GSK, Durham, NC, USABackground and objective: Retrospective claims data in patients with chronic obstructive pulmonary disease (COPD) initiating maintenance therapy with inhaled fixed-dose combinations of long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) versus inhaled corticosteroid (ICS)/LABA have not been reported.Methods: Retrospective observational study in a COPD-diagnosed population of commercial and Medicare Advantage with Part D (MAPD) enrollees aged ≥40 years from a US health insurer database. Patients initiated umeclidinium/vilanterol (UMEC/VI [62.5/25 μg]) or fluticasone propionate/salmeterol (FP/SAL [250/50 μg]) between April 1, 2014 and August 31, 2016 (index date) and had 12 months continuous enrollment pre- and post-index. Exclusion criteria included an asthma diagnosis in the pre-index period/index date; ICS-, LABA-, or LAMA-containing therapy during the pre-index period; or pharmacy fills for both UMEC/VI and FP/SAL, multiple-inhaler triple therapy, a non-index therapy, or COPD exacerbation on the index date. Adherence (proportion of days covered [PDC] ≥80%) was modeled using weighted logistic regression following inverse probability of treatment weighting (IPTW). Weighted Kaplan–Meier and Cox proportional hazards regression following IPTW were performed for incidence of COPD exacerbation and escalation to multiple-inhaler triple therapy.Results: The study population included 5306 patients (1386 initiating UMEC/VI and 3920 initiating FP/SAL). Adjusted odds of adherence were 2.00 times greater among UMEC/VI than FP/SAL initiators (95% confidence interval [CI]: 1.62─2.46; P

Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Patients and Methods: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusion: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

The direct-acting antiviral regimen of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) demonstrated high rates of sustained viral response at post-treatment week 12 (SVR12) in clinical trials for treatment of hepatitis C virus (HCV) genotypes (GT) 1 and 4. To confirm the effectiveness of this regimen in the real world, we conducted meta-analyses of published literature on 30 April 2016. Freeman-Tukey transformation determined the SVR rate within GTs 1a, 1b, and 4, as well as specific SVR rates by cirrhosis or prior treatment experience status. Rates of virologic relapse, hepatic decompensation, drug discontinuation, and serious adverse events were also analyzed. In total, 20 cohorts across 12 countries were identified, totaling 5,158 patients. The overall SVR12 rates were 96·8% (95% CI 95·8 – 97·7) for GT1 and 98·9% (95% CI 94·2 – 100) for GT4. For GT1a patients, the SVR rates were 94% and 97% for those with or without cirrhosis, and 94% overall. For GT1b patients, the SVR rates were 98% and 99% for those with or without cirrhosis, and 98% overall. The virologic relapse rate of GT1 patients was 1·3%, across 3524 patients in 9 studies that reported this parameter. The rate of hepatic decompensation was less than 1% across 5 studies, including 3440 patients, 70% of which had cirrhosis. Conclusions Real world SVR12 rates for OBV/PTV/r ± DSV ± RBV were consistently high across HCV GT1 and 4 irrespective of cirrhosis status or prior HCV treatment experience, confirming effectiveness within a diverse patient population across multiple cohorts and countries. This article is protected by copyright. All rights reserved.

ObjectiveTo compare the effectiveness and cost-effectiveness among generic and branded statins in routine clinical practice.MethodsRetrospective database study of patients, 18+, who were newly prescribed statin therapy. Statin effectiveness and cost-effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and attaining LDL-C goals were evaluated.ResultsOf 10,421 eligible patients, % LDL-C reduction was significantly greater (P < 0.001) with rosuvastatin (−31.6%) than other statins (−13.9 to −21.9%). Percentage of patients at moderate/high risk attaining LDL-C goal was higher (P < 0.001) for rosuvastatin (76.1%) versus other statins (57.6–72.6%). Rosuvastatin was more effective and less costly than atorvastatin. Among generic statins, simvastatin required >61% discount to branded price to achieve similar cost-effectiveness as generic lovastatin.ConclusionsIn clinical practice, rosuvastatin is more effective and less costly in lowering LDL-C and LDL-C goal attainment compared with atorvastatin. Simvastatin was more cost-effective compared with lovastatin if >61% discount to branded price was achieved.

Objective To examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting. Methods This observational cohort study was conducted in US clinical practices. Rheumatologists (n=92) identified adults with SLE who had received ≥8 infusions of belimumab plus standard of care (SoC). Physicians assessed disease outcomes at 6-month intervals using patient medical charts, for up to 24 months. The primary outcome was physician-assessed change in SLE disease. Other outcomes included change in steroid use, laboratory tests and healthcare resource utilisation (HCRU). Results Of 501 patients (intent-to-treat population (ITT)), 446 were female, mean age was 43.3 years and 98% had moderate/severe disease activity at baseline (first dose of belimumab). Data for 277 patients who completed 24 months of belimumab treatment were available. Among the ITT, a ≥50% improvement in overall clinical response between baseline and month 6 was reported for 48.7% of patients; continued improvement was seen at all subsequent 6-month intervals relative to the previous timepoint. The percentage of patients with moderate/severe disease also decreased at each timepoint. At baseline, 77.0% of patients received steroids at a mean (SD) prednisone equivalent dose of 19.9 (14.39) mg/day, which decreased to 8.4 (7.35) mg/day at month 6 and 6.1 (9.31) mg/day at month 24. Abnormal laboratory values typically associated with SLE also demonstrated improvements at month 6, which continued through 24 months. HCRU decreased over the duration of the study. Conclusions Patients with SLE who received belimumab plus SoC for up to 24 months demonstrated improvements in disease severity and laboratory values and a reduction in steroid use and HCRU as early as month 6. Improvements continued through 24 months, providing evidence of reduced disease activity among patients taking belimumab in real-world clinical practice.

Summary This study demonstrates real-world effectiveness of teriparatide in reducing the risk of hip and other fragility fractures. Fracture incidence significantly decreased as adherence and persistence increased for any clinical, vertebral, nonvertebral, and hip fractures among patients who were observed for 2 years after teriparatide initiation. Introduction Examine the relationship of treatment adherence and persistence to teriparatide with hip and other fractures. Methods Truven MarketScan Research Databases, 2004 through 2014, provided teriparatide users ≥18 years old with continuous coverage 12 months pre- and 24 months post-teriparatide prescription. Adherence (medication possession ratio, MPR) groups were defined as high (≥0.80), medium (0.50 ≤ MPR