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Introduction Real-world treatment persistence to ustekinumab for Crohn’s disease (CD) was studied using Australian Pharmaceutical Benefits Scheme (PBS) data. Demographic and treatment pattern characteristics were also investigated. Methods Our retrospective cohort analysis included PBS 10% sample data for ustekinumab from September 2017 to March 2020, and for other biologics from October 2007 to capture earlier line(s) of therapy. Included patients received ustekinumab for CD prescribed by a gastroenterologist. Treatment persistence overall and by prior biologic experience, mono- or combination therapy, sex and age were estimated using Kaplan–Meier methods. A Cox proportional hazards regression analysis was performed to assess the effect of age, sex and line of therapy on persistence. Results Data were available for 301 patients. Of these, 58.8% were female and 76.7% were aged 26–65 years. Median follow-up from first ustekinumab dispense was 16 months. Median persistence to ustekinumab had not been reached. Twelve-month persistence to ustekinumab was 82.6% (95% CI 78.1–87.5%). Patients receiving ustekinumab as their first biologic therapy had 12-month persistence of 88.0% (80.8–95.9%) compared to 80.6% (75.0–86.6%) for patients who had previously received other biologic therapies (p=0.059). The adjusted analysis showed a trend to longer persistence for patients receiving ustekinumab as their first biologic therapy compared to biologic experienced patients (HR 1.86 (95% CI 0.95–3.63), p=0.070). Males had higher persistence to ustekinumab than females (HR 0.36 (0.20–0.66), p, Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/e0qOSMerQ_8

Background Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. Aims We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. Methods Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. Results We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. Conclusions Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-06907-5.

Introduction Subsequent lines of subcutaneous tumor necrosis factor alpha inhibitor (SC-TNFi) treatment may be well motivated in the management of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)—collectively named inflammatory arthritis (IA). However, the costs associated with switching SC-TNFis are largely unknown. The objective of this retrospective observational study was to explore costs of healthcare resource utilization (HCRU) associated with switching SC-TNFi treatment among biologic-naïve Swedish patients with IA. Methods Using population-based register data, adult patients filling prescriptions between May 6, 2010 and December 31, 2014 for an SC-TNFi (adalimumab, etanercept, certolizumab, and golimumab) were included. Patients switching treatment (cyclers) were matched to treatment persistent patients on the basis of propensity score and follow-up time. HCRU-associated costs were captured and compared 12 months before and 12 months after the index date (defined as the date of the switch). Results A balanced cohort of 594 matched pairs was derived. Prior to the index date, cyclers had significantly higher non-treatment HCRU costs compared to persistent patients ($3815 [3498–4147] vs. $2900; 95%CI [2565–3256]). However, 12 months after the index date, cyclers had significantly increased their non-treatment HCRU costs while persistent patients lowered theirs ($822 [232–1490] vs. $− 313 [− 664–36]). This resulted in a statistically significant difference in difference of $1135 between the groups. Conclusions In biologic-naïve patients treated with SC-TNFi for IA, cyclers significantly increased their non-treatment HCRU costs 12 months after switching treatment while persistent patients lowered their costs during the same time period. As these findings indicate that differences in treatment persistence may have an impact on costs, further research utilizing more comprehensive data sources in alternate settings is warranted.

Introduction and objective The BELIEVE study is a European, non-interventional study which includes patients with overactive bladder who were prescribed mirabegron as part of routine clinical practice. Data from the Spanish subpopulation has been obtained for the present study, aiming to analyze health-related quality-of-life (HRQoL) and treatment persistence of these patients. Materials and methods Data from 11 Spanish hospitals of the BELIEVE study were analyzed. The primary endpoint was to evaluate change of HRQoL from baseline with overactive bladder questionnaire (OAB-q). Secondary endpoints included treatment persistence, HRQoL based on the EQ-5D-5L questionnaire and adverse events. Study follow-up was 12 months, with two visit windows at 2–4 months and 10–12 months. Results 153 Spanish patients were enrolled in the study. In the Full Analysis Set (FAS), 63.1% were women, and the mean age was 66 years. Symptom bother and HRQoL improved from baseline to 2–4 months and 10–12 months. EQ-5D-5L questionnaire also showed an improved patients’ HRQoL. Treatment persistence was high, as 49% of patients remained with mirabegron at 10–12 months. Adverse events were consistent with previous safety profile results of mirabegron, and no unexpected safety issues were observed. Conclusions Spanish patients treated with mirabegron in real clinical practice reported improvements in HRQoL, with a good tolerability and persistence to treatment.

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA’s Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted. Electronic supplementary material The online version of this article (10.1007/s11239-019-02032-3) contains supplementary material, which is available to authorized users.

Aims To descriptively evaluate treatment persistence among adults who received mirabegron or antimuscarinics in South Korea. Methods This study involved a retrospective analysis of the Health Insurance Review and Assessment (HIRA) database. Patients (≥18 years) who had a new prescription for an overactive bladder (OAB) target medication (mirabegron/antimuscarinic) within an 8-month index period (July 1, 2015-February 29, 2016) were included. The date when the target (index) medication was dispensed was the index date. The 6-month period before the index date was used to assess patient eligibility. A 12-month post-index period was used to assess medication persistence, which was defined as the time to discontinuation. Overall data were analyzed and the results were also stratified by age group (≤65, >65 years), sex, or prior OAB medication experience. Persistence rates were calculated after the 1st, 3rd, 6th, 9th, and 12th months. Results A data set of 52 722 cases was obtained (mirabegron: 11 424, antimuscarinics: 41 298). The mean age was 60.9 ± 16.1 years and the majority of the patients were female (30 862 [58.5%] patients). Median persistence was longer with mirabegron (51 days) versus antimuscarinics (25 days). The persistence rate with mirabegron was higher throughout the study compared with all the antimuscarinics (12-month data: 13.5% and 4.9%, respectively). Longer treatment persistence was noted in older, male, and treatment-experienced patients. Conclusion The results from the HIRA database showed that persistence was longer with mirabegron than with antimuscarinics in South Korea. This finding may help inform clinical decision-making within the South Korean healthcare system.

BACKGROUND: Vedolizumab was shown to be effective and safe for patients with ulcerative colitis (UC) or Crohn's disease (CD) in the GEMINI phase 3 and long-term safety (LTS) studies. AIM: To report treatment persistence and safety results up to 2 years after enrolment in the vedolizumab extended access programme (XAP) METHODS: Vedolizumab XAP is a phase 3b/4, prospective, open-label, multinational, interventional study. At rollover from GEMINI LTS, patients who were experiencing continued clinical benefit with vedolizumab received reduced dosing frequency from every 4 weeks (Q4W) to every 8 weeks (Q8W). Patient persistence on Q8W dosing, incidence of relapse, and safety 2 years after enrolment were investigated. RESULTS: We enrolled 311 patients (142 UC and 169 CD). At baseline, 93.7% (UC) and 89.3% (CD) of patients were in clinical remission; 93.0% (UC) and 84.6% (CD) reduced dosing frequency to Q8W at enrolment. Of those who reduced dosing frequency to Q8W at enrolment, 93.9% (UC) and 91.6% (CD) remained on Q8W dosing; 6.1% (UC) and 8.4% (CD) re-escalated to Q4W dosing. Relapse was reported in 9.1% (UC) and 14.0% (CD) of patients who reduced dosing to Q8W. Adverse events related to vedolizumab were infrequent; no new events were reported. CONCLUSION: We observed high patient persistence on vedolizumab Q8W in the first 2 years after the reduction of dosing frequency in the XAP along with low rates of Q4W dose re-escalation and relapse. The safety profile was consistent with previous reports. ClinicalTrials.gov: NCT02743806. ispartof: ALIMENTARY PHARMACOLOGY & THERAPEUTICS vol:53 issue:2 pages:265-272 ispartof: location:England status: published

ObjectiveTo examine real-world treatment persistence, colectomy-free survival and treatment switching patterns in UK patients with ulcerative colitis (UC) prescribed golimumab or adalimumab.DesignThis was a retrospective chart review study in adult patients diagnosed with UC using data from 16 National Health Service sites in the UK. Patient records were included in the study if they had initiated first or second-line adalimumab or golimumab between 1 March 2016 and 30 September 2017 (index date). Subjects were required for ≥6 months post treatment initiation. Demographics, clinical characteristics, treatment-related data and colectomy data were extracted over a follow-up period of 6–12 months. Treatment persistence rate was the primary outcome. Colectomy-free survival and treatment switching were secondary outcomes. Outcomes were compared between treatments using χ2 tests and Fisher’s exact test for categorical variables. The t-tests were used for continuous variables. Time-to-event variables were evaluated using Kaplan-Meier curves and log-rank tests.ResultsThe study included a total of 183 patients (96 (52.5%) prescribed adalimumab; 87 (47.5%) golimumab), and patients were mostly first line (79.8%). Demographic and clinical characteristics were generally similar between treatment groups. Persistence rates within 12 months were 64.6% for adalimumab and 64.4% for golimumab (p=0.681). Overall, 20.2% switched to other therapy within 1 year, with 8.2% golimumab and 12.0% adalimumab switching to another biologic. Of patients prescribed adalimumab, 14.6% had ≥1 dose change, mainly dose escalations. In the 12 months post treatment initiation, 8.2% of patients underwent colectomy, with no significant difference in colectomy-free survival by treatment, p=0.73.ConclusionThis study provides evidence of clinical outcomes and real-world persistence for adalimumab and golimumab in UC. The persistence rates of both therapies were above 64.0% at 12 months following treatment initiation. In addition, the 1-year colectomy-free survival was relatively similar between the two treatments.

Introduction There are limited real-world data on the prescribing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for patients with type 2 diabetes mellitus (T2DM). Methods This was a retrospective analysis of the CoDiC® database of the Japan Diabetes Clinical Data Management Study Group (JDDM). Demographic and clinical characteristics, concomitant treatment patterns, and GLP-1 RA treatment persistence or modification in patients with T2DM initiating GLP-1 RA therapy were evaluated. Results The analysis included 932 eligible patients with T2DM who had their first GLP-1 RA prescription (index date) between September 2016 and July 2018. Mean age was 63.8 years and 56.0% were male. Most patients had an index GLP-1 RA of dulaglutide (65.7%) or liraglutide (29.1%). Common comorbidities were obesity (58.7%), hypertension (54.7%), dyslipidemia (52.0%), retinopathy (11.3%), and nephropathy (10.2%). Mean hemoglobin A1c (HbA1c) levels decreased from 8.3 to 7.8% over 6 months after GLP-1 RA initiation, and the proportion of patients achieving HbA1c, Plain Language Summary Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are drugs that patients with type 2 diabetes mellitus (T2DM) take to help control their blood sugar levels. In Japan, the GLP-1 RAs that doctors can prescribe are dulaglutide, exenatide, liraglutide, and lixisenatide as of May 2020. We conducted a study of how GLP-1 RAs are used to treat patients with T2DM in Japanese real-world clinical practice. We used a large database of anonymous information from hospitals and clinics in Japan. Over 900 adult patients started their first GLP-1 RA treatment for T2DM between September 2016 and July 2018. Before these patients started GLP-1 RA treatment, many were overweight, had high blood pressure, and had abnormal levels of lipids in their blood. Six months after starting GLP-1 RA treatment, on average these patients had lower hemoglobin A1c (a measure of average blood sugar levels), lower body weight, and better blood lipid levels than before they started GLP-1 RA treatment. Dulaglutide was the most common GLP-1 RA prescribed, then liraglutide. After 6 months, most patients (four-fifths) continued to use their GLP-1 RA treatment without stopping or changing to another treatment. After 18 months, half of the patients were still using their GLP-1 RA. Two-thirds of patients on dulaglutide and one-third of patients on liraglutide continued the treatment after 18 months. This study shows that GLP-1 RAs can benefit patients with T2DM in real-world clinical practice. It also shows that patients may be able to take long-term dulaglutide treatment. Supplementary Information The online version of this article (10.1007/s13300-020-00977-w) contains supplementary material, which is available to authorized users.

Background: Our aim was to follow up patients prescribed lurasidone over 1 year to determine factors predicting treatment persistence. Methods: We used noninterventional, observational, prospective follow up of patients consecutively prescribed lurasidone in a large inner-city NHS mental health trust. We also performed retrospective analysis of outcomes from patient case notes. Results: Data were available for 69 patients consecutively prescribed lurasidone, of whom three (4%) were lost to follow up. Out of the 66 patients not lost to follow-up, 21 (32%) remained on lurasidone at 1 year. The main reasons for discontinuation were perceived ineffectiveness (49% of discontinuers) and adverse effects (36% of discontinuers), whilst a further seven refused all treatment. Median treatment time on lurasidone was 154 days (95% confidence interval (CI), 33–275). Patients who were not treatment-resistant had a substantially reduced risk of discontinuation, relative risk (RR) 0.18 [95% CI 0.08, 0.41, p < 0.001]. Medium doses (>37–74 mg) of lurasidone reduced the risk of discontinuation by 75% [RR 0.25 (95% CI 0.11, 0.58, p = 0.001)]; high doses (>74–148 mg) reduced the risk of discontinuation by 86% [RR 0.14 (95% CI 0.06, 0.35, p < 0.001)]. Risk of discontinuation was approximately doubled when the reason for prescribing lurasidone was poor tolerability of prior treatment [RR 2.01 (95% CI 1.05, 3.85, p = 0.035)]. Conclusion: The likelihood of treatment continuation with lurasidone can be vastly improved by targeting individuals most likely to benefit and by using optimal doses.

Background:Sex-related differences in biologic treatment of psoriatic arthritis (PsA) have been insufficiently studied in a real-world setting.Objectives:To evaluate impact of sex on PsA, treatment effectiveness and persistence after 1 year of biologic treatment.Methods:PsABio (NCT02627768) is a multinational, prospective real-world study in PsA with ustekinumab (UST) or TNF inhibitor (TNFi) as 1st/2nd/3rd-line biologic. Males and females were compared for disease activity and patient-reported outcomes. Descriptive statistics including 95% CI at baseline (BL) and 12 (±3) months (LOCF) follow-up are presented. Intra-sex comparisons between UST and TNFi cohorts were done by logistic regression analysis, with propensity score adjustment for imbalanced BL covariates and non-response imputation for stopping/switching biologic drugs.Results:Among 494 females and 399 males, age and disease duration were similar. However, differences in disease characteristics at BL were considerable: females had worse scores than males for cDAPSA, HAQ-DI, EQ5D VAS, PsAID-12, pain and comorbidities. At 1 year, similar improvements from BL were observed between sexes, but females remained in a worse health state than males (Table). Achievement of composite endpoints MDA (including VLDA) and cDAPSA LDA (including remission) was high overall (38.6% and 61.5%, respectively), but reached by >2-fold and 3-fold more males than females, respectively. HAQ-DI scores remained worse for females at 1 year (0.95) than for males at BL (0.93). Enthesitis resolution was achieved in 46% of females and 75% of males. No significant differences in effectiveness of UST vs TNFi were detected between sexes (Figure). Kaplan–Meier estimated drug persistence was significantly better in males than females (log-rank p=0.0007). There was no intra-sex difference between UST or TNFi in risk of stopping/switching in males or females.Table 1.Patient and disease characteristics at BL and 1-year by sexBL femaleBL male1-year LOCF female1-year LOCF maleBiologic line, %1st4655N/AN/A2nd34333rd2013Co-treatment, %MTX37.434.3N/AN/ACorticosteroids34.632.1NSAIDs59.964.4Antidepressant7.92.5Comorbidities, %N/AN/ACardiovascular69.059.4metabolic syndrome40.131.7Obesity35.223.7Anxiety/depression12.67.5Smoking status, %N/AN/ANever54.941.9Past16.826.6Current22.724.3Unknown5.77.3Joint counts, nSwollen 666.1 (5.4; 6.9)5.6 (4.7; 6.4)2.2 (1.7; 2.6)1.3 (1.0; 1.6)Tender 6813.2 (12.0; 14.4)10.0 (8.9; 11.1)6.0 (5.2; 6.7)3.6 (2.9; 4.3)cDAPSA score, mean (95% CI)cDAPSA, %32.5 (30.5; 34.4)26.9 (24.9; 29.0)15.9 (14.5; 17.2)10.3 (9.0; 11.6)Remission1.0 (0.3; 2.6)4.0 (2.1; 6.7)17.8 (14.1; 22.0)37.7 (32.4; 43.2)Low6.7 (4.4; 9.7)15.0 (11.3; 19.4)33.0 (28.3; 37.9)36.5 (31.3; 42.0)Moderate38.9 (34.0; 44.0)42.6 (37.2; 48.2)34.3 (29.6; 39.2)16.9 (13.0; 21.4)High53.4 (48.2; 58.4)38.3 (33.0; 43.9)14.9 (11.6; 18.9)8.9 (6.0; 12.5)MDA2.3 (1.0; 4.3)7.7 (5.1; 11.2)27.5 (23.1; 32.1)52.2 (46.6; 57.7)VLDA0.00.9 (0.2; 2.6)6.2 (4.1; 9.0)19.7 (15.6; 24.3)HAQ-DI score1.31 (1.25; 1.37)0.93 (0.86; 1.00)0.95 (0.89; 1.02)0.53 (0.47; 0.59)PsAID-12 score6.1 (5.9; 6.3)5.1 (4.9; 5.3)4.0 (3.8; 4.3)2.7 (2.4; 2.9)EQ5D VAS score48.6 (46.6; 50.5)53.8 (51.6; 55.9)59.2 (56.9; 61.4)68.0 (65.5; 70.4)Enthesitis50.7 (45.9; 55.5)48.1 (42.8; 53.3)32.6 (28.3; 37.3)18.0 (14.1; 22.3)Dactylitis15.6 (12.4; 19.3)24.7 (20.4; 29.3)5.7 (3.8; 8.3)4.8 (2.9; 7.4)Data are % (95% CI) unless indicated otherwise. Bold data are significantly different (non-overlapping 95% CI).Conclusion:These real-world data from PsABio on sex differences with biologic treatment suggest that females generally start biologics in a worse PsA state than males. Although treatment improvements were similar between sexes, females remained in worse health at 1 year, and stopped/switched biologic earlier. More comprehensive treatment before severe disease manifestations evolve may improve management in females.Acknowledgements:This study was funded by JanssenDisclosure of Interests:Irene van der Horst-Bruinsma Consultant of: AbbVie, Lilly, MSD, Novartis, UCB, Grant/research support from: AbbVie, MSD, Pfizer, UCB, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Arno Van Kuijk Consultant of: AbbVie, Janssen, LEO Pharma, Novartis, Grant/research support from: Janssen, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Johnson &Johnson, Novartis Galapagos, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared, Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, MSD, Novartis, Pfizer, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Consultant of: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Wim Noel Employee of: Janssen, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Consultant of: AbbVie, AstraZeneca, Lilly, Novartis, Roche, Laure Gossec Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi

Background:There are still unmet needs in the treatment of psoriatic arthritis (PsA), including in terms of treatment persistence, which is a function of effectiveness, safety and patient satisfaction. Ustekinumab (UST) was the first new biologic drug to be developed for the treatment of PsA after tumour necrosis factor inhibitors (TNFi).Objectives:To compare treatment persistence, effectiveness and safety of UST and TNFi in Italian patients within the PsABio cohort.Methods:PsABio (NCT02627768) is an observational study of 1st/2nd/3rd-line UST or TNFi treatment in PsA in 8 European countries. The current analysis set includes 222 eligible patients treated in 15 Italian centres, followed to Month 12 (±3 months). Treatment persistence/risk of stopping was analysed using Kaplan−Meier (KM) and Cox regression analysis. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity Index for PsA (cDAPSA) low disease activity (LDA)/remission were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation of effectiveness endpoints if treatment was stopped/switched before 1 year. Last observation carried forward data are reported.Results:Of patients starting UST and TNFi, 75/101 (74.3%) and 77/121 (63.6%), respectively, persisted with treatment at 1 year. The observed mean persistence was 410 days for UST and 363 days for TNFi. KM curves and PS-adjusted hazard ratios confirmed significantly higher persistence (hazard ratio [95% confidence interval (CI)]) for UST versus TNFi overall (0.46 [0.26; 0.82]; Figure 1). Persistence was also higher for UST than TNFi in patients receiving monotherapy without methotrexate (0.31 [0.15; 0.63]), in females (0.41 [0.20; 0.83]), and in patients with body mass index (BMI) 2 (0.34 [0.14; 0.87]) or >30 kg/m2 (0.19 [0.06; 0.54]). There was no significant difference in persistence between treatments in patients with BMI 25−30 kg/m2. While patients receiving 1st- and 3rd-line UST or TNFi showed similar risk of discontinuation (0.60 [0.27; 1.29] and 0.36 [0.10; 1.25], respectively), patients receiving 2nd-line UST showed better persistence than those receiving 2nd-line TNFi (0.33 [0.13; 0.87]). Other factors added to the PS-adjusted Cox model did not show significant effects. In patients with available follow-up data, the mean (standard deviation) baseline cDAPSA was 26.3 (15.4) for UST and 23.5 (12.3) for TNFi; at 1-year follow-up, 43.5% of UST- and 43.6% of TNFi-treated patients reached cDAPSA LDA/remission. MDA was reached in 24.2% of UST- and 28.0% of TNFi-treated patients, and VLDA in 12.5% of UST- and 10.2% of TNFi-treated patients. After PS adjustment (stoppers/switchers as non-responders), odds ratios (95% CI) at 1 year did not differ significantly between UST and TNFi groups for reaching cDAPSA LDA/remission (1.08 [0.54; 2.15]), MDA (0.96 [0.45; 2.05]) or VLDA (0.98 [0.35; 2.76]). In total, 23 (20.4%) patients reported ≥1 treatment emergent adverse event with UST and 30 (22.2%) with TNFi; 6 (5.3%) and 10 (7.4%) patients, respectively, discontinued treatment because of an adverse event.Conclusion:In the Italian PsABio cohort, UST had better overall persistence compared with TNFi, as well as in specific subgroups: females, patients on monotherapy without methotrexate, with BMI 30 kg/m2, and patients receiving UST as 2nd-line treatment. At 1 year, both treatments showed similar effectiveness, as measured by cDAPSA responses and MDA/VLDA achievement.Acknowledgements:This study was funded by Janssen. Contributing author: Prof. Piercarlo Sarzi-Puttini, ASST Fatebenefratelli-Sacco, University of Milan, ItalyDisclosure of Interests:Elisa Gremese: None declared, Francesco Ciccia Speakers bureau: AbbVie, Abiogen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: Celgene, Janssen, Novartis, Pfizer, Roche, Carlo Selmi Speakers bureau: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Consultant of: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, Giovanna CUOMO: None declared, Rosario Foti Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Marco Matucci Cerinic Speakers bureau: Actelion, Biogen, Janssen, Lilly, Consultant of: Chemomab, Grant/research support from: MSD, Fabrizio Conti Consultant of: AbbVie, Bristol-Myers Squibb, Galapagos, Lilly, Pfizer, Enrico Fusaro Speakers bureau: AbbVie, Amgen, Lilly, Grant/research support from: AbbVie, Pfizer, Giuliana Guggino Speakers bureau: AbbVie, Celgene, Novartis, Pfizer, Sandoz, Grant/research support from: Celgene, Pfizer, Florenzo Iannone Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Andrea Delle Sedie: None declared, Roberto Perricone: None declared, Luca Idolazzi Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Sandoz, Paolo Moscato: None declared, Elke Theander Employee of: Janssen, Wim Noel Employee of: Janssen, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Silvia Marelli Employee of: Janssen, Laure Gossec Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Grant/research support from: AbbVie, AstraZeneca, Lilly, Novartis, Roche.

To study treatment persistence and mortality using a single-pill, fixed-dose combination tablet compared with a two-pill combination for hypertension.We analyzed Australian Pharmaceutical Benefit Scheme records 2011-2014 in a 10% random sample of concessional patients prescribed concomitant amlodipine and perindopril - either as a single-pill, fixed-dose combination tablet (n = 9340) or as two-pill combination therapy (n = 3093). Main outcome measures were: (a) proportions failing to continue amlodipine + perindopril over time, (b) proportions failing to continue any subsequent calcium channel and angiotensin inhibition therapy over time and (c) proportions dying.After 12 months, 34% of single-pill and 57% of two-pill users discontinued amlodipine + perindopril, median persistence time 42 months versus 7 months; 28% and 47% respectively discontinued any calcium channel-angiotensin inhibition therapy. After 48 months, 8% of single-pill and 18% of two-pill users had died. In a multivariate model adjusted for age, gender, duration and intensity of prior hypertension therapy, initial dose of amlodipine and perindopril, diabetes, hyperlipidemia, and complexity of care, the hazard ratio for risk of discontinuation over 42 months in the two-pill versus single-pill amlodipine + perindopril group was 1.94 (95% CI 1.83-2.06). The hazard ratio for discontinuation in two-pill versus single-pill users of any calcium channel-angiotensin inhibition therapy was 1.86 (1.74-1.99). The adjusted hazard ratio for risk of death over 48 months was 1.83 (1.55-2.16), but the mortality outcome may be an overestimate due to residual confounding.Use of a single-pill, fixed-dose combination in hypertension is associated with superior persistence and reduced mortality compared with use of two pills, suggesting a higher priority for the use of fixed-dose combinations.

Purpose In immune-mediated rheumatic diseases (IMRDs), persistence to treatment may be used as a surrogate marker for long-term treatment success. In previous comparisons of persistence to tumor necrosis factor α inhibitors (TNFis), a paucity of data for subcutaneous (SC) golimumab was identified. The aim of this study was to conduct a systematic review of persistence to SC golimumab in clinical practice and contextualize these data with five-year persistence estimates from long-term open-label extension (OLE) trials of SC TNFis in IMRDs. Patients and methods PubMed, Embase, MEDLINE, and conference proceedings from European League Against Rheumatism (EULAR), American College of Rheumatology (ACR), and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) were searched. All studies on patients treated with SC golimumab for IMRD were included if they reported data on the persistence to golimumab. Results Of 376 available references identified through the searches, 12 studies with a total of 4,910 patients met the inclusion criteria. Furthermore, nine OLE trials were available. Among the included studies from clinical practice, at six months, one year, two years, and three years, the proportion of patients persistent to treatment ranged from 63% to 91%, 47% to 80%, 40% to 77%, and 32% to 67%, respectively. In the four studies that included comparisons to other biologics, golimumab was either statistically noninferior or statistically superior to other treatments, an observation that was supported by indirect comparisons of unadjusted point estimates of OLE trials. Conclusion The data reviewed in this study indicate that golimumab may have higher persistence than other TNFis, a notion that is supported by indirect comparisons of persistence data from OLEs of randomized controlled trials (RCTs). Furthermore, the study suggests that persistence may be lower in biologic-experienced compared with biologic-naive patients and higher in axial spondyloarthritis compared with rheumatoid arthritis and psoriatic arthritis.

Model-based economic evaluation was performed to assess the cost-effectiveness of zoledronic acid. Although zoledronic acid was dominated by alendronate, the incremental quality-adjusted life year (QALY) was quite small in extent. Considering the advantage of once-yearly injection of zoledronic acid in persistence, zoledronic acid might be a cost-effective treatment option compared to once-weekly oral alendronate. The purpose of this study was to estimate the cost-effectiveness of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan. A patient-level state-transition model was developed to predict the outcome of patients with osteoporosis who have experienced a previous vertebral fracture. The efficacy of zoledronic acid was derived from a published network meta-analysis. Lifetime cost and QALYs were estimated for patients who had received zoledronic acid, alendronate, or basic treatment alone. The incremental cost-effectiveness ratio (ICER) of zoledronic acid was estimated. For patients 70 years of age, zoledronic acid was dominated by alendronate with incremental QALY of −0.004 to −0.000 and incremental cost of 430 USD to 493 USD. Deterministic sensitivity analysis indicated that the relative risk of hip fracture and drug cost strongly affected the cost-effectiveness of zoledronic acid compared to alendronate. Scenario analysis considering treatment persistence showed that the ICER of zoledronic acid compared to alendronate was estimated to be 47,435 USD, 27,018 USD, and 10,749 USD per QALY gained for patients with a T-score of −2.0, −2.5, or −3.0, respectively. Although zoledronic acid is dominated by alendronate, the incremental QALY is quite small in extent. Considering the advantage of annual zoledronic acid treatment in compliance and persistence, zoledronic acid may be a cost-effective treatment option compared to alendronate.

Background Vedolizumab (VDZ) is increasingly being positioned as first-line biologic therapy for the treatment of inflammatory bowel disease (IBD) in adults, particularly for ulcerative colitis (UC). Identifying a certain subset of bio-naïve UC patients most likely to benefit from VDZ and remain on long-term maintenance therapy is important. The purpose of this study was to evaluate predictors of VDZ treatment persistence at 12 months in real-world clinical practice. Methods We performed a retrospective review of all adult (≥18 years) bio-naïve UC patients started on VDZ at US gastroenterology physician office infusion centres. Data collection included baseline demographics, VDZ therapy, concomitant oral agents, disease severity, and disease activity scores using the partial Mayo score (pMayo). Disease severity was characterised by prior IBD-related surgery and IBD-related healthcare resource utilisation within 1 year of VDZ initiation. Clinical response was assessed at baseline, 6 weeks, and 14 weeks and defined as a pMayo reduction of ≥2 points. Patients were divided into two cohorts, those persisting on VDZ at 12 months and those discontinuing VDZ prior to 12 months. Logistic regression analysis was used to determine predictors associated with persistence. Results A total of 141 UC patients receiving VDZ as first-line biologic therapy were identified: mean age 44 ± 14.5 years, male gender 82 (58%), median disease duration 5.5 (IQR 1.6–13.3) years. VDZ treatment persistence at 12 months was observed in 102 (72%) patients (Figure 1). The remaining 39 patients discontinued VDZ within the first 12 months. Amongst those who discontinued VDZ, reasons included lack or loss of response in 35 (90%), antibodies in 3 (8%), and intolerance in 1 (3%). In the logistic regression analysis, the only factor associated with VDZ treatment persistence was clinical response at 14 weeks (OR 6.5 [95% CI 2.9–14.5]). No other variables (age, gender, smoking status, disease duration, concomitant oral agents, or severity of illness) influenced persistence at 12 months. Conclusion Almost three-fourths of bio-naïve UC patients treated with vedolizumab experienced treatment persistence at 12 months. Our data suggest that response to induction may be used to predict those who will remain on maintenance therapy.

Background Vedolizumab, a gut-selective, α 4β 7 integrin antagonist, has been established as an effective and safe treatment for patients with UC or CD in the GEMINI phase 3 program and long-term safety (LTS) study. An extended access program (XAP) was initiated to provide continued access to patients who were benefiting from vedolizumab in GEMINI LTS and to monitor safety. We now report persistence and safety results from a 2-year data analysis. Methods Vedolizumab XAP (NCT02743806) is a phase 3b/4 prospective, open-label, multinational interventional study. A rollover from GEMINI LTS (NCT00790933) to the XAP, patients reduced dosing frequency from vedolizumab 300 mg IV every 4 weeks (Q4W) to every 8 weeks (Q8W) or remained on vedolizumab 300 mg IV Q4W if medically indicated. This 2-year data analysis assessed persistence on Q8W dosing after dosing frequency reduction, need for escalation to Q4W dosing, incidence of relapse (defined as dose escalation, study withdrawal due to adverse event, loss of adequate benefit from vedolizumab, or increased corticosteroid [CS] or immunomodulator dose), and safety 2 years after rollover from GEMINI LTS. Results A total of 311 patients (142 UC, 169 CD) from GEMINI LTS enrolled in the XAP. Median (range) duration of exposure to vedolizumab prior to the XAP was 8.0 years (5.2–10.0) for patients with UC and 7.5 years (5.4–9.9) for patients with CD. Of patients with UC and CD, 93.0% and 84.6%, respectively, reduced dosing frequency to Q8W at XAP start, and 87.3% and 77.5%, respectively, remained on Q8W after 2 years. At baseline, 93.0% of all patients with UC and 88.2% of all patients with CD were in CS-free remission; patients who maintained Q4W dosing at baseline had lower CS-free remission rates (62.5% in UC and 69.2% in CD). Of patients who initiated Q8W dosing at enrolment in the XAP, 95% had no relapse for ≥6 months (97.0% UC, 93.7% CD; Table 1). Only 7.3% of patients required dose escalation to Q4W, and 11.6% experienced relapse during the 2-year follow-up. Times to dose escalation and relapse were similar in patients with UC and CD (Figures 1 and 2). At 2 years, 4 of 8 patients with UC and 4 of 12 patients with CD who required dose escalation to Q4W discontinued vedolizumab early due to loss of benefit or adverse events. Adverse events related to vedolizumab were infrequent; no new or serious events attributed to vedolizumab were reported. Conclusion High patient persistence on Q8W vedolizumab was observed in the first 2 years after reduction of dosing frequency in the XAP. Overall, there were low rates of Q4W dose escalation and CD or UC disease relapse. The safety profile was consistent with previous reports with no new signals observed.

Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called “needle fatigue”, i.e., a waning commitment to continue with the prescribed injectable treatment. Therefore, alternative treatment strategies to enhance patients’ adherence are warranted. In this independent, multicentre post-marketing study, we sought to directly compare switching to either teriflunomide (TFN), dimethyl fumarate (DMF), or pegylated interferon (PEG) on treatment persistence and time to first relapse over a 12-month follow-up. We analyzed a total of 621 patients who were free of relapses and gadolinium-enhancing lesions in the year prior to switching to DMF (n = 265), TFN (n = 160), or PEG (n = 196). Time to discontinuation and time to first relapse were explored in the whole population by Cox regression models adjusted for baseline variables and after a 1:1:1 ratio propensity score (PS)-based matching procedure. Treatment discontinuation was more frequent after switching to PEG (28.6%) than DMF (14.7%; hazard ratio [HR] = 0.25, p

The purpose of this study is to provide detailed data on treatment persistence and clinical outcomes in Chinese patients with nonvalvular atrial fibrillation (NVAF). A single-center retrospective observational study was conducted. A total of 26,663 NVAF patients were enrolled from January 1, 2014 to December 31, 2017, clinical information of whom were from inpatient and outpatients data system was collected. The 1-year treatment persistence rates of 11,350 dabigatran users were 24.5% in 2014, 36.6% in 2015, 37.7% in 2016 and 51.8% in 2017. The predominant reason of non-persistence patients was the cost of treatment. Incidence rates of all-cause death, ischemic stroke and embolism were 1.99/100 person-years, 2.56/100 person-years and 0.77/100 person-years, respectively. Incidence rates of minor bleeding events, intracranial hemorrhage and gastrointestinal hemorrhage were 10.05/100 person-years, 0.51/100 person-years and 0.85/100 person-years, respectively. In conclusion, it is of importance for Chinese clinicians to know about these information because dabigatran is a relatively new drug in China. Compared with other reported data, patients of this study have (1) lower dabigatran persistence and lower incident rates of all-cause death, systemic embolism, minor bleeding events and gastrointestinal hemorrhage and (2) higher incident rates of ischemic stroke and intracranial hemorrhage.

Neurogenic orthostatic hypotension (nOH) is a subtype of orthostatic hypotension (OH) observed in the presence of neuropathy and is associated with increased risk of falling, impaired function, and poor quality of life. Droxidopa and midodrine are approved in the United States to treat symptomatic nOH and OH in adults, respectively. In this study, we compared the treatment persistence of droxidopa and midodrine.A retrospective analysis of patients prescribed either droxidopa or midodrine was conducted using the Symphony Health Solutions database (Symphony Health Solutions, Phoenix, AZ, USA). Inclusion criteria were (1) a pharmacy insurance claim in at least 16 consecutive quarters from mid-2014 to 2018 and (2) an active prescription for droxidopa or midodrine of ≥30 days' duration during that period. Treatment persistence was defined as the time to the first break in drug coverage of ≥45 days and was capped at 365 days.Data from 2305 patients who received droxidopa and 117,243 patients who received midodrine were included in this analysis. Median (95% CI) treatment persistence was significantly longer in the droxidopa cohort versus the midodrine cohort (303 [274-325] vs 172 [169-176] days; P 0.001). After adjustment for confounding factors, patients using droxidopa monotherapy (i.e., without any concomitant midodrine and/or fludrocortisone use) were 16% more likely to be persistent at any time point than patients using midodrine (P 0.001).In this real-world data analysis, patients using droxidopa without concomitant medications for OH were more likely to remain on treatment than patients on midodrine.

BACKGROUND: Data from trials of vedolizumab for inflammatory bowel disease and from real-world studies suggest an exposure-response relationship, such that vedolizumab trough levels may predict clinical and endoscopic outcomes. OBJECTIVE: The purpose of this study was to evaluate in a prospective observational study the utility of an early vedolizumab trough level assay for predicting the first-year vedolizumab therapy outcome. METHODS: This prospective observational study included consecutive inflammatory bowel disease patients. We measured vedolizumab trough levels and anti-vedolizumab antibodies at weeks 6 and 14. Clinical outcome was assessed at weeks 6, 14, 22 and 54. The primary endpoint was the correlation between early vedolizumab trough levels and vedolizumab persistence over the first year of treatment, defined as the maintenance of vedolizumab therapy due to sustained clinical benefit. RESULTS: We included 101 patients initiating vedolizumab. A cut-off vedolizumab trough level of 16.55 µg/ml at week 14 predicted vedolizumab persistence within the first year of therapy, with 73.3% sensitivity and 59.4% specificity (p = 0.0009). Week 14 vedolizumab trough level was significantly higher in patients with clinical remission at weeks 14, 22 and 54; and in patients achieving mucosal healing within 54 weeks. CONCLUSION: High vedolizumab trough level at week 14 was associated with a higher probability of maintaining vedolizumab therapy over the first year due to sustained clinical benefit.

Discrepancies are seen between arguments in favor of and against prescribing generic versus brand-name drugs.To provide real-world evidence on treatment persistence, economic and clinical outcomes of pregabalin, generic versus brand-name (Lyrica®, Pfizer), routinely used to treat neuropathic pain (NP) or generalized anxiety disorder (GAD).Electronic medical records from subjects' first starting treatment with pregabalin between January-2015 and June-2016 were analyzed. Persistence, resources utilization, and costs were assessed, along with remitter and responder rates.A total of 4860 records were analyzed. Discontinuation was lower with brand-name than with generic in NP (adjusted hazard ratio [HR]: 0.70 [95% CI: 0.58-0.85], p 0.001) and GAD patients (HR: 0.63 [0.45-0.84], p 0.001). Adjusted mean total costs were lower with brand-name: €1500 [1428-1573] vs. €2003 [1864-2143] in NP and €1528 [1322-1734] vs. €2150 [1845-2454] in GAD (both p 0.001). More patients were remitters/ responders with brand-name in NP (55.0% vs. 46.7% and 59.2% vs. 48.4%, respectively; p 0.001) and GAD (58.6% vs. 48.7% and 64.6% vs. 47.2%, respectively; p 0.001).As a consequence of higher persistence in routine practice, patients who first started therapy with pregabalin brand-name versus generic showed better pain or anxiety outcomes at a lower cost to payers in Spain.

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment. Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation. Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months. Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA.

Mustafa Acar,1 Prabhjot Juneja,2 Malcolm Handel1 1Janssen-Cilag Pty Ltd, Sydney, NSW, Australia; 2Prospection Pty Ltd., Sydney, NSW, Australia Introduction: To describe the persistence of treatment with subcutaneous tumor necrosis factor inhibitors (TNFi) adalimumab, etanercept, and golimumab in immune-mediated rheumatic disease (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) by treatment sequence (first-line treatment, second-line or further lines of treatment). Methods: A retrospective cohort analysis was conducted using the Australian Commonwealth Department of Human Services Pharmaceutical Benefits Scheme 10% sample data from January 1, 2010, to June 30, 2016. Pharmaceutical Benefits Scheme indications were used to identify patient prescriptions for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A patient was considered persistent until a 3-month gap period where a prescription was not dispensed. The 3-month gap interval was chosen because only 1% of all discontinuations occurred beyond this 3-month period. Results: Data from 2,612 first-line patients were included. Treatment discontinuation among first-line patients treated with etanercept or adalimumab was not significantly different from those treated with golimumab (HR 1.10, 95% CI 0.95–1.28, P=0.22; HR 1.06, 95% CI 0.93–1.22, P=0.39; respectively). Among the 1,276 patients in the second-line cohort (etanercept=41%, adalimumab=41%, golimumab=18%) discontinuation was significantly higher for patients on etanercept compared with golimumab (HR 1.24, 95% CI 1.03–1.50, P=0.03); but not for adalimumab compared with golimumab (HR 1.11, 95% CI 0.91–1.34, P=0.31). In the third-line setting, treatment persistence with etanercept was longer than golimumab (HR 0.75, 95% CI 0.59–0.96, P=0.02), but there was no difference between golimumab and adalimumab. Similar findings occurred in the propensity score matched population. Conclusion: Our study shows there is variance in real-world persistence to TNFi in patients with immune-mediated rheumatic disease by line of therapy, with the time on therapy decreasing by line. Australian persistence has been reported at lower overall rates than international evidence. Keywords: tumor necrosis factor inhibitors, arthritis, psoriatic, rheumatoid arthritis, ankylosing spondylitis, treatment persistence

Background Persistence on-treatment with antimuscarinics in patients with overactive bladder (OAB) is reported to be sub-optimal. This retrospective, longitudinal, observational cohort study assessed treatment persistence with β3-adrenoceptor agonists (i.e. mirabegron) and antimuscarinics, both classes of OAB pharmacotherapy, in patients with OAB in Spain. Methods Adults who received mirabegron or an antimuscarinic in routine clinical practice (1 June–31 October 2014), were identified from anonymised prescription data within the Spanish Cegedim Electronic Medical Records database. The primary endpoint, treatment persistence (time to treatment discontinuation [TTD] and the proportion of patients remaining on-treatment after 12 months), was unadjusted for potential confounders. Multivariate Cox regression models of persistence, adjusted for baseline characteristics, were used to compare differences in treatment groups. Adjusted subgroup analyses (target OAB drug, age, treatment status and sex) and sensitivity analyses (extending the time used to define treatment discontinuation from 30 days [base-case] to 45, 60 or 90 days without prescription renewal) were also performed. Results Overall, 1798 patients received mirabegron (N = 1169) or an antimuscarinic (N = 629); the mean age was 66.42 years. Median TTD was longer for mirabegron versus antimuscarinics (90 vs 56 days) and a higher proportion of patients who received mirabegron were persistent after 12 months (20.2% vs 10.2%); multivariate analyses indicated significantly greater persistence with mirabegron versus antimuscarinics (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.37–1.70; p

summaryThe effectiveness and safety of dabigatran for stroke prevention in atrial fibrillation (SPAF) demonstrated in RE-LY needs to be confirmed in daily care. To evaluate treatment persistence, effectiveness and safety of dabigatran therapy in SPAF patients in daily care, we used data from an ongoing, prospective, non-interventional registry of more than 2,500 patients on novel oral anticoagulants in daily care. Between October 1, 2011 and February 28, 2013, a total of 341 SPAF patients receiving dabigatran were enrolled. The combined endpoint of stroke/transient ischaemic attack/systemic embolism occurred at a rate of 2.93/100 patient-years in the intention-to-treat analysis (95%-CI 1.6–4.9) and at 1.9/100 patient-years in the on treatment analysis (events within three days after last intake). On-treatment rates were higher in patients selected for 110 mg dabigatran (n=183) BID compared to the 158 patients selected for 150 mg BID (2.88 [95% CI 1.16–5.93] vs 0.86/100 patient-years [95% CI 0.10, 3.12]). On treatment, major bleeding occurred at a rate of 2.3/100 patient-years and numerically more often in patients receiving the 110 mg BID dose compared to the 150 mg BID dose (2.9 vs 1.7/100 patient-years). Dabigatran treatment discontinuation occurred in a total of 124 patients during follow-up (25.8 per 100 patient-years in Kaplan Meier analysis). Main reasons for treatment discontinuation were nonbleeding side effects. Our data contribute to the confirmation of effectiveness and relative safety of dabigatran in unselected patients in daily care. However, discontinuation rates are not lower than those reported for patients treated with vitamin K antagonists.

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla-100) or insulin detemir (DET) with ≥1 A1C measurement during 12-month baseline and 18-month follow-up periods were included. Patients with a refill gap of >90 days were considered non-persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow-up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non-persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.

Background: To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. Methods: In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. Results: A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. Discussion: This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics. Conclusions: Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.

Background Many patients with acromegaly require medical treatment that includes somatostatin analogs (SSAs). Long-acting SSA formulations are widely used, due in part to increased patient convenience and increased treatment adherence vs daily medications. Although medication compliance can be poor in patients with chronic conditions, adherence and persistence with these SSAs in patients with acromegaly has not been evaluated. This analysis utilized claims data to estimate treatment adherence and persistence for lanreotide depot and long-acting octreotide in this population. Methods This retrospective analysis used the MarketScan® database (~100 payors, 500 million claims in the US), which was searched between January 2007 and June 2012 to identify patients with acromegaly taking either lanreotide depot or long-acting octreotide. Patients switching treatments were excluded. Treatment adherence was assessed using medication possession ratio (MPR; number of doses dispensed in relation to dispensing period; ≥80% is considered adherent), injection count, and treatment time. Persistence was estimated by Kaplan-Meier analyses and Cox proportional hazards modeling. A washout period, defined as no acromegaly-related prescription activity 180 days prior to the index date, was employed to minimize effects of prior therapy and focus on patients more likely to be treatment-naïve. Results Altogether 1308 patients with acromegaly receiving a single SSA for treatment (1127 octreotide, 181 lanreotide) who had not switched treatments were identified. Mean MPR in patients with a 180-day washout (n = 663) was 89% for those receiving octreotide (n = 545) and 87% for those receiving lanreotide (n = 118). Median number of days on therapy was 169 (95% CI 135–232) for octreotide patients and 400 (95% CI 232–532) for lanreotide patients. The point estimate of the Cox proportional hazard ratio for stopping treatment was 1.385 for octreotide vs lanreotide (95% CI 1.079–1.777), suggesting a 38.5% increased risk for stopping octreotide before lanreotide. Conclusions Treatment adherence was similarly good for both injectable SSA treatments studied, at 87% or greater. Persistence was greater with lanreotide than octreotide and the risk of discontinuing therapy was lower with lanreotide than octreotide. Further studies to determine factors leading to these differences in persistence or to predict discontinuation of therapy may aid in clinical management of these patients.

Background Limited studies have evaluated the medication-taking behavior in very elderly hypertensive patients. The aim of this study was to evaluate the persistence and adherence with antihypertensive agents in treatment-naïve patients, along with other related factors, according to age. Methods Adult (19–64 years), elderly (65–79 years), and very elderly (≥80 years) uncomplicated hypertensive patients starting antihypertensive monotherapy were identified from the National Health Insurance claims database. The first-year treatment persistence and adherence rates measured using the medication possession ratio were assessed and compared in these three age cohorts. Results After propensity score matching, three age cohorts with 6689 patients each were assembled from 228,925 uncomplicated hypertensive patients who began antihypertensive monotherapy in 2012. The treatment persistence and adherence rates over the first year were the lowest in the very elderly (59.5% and 62.8%, respectively) and highest in the elderly (65.2% and 67.9%, respectively) patients among the three age cohorts (p

The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity.

Objective: To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. Methods: Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. Result: Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. Conclusion: After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity. Refereed/Peer-reviewed

ObjectivesTo summarise real-world data from studies reporting golimumab persistence in European immune-mediated rheumatic disease (IMRD) populations and to report pooled estimates.DesignSystematic literature review.Data sourcesRelevant literature was identified through searching Medline and Embase via Ovid as well as the conference databases of European League Against Rheumatism and American College of Rheumatology—Association of Rheumatology Health Professionals.Eligibility criteriaWe screened records using predefined patients, interventions, comparators, outcomes and study design criteria. Eligible studies included reports of persistence among adult IMRD patients in Europe receiving treatment with subcutaneous golimumab. Clinical trials, randomised controlled trials, literature reviews, editorials, guidelines and studies with Data extraction and synthesisFollowing double screening by two independent reviewers, 27 studies out of 578 identified records were selected for inclusion and subsequent data extraction. Persistence was most commonly reported at 12and 24 months; hence, pooled persistence estimates were calculated for these two time points and reported according to indication.ResultsPersistence ranged between 58.1% (psoriatic arthritis (PsA) patients regardless of treatment line) and 75.7% (biological-naïve rheumatoid arthritis patients) at 12 months; at 24 months, the range was 43% (axial spondyloarthritis (AxSpA) patients regardless of treatment line) and 69.6% (biological-naïve PsA patients). On the basis of data from 12 studies, persistence with golimumab treatment was either significantly higher or not significantly different from other tumour necrosis factor inhibitors (TNFi).ConclusionsGolimumab persistence at 24 months approximates 50%, with a lower persistence among AxSpA (43%) patients. However, as the number of studies in these populations was low, they warrant further research. In 12 studies comparing various TNFi treatments, golimumab was shown to have significantly better or equal persistence to its comparators.

Supplemental Digital Content is available in the text, Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK. To describe real-world early experiences of vedolizumab to treat CD and UC in the UK. A retrospective, chart review study of patients with CD or UC treated with vedolizumab across 5 UK hospitals. All eligible adults (≥18 years at initiation) with a diagnosis of CD and ≥14 weeks of data or UC and ≥10 weeks of data available following vedolizumab initiation were included. Data were analyzed for 112 patients (CD: 66; UC: 46). Patients with CD had a median of 7.4 (interquartile range 5.7–9.4) months follow-up and patients with UC had a median of 7.4 (5.6–10.2) months follow-up post-vedolizumab initiation. Most patients, 80% (53/66) with CD and 89% (41/46) with UC, remained on vedolizumab treatment at the time of data collection. No new safety signals were identified during the study. These results add to the body of evidence supporting vedolizumab as an effective and well-tolerated treatment for CD and UC in real-world clinical practice.

Raymond Miao,1 Wenhui Wei,1 Onur Baser,2,3 Lin Xie2 1Sanofi US, Bridgewater, NJ, USA; 2STATinMED Research, Ann Arbor, MI, USA; 3Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA Introduction: Patients with type 2 diabetes mellitus (T2DM) often require intensification of basal insulin therapy. This retrospective, observational study compared real-world outcomes in US patients with T2DM treated with insulin glargine who added a rapid-acting insulin (RAI) (basal–bolus approach) with those who switched to premixed insulin (PMX). Methods: The national US IMPACT® database was used to identify data from adult patients (≥18 years of age) with T2DM who added bolus RAI to insulin glargine (GLA + RAI) or who switched from GLA to PMX between 2001 and 2009. A stringent 1:1 propensity score-matching method was used to address the selection bias by matching GLA + RAI patients and PMX patients. Clinical and economic outcomes were determined for 1 year after the initial pharmacy claim for RAI or for PMX. Outcomes included treatment persistence and adherence, average insulin doses, glycated hemoglobin (A1C) levels, the prevalence and incidence of hypoglycemia, and health care costs/utilization. Analysis was carried out using an intent-to-treat approach. Results: The study included data from 746 propensity-matched patients (n = 373 in each cohort). Treatment persistence and adherence were higher in the GLA + RAI cohort. There was no significant difference in A1C reduction from baseline and the number of patients achieving target A1C levels of

Background Anti-parathyroid treatment initiation and discontinuation are important decisions in chronic haemodialysis (HD) patients, where pill burden is often excessive. The present study aimed to describe secondary hyperparathyroidism (sHPT) drug therapy changes in HD patients. Methods Retrospective observational cohort study of incident European HD patients with sHPT who were prescribed calcitriol or alfacalcidol (alpha calcitriol), paricalcitol or cinacalcet. Results Treatment-naive patients prescribed alpha calcitriol (N = 2259), paricalcitol (N = 1689) and cinacalcet (N = 1245) were considered for analysis. Serum intact parathyroid hormone (iPTH) levels decreased post-initiation with all treatment modalities; serum calcium and phosphate levels increased in response to activated vitamin D derivatives but decreased with cinacalcet. Approximately one-third of alpha calcitriol and paricalcitol patients but less than one-quarter of cinacalcet patients discontinued treatment. Although the three groups had comparable serum iPTH control at the time of treatment discontinuation, they differed in terms of calcium and phosphate levels. Following discontinuation, the evolution of laboratory parameters differed by treatment modality: whilst iPTH increased for all three treatment groups, calcium and phosphate decreased in patients who were being treated with alpha calcitriol and paricalcitol at the time of discontinuation, and increased in those who had been treated with cinacalcet. Conclusions In conditions of daily clinical practice, attaining and maintaining recommended biochemical control of sHPT appears to be more frequently achievable with cinacalcet than with activated vitamin D compounds.