Higher Treatment Persistence Research Articles

Efficacy and Safety of Elective Switching from Intravenous to Subcutaneous Infliximab [CT-P13]: A Multicentre Cohort Study.

BackgroundIntravenous [IV] infliximab is a well-established therapy for inflammatory bowel diseases [IBD] patients. A subcutaneous [SC] formulation of infliximab [CT-P13] has recently been shown to be as effective as IV infliximab after two doses of IV induction in a randomised trial, but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching programme to SC CT-P13 in patients treated with IV infliximab.MethodsPatients on established maintenance IV infliximab, who switched to SC CT-P13, were included in this retrospective multicentre cohort study. Disease activity was monitored serially with the Harvey-Bradshaw Index [HBI] for Crohn’s disease [CD] and the Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis (UC) for up to 12 months at months 3, 6, and 12. Faecal calprotectin [FC] and C-reactive protein [CRP] were recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6, and 12 following switch. The primary outcome measure was treatment persistence at latest follow-up. Secondary outcome measures included infliximab pharmacokinetics [PK], safety, need for corticosteroid rescue therapy, and need for surgery.ResultsWe included 181 patients, of whom 115 [63.5%] had CD. The majority [72.4%] were on 8-weekly dosing of intravenous infliximab prior to switching, and more than half [59.1%] were on concomitant immunomodulatory therapy. The majority of patients (CD: 106, 92.2%; UC: 46, 76.7%; and IBD unclassified [IBD-U]: 5, 83.3%) were in clinical remission. Treatment persistence rate was high [n = 167, 92.3%] and only 14 patients [7.7%] stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6, or 12 months for HBI, SCCAI, CRP, or FC. Of the total cohort, 25 patients (13.8%) had perianal CD. Of these, only two patients [8%] had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia [EUA]. Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl [range 0.4-16] to 16.0 µg/dl [range 2.3-16, p <0.001] at 3 months. Serum levels stayed stable at 6 months [median 16 µg/dl, range 0.3-17.2] and 12 months [median 16 µg/dl, range 0.3-19.1, both p <0.001 compared with baseline]. Among the variables examined, only antibodies to infliximab [ATI] was associated with infliximab levels (odds ratio [OR] -13.369, 95% CI -15.405, -11.333, p <0.001]. A total of 14 patients [7.7%] developed ATI; of these, nine [64.3%] were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI [p = 0.15]. In a subset of patients receiving escalated IV infliximab dosing frequency prior to switching, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high.ConclusionsAmong patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity, with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13, and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.

Long-term Persistence of First-line Biologics for Patients With Psoriasis and Psoriatic Arthritis in the French Health Insurance Database

Treatment options for psoriasis (PsO) and psoriatic arthritis (PsA) have evolved significantly throughout the era of biologics. Clinical trials are inadequate to assess the relative long-term efficacy of biologics and are often insufficient regarding safety. To assess the long-term persistence of different biologic classes to treat PsO and PsA. This nationwide cohort study involved the administrative health care database of the French health insurance scheme linked to the hospital discharge database. All adults with PsO and PsA who were new users of biologics (not in the year before the index date) from January 1, 2015, to May 31, 2019, were included and followed up through December 31, 2019. Patients hospitalized for PsA in the PsO cohort and for PsO in the PsA cohort in the year before the index date were excluded. Data were analyzed from June 1 to October 31, 2021. Persistence was defined as the time from biologic therapy initiation to discontinuation and was estimated using the Kaplan-Meier method. Comparison of persistence by biologic class involved using propensity score-weighted Cox proportional hazards regression models and adjustment on specific systemic nonbiologics (time-dependent variables). A total of 16 892 patients with PsO were included in the analysis (mean [SD] age, 48.5 [13.8] years; 9152 men [54.2%] men). Of these, 10 199 patients (60.4%) started therapy with a tumor necrosis factor (TNF) inhibitor; 3982 (23.6%), with an interleukin 12 and interleukin 23 (IL-12/23) inhibitor; and 2711 (16.0%), with an interleukin 17 (IL-17) inhibitor. An additional 6531 patients with PsA (mean [SD] age, 49.1 [12.8] years; 3565 [54.6%] women) were included; of these, 4974 (76.2%) started therapy with a TNF inhibitor; 803 (12.3%), with an IL-12/23 inhibitor; and 754 (11.5%), with an IL-17 inhibitor. Overall 3-year persistence rates were 40.9% and 36.2% for PsO and PsA, respectively. After inverse probability of treatment weighting and adjustment, the IL-17 inhibitor was associated with higher persistence compared with the TNF inhibitor for PsO (weighted hazard ratio [HR], 0.78 [95% CI, 0.73-0.83]) and PsA (weighted HR, 0.70 [95% CI, 0.58-0.85]) and compared with the IL-12/23 inhibitor for PsA (weighted HR, 0.69 [95% CI, 0.55-0.87]). No difference between the IL-17 inhibitor and IL-12/23 inhibitor for PsO was noted. The IL-12/23 inhibitor was associated with higher persistence than the TNF inhibitor for PsO (weighted HR, 0.76 [95% CI, 0.72-0.80]), with no difference observed for PsA. The findings of this cohort study suggest that IL-17 inhibitors are associated with higher treatment persistence than the TNF inhibitor for PsO and PsA. Interleukin 17 inhibitors were also associated with higher persistence than the IL-12/23 inhibitor for PsA, with no difference for PsO. However, the persistence rates of all biologics remained globally low at 3 years.

P267 Sequencing of anti-TNF agents and gut-selective anti-lymphocyte trafficking (GSALT) therapy in the treatment of Crohn’s disease (CD)

Abstract Background Anti-TNF agents and GSALT therapy (MAdCAM α4β7 blocker) are available treatment options for patients (pts) with moderate-to-severe CD. There are limited data on the optimal sequencing of these two mechanisms of action (MOAs) from the first line (1L) to second line (2L) biologic treatment of CD to inform clinician’s decision making. Methods This retrospective study used the Truven Health MarketScan administrative claims database to assess treatment pathways in a large U.S. insured population. Biologic naïve adult CD pts (identified using ICD-9 and 10 codes) who initiated (date of initiation defined as an index date) 1L biologic treatment (adalimumab [ADA], infliximab [IFX], certolizumab pegol [CTZ], or vedolizumab [VDZ] between 09/2016 and 09/2019) with at least 6 months of continuous health benefits enrolment post biologics initiation were included. Pts treated with biologics of different MOAs in 1L and 2L setting were identified to evaluate the treatment sequencing of either VDZ to anti-TNF or anti-TNF to VDZ. Treatment persistence was defined as time to index drug discontinuation with a pre-defined gap or switch to other biologic drugs. Results In the 1L, 474 VDZ and 4173 anti-TNF (2648 ADA, 1446 IFX, and 79 CTZ) pts were included. Among the 1L VDZ pts, only 33 switched to anti-TNF as 2L biologic treatment (VDZ to anti-TNF). Among the 1L anti-TNF pts, 221 switched to VDZ as 2L biologic therapy (anti-TNF to VDZ). In the VDZ to anti-TNF group, only proportion of 6 months treatment persistence was assessed due to the small number of pts in 2L. Median 1L treatment persistence was 842 days in VDZ pts and 557 days in anti-TNF pts (log rank p=0.041). The median treatment persistence in 2L VDZ post anti-TNF was 625 days (anti-TNF to VDZ). The 6 months treatment persistence to 2L was estimated as 85.1% (95% CI 59.1–95.2) in VDZ to anti-TNF group and 80.1% (95% CI 73.8–85.1) in anti-TNF to VDZ group. The 6 months treatment persistence was estimated as 74.8% (95% CI 73.4–76.1) in 1L anti-TNF and 85.1% (95% CI 59.1–95.2) in 2L anti-TNF post VDZ (VDZ to anti-TNF). Conclusion VDZ in 1L biologic treatment of CD was associated with significantly improved treatment persistence compared with anti-TNF agents. The sequencing of VDZ to anti-TNF had higher treatment persistence in both 1L and the first 6 months of 2L compared with the sequencing of anti-TNF to VDZ. The use of VDZ before anti-TNF agents led to higher persistence to anti-TNF in 2L than if anti-TNF was used in 1L during 6 months period of time. VDZ used in 2L post anti-TNF showed lower treatment persistence than if VDZ was used in 1L. This real-world evidence from U.S. large database suggests the use of GSALT prior to anti-TNF agents in biologic naïve pts with CD.

P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease

Abstract Background The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD). Methods A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed. Results We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1. In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05). Conclusion The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.

Real-World Evidence From More Than 1000 Patients Treated With Adalimumab For Moderate-to-Severe Psoriasis in the Czech Republic.

IntroductionThe study aimed to evaluate the real-world effectiveness of adalimumab as well as investigate the persistence of treatment and identify factors, which may affect it.MethodsMore than 1150 patients (4363.1 patient-years) with psoriasis who had been treated with adalimumab since the start of the BIOREP registry in the Czech Republic were included in this analysis. Treatment effectiveness was defined as improvement in Psoriasis Area and Severity Index (PASI). The analysis was performed during the years 2005 and 2018. Patients were on on-label dose.ResultsAfter 12 and 96 months of therapy, 84% and 88% of patients had a 75% reduction in PASI score from baseline, respectively. Drug survival was analyzed according to the number of previous biological therapies, and results showed 75% and 58.1% survival rate for biologically naïve patients in the 20th and 80th month of treatment, respectively. The negative predictors of adalimumab survival were the female gender, obesity, baseline PASI score and the number of previous biological therapies.ConclusionsBaseline factors including PASI, number of previous biological therapies, and sex were associated with shorter adalimumab survival. This long-term study shows that adalimumab is effective and has high treatment persistence.

Clinical Outcomes, Costs, and Healthcare Resource Utilization in Patients with Metastatic Merkel Cell Carcinoma Treated with Immune Checkpoint Inhibitors vs Chemotherapy.

PurposeMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer with poor prognosis. This study compared patient characteristics, comorbidities, adverse events (AEs), treatment persistence, healthcare resource utilization (HRU) and costs in patients with metastatic MCC (mMCC) treated with immune checkpoint inhibitors (ICIs) or recommended chemotherapy per 2018 National Comprehensive Cancer Network (NCCN) Guidelines.Patients and MethodsA retrospective, observational study was conducted using data from 3/1/2015 through 12/31/2017 from the Premier Healthcare Database, a US hospital discharge database. The study included patients aged ≥12 years with International Classification of Diseases Codes for MCC and metastasis, categorized by their first treatment (index) during the study period (ICI or NCCN-recommended chemotherapy [chemotherapy]). Patient, hospital, and visit characteristics were assessed at the index date and Charlson Comorbidity Index (CCI) score and comorbidities during a 6-month look-back period. Clinical outcomes, including AEs and treatment persistence were assessed over 90 days and HRU and costs over 180 days post-index.ResultsOf 75 patients with mMCC receiving ICIs (n=37) or chemotherapy (n=38), mean age was ≈73 years, and 21.3% had a history of immune-related (IR) conditions. Overall, ICI- and chemotherapy-treated patients were similar in most baseline characteristics, IR comorbidities, and CCI score. However, more ICI patients (46%) than chemotherapy patients (26%) persisted on treatment over 90-day follow-up, odds ratio (95% CI): 2.04 (0.93, 4.47), P=0.07. Over 180-day follow-up, 33% of patients had an inpatient admission with mean length of stay (LOS) ≈2 days shorter for ICI vs chemotherapy (not statistically significant). Total costs, primarily driven by pharmacy costs, were higher for ICIs than chemotherapy; other departmental costs were similar between treatment groups.ConclusionIn a real-world setting, patients with mMCC receiving ICIs had higher treatment persistence over 90 days, shorter inpatient LOS and similar departmental cost (excluding pharmacy cost) than those receiving chemotherapy.

SPOSAB ABP 501 - A SICILIAN PROSPECTIVE OBSERVATIONAL STUDY OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH ADALIMUMAB BIOSIMILAR ABP 501

Abstract Background and Aims There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. Methods SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive patients treated with ADA biosimilar ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled to assess its safety and effectiveness. Patients were divided into 3 groups: group A, naïve to ADA and naïve to anti-TNFs; group B, naïve to ADA, previously exposed to anti-TNFs; group C: switched from ADA originator to ABP 501. Results 559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six SAEs occurred in 36 patients [(6.4% - incidence rate (IR): 8.9 per 100 person-years (PY)]. The IR of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; IR ratio=3.61; p&amp;lt;0.001) and among patients in group B compared with group C (16.4 vs. 4.8 per 100 PY; IR ratio=3.42; p=0.041). Among ADA-naïve patients (group A+B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with group A and B (log-rank p&amp;lt;0.001). Conclusions Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

P361 The effect of immunomodulators and other factors on the persistence of biological agents for Crohn’s disease and ulcerative colitis: data from the Australian population-based registry

Abstract Background Treatment persistence (duration of medication use) provides real-world evidence on therapeutic effectiveness, tolerability and prescriber and patient preferences. Biological agent persistence in Crohn’s disease (CD) and ulcerative colitis (UC) was compared from a national population-based registry with no hierarchical prescribing order. We hypothesised immunotherapy co-therapy would increase persistence for anti-TNF agents, but not for non-anti-TNF agents due to reduced immunogenicity. Methods A randomly selected ten per cent subgroup of the prospectively collected population-based registry from the Australian Pharmaceutical Benefits Scheme between June 2005 and June 2019 was analysed. Treatment persistence of adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ) and ustekinumab (UST) was compared. Factors affecting discontinuation were evaluated using multivariate proportional hazard regression. Results 886 patients consisting of 1294 lines of therapy (992 CD, 302 UC, 2778 person-years of follow-up) were included. In CD, UST had the highest overall persistence rate (median persistence rate was &amp;gt; 74.6% where 24.6 months is the maximum follow-up time recorded), followed by VDZ, IFX and ADA (p = 0.03) (Figure 1). UST had the highest persistence as first, second and third-line therapies (p &amp;lt; 0.05). In UC, VDZ had the highest persistence rate (median persistence rate was &amp;gt;50.3% where 47.4 months is the maximum follow-up time recorded), followed by IFX and ADA (p &amp;lt; 0.001) (Figure 2). VDZ had the highest persistence rates as first-line therapy (p &amp;lt; 0.001), while second and third-line therapies did not demonstrate significant differences. Persistence of biological agents correlated with immunomodulator co-therapy in CD (R2: 0.65 p &amp;lt; 0.001) and UC (R2: 0.50 p &amp;lt; 0.001). Thiopurine co-therapy significantly increased persistence for IFX and ADA in CD and UC (p &amp;lt; 0.001) (Figures 3 and 4) but was not significant for UST and VDZ. Methotrexate decreased persistence for VDZ in UC and had no effects on UST, IFX and ADA in UC and CD. In acute-severe UC, there were no significant differences between IFX as monotherapy vs. co-therapy. On multivariate analysis, higher persistence was seen in males (HR: 0.75 95% CI: 0.59–0.94) and with immunomodulator co-therapy (HR 0.77 95% CI: 0.61–0.97, p = 0.03). Conclusion This real-world data reflecting treatment effectiveness, tolerability and patient and prescriber preferences supports the use of UST and VDZ over anti-TNF agents in CD and UC, respectively, to achieve high treatment persistence which is independent of immunomodulator co-therapy, possibly secondary to differing immunogenicity rates. It also highlights the substantial increase in anti-TNF therapy persistence with thiopurine co-therapy, but not with methotrexate.

728 Second-Line Biologic Therapy After Vedolizumab

INTRODUCTION: Vedolizumab (VDZ), an anti-integrin monoclonal antibody approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly being utilized as first-line biologic therapy in bio-naïve inflammatory bowel disease (IBD) patients (pts) with moderate-to-severe disease. While prior studies have described the efficacy of VDZ after anti-TNF failure, there is little guidance on the use of alternative biologics following initial VDZ therapy. This study describes the clinical response of IBD pts treated with a second (2nd) biologic following VDZ discontinuation. METHODS: We performed a retrospective review of all bio-naïve IBD pts started on VDZ as first-line therapy at a large multicenter gastroenterology private practice since drug approval in 2014. Pts were identified who failed initial VDZ treatment and were switched to a 2nd biologic agent. Data collection included demographics, diagnosis, therapy, and disease activity scores using the partial Mayo score (pMayo) for UC pts and the Harvey-Bradshaw Index (HBI) for CD pts. Clinical remission was assessed for those pts with ≥6 months of data and defined as pMayo less than 2 or HBI less than 5. RESULTS: A total of 135 IBD pts receiving VDZ as first-line biologic therapy were identified, of which VDZ was discontinued in 30 (22%). Our study cohort included 25 pts who received a 2nd line biologic following VDZ failure (11 primary non-response, 14 secondary non-response). Second-line biologic agents included 19 infliximab, 3 adalimumab, 2 ustekinumab, and 1 tofacitinib. Baseline demographics of the 25 pts were as follows: mean age 47 ± 18 years, male gender 13 (52%), UC 19 (76%), CD 6 (24%), time to 2nd biologic 8.2 ± 4.5 weeks. Disease severity scores prior to and following initiation of the 2nd line biologic are depicted in Figure 1. Clinical remission assessment was available for 18 of 25 patients. Remission was achieved in 11 of 18 pts (61%), driven by UC pts treated with infliximab [Figure 2]. Overall, pts treated with anti-TNF agents following VDZ had higher rates of remission compared to those treated with other biologics. CONCLUSION: Biologic-naïve IBD pts treated initially with VDZ have high treatment persistence. In addition, rates of remission with 2nd-line biologic therapy are significantly greater than expected when first-line failure is VDZ. Further studies are warranted to determine the optimal order in which advanced therapies should be initiated.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab – a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO)

Objectives: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn’s disease (CD) and ulcerative colitis (UC) patients.Methods: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation.Results: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=−5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =−0.5, p = .003) at month 6.Conclusions: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis Changing Biologics in the USA.

IntroductionAfter a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers.MethodsThis study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year. The index date was the date of the change in therapy. Treatment persistence was defined as no subsequent switch or 60-day gap in therapy for 1 year post-index. RA-related costs included plan-paid and patient-paid amounts for inpatient, outpatient, and pharmacy claims. Medication costs included index and post-index costs of TNFi and different MOA therapies.ResultsThere were 581 (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus 40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus $42,116; P < 0.001) and medication costs ($29,001 versus $34,917; P < 0.001). When costs were divided by treatment persistence, costs per persistent patient were lower among MOA switchers versus TNFi cyclers: $25,436 lower total RA-related cost and $25,999 lower medication costs.ConclusionMOA switching is associated with higher treatment persistence and lower healthcare costs than TNFi cycling. Reimbursement policies that require patients to cycle TNFi before switching MOA may result in suboptimal outcomes for both patients and payers.FundingSanofi and Regeneron Pharmaceuticals.

Persistencia en el tratamiento según el tipo de dispositivo inhalador en pacientes con asma y enfermedad pulmonar obstructiva crónica

ObjectiveTo assess the initial treatment persistence with inhaled corticosteroids and long-acting beta-2 adrenergic bronchodilators (ICS/LABA) depending on the inhaler device used (pMDI or DPI), for the treatment of asthma and COPD. Material and methodsAn multicenter observational study. Subjects in initial treatment with ICS/LABA during 2007-2011 were included, and a follow-up period of 3 years. 2 groups of study (asthma, COPD) and 2 subgroups were prepared according to the device type inhaler (pMDI or DPI). The main measurements were: sociodemographic, comorbidity, adherence (rate possession medication -RPM-), persistence, drugs, exacerbation rates, resources use, and their costs (direct and indirect costs). Multivariate methods were used for the variables correction, with significance level of P<.05. ResultsThe study included 2,082 asthma patients (pMDI: N = 566, 27.2%; DPI = 1,516, 72.8%). Patients with MDI devices showed a higher degree of persistence (32.5 vs. 27.8%; P=.037), treatment adherence (RPM: 83.1 vs. 80.5%; P<.001), fewer exacerbations (17.7 vs. 24.9%; P=.001) and lower health care costs (2,583 vs. 2,938 EUR; P = 0.042). 1,418 patients with COPD also were analyzed (pMDI: N = 524, 41.9%; DPI: N = 824, 58.1%) were analyzed. Patients with MDI devices also showed a higher degree of persistence (31.5 vs. 24.8%; P=.005), treatment adherence (RPM: 83.3 vs. 80.1%; P= .001), less exacerbations (40.1 vs. 48.2%; P=.002) and lower health care costs (3,922 vs. 4,588 EUR; P=.021). ConclusionspMDI devices (as ICS/LABA initial treatment) are associated with higher treatment persistence either in asthma or COPD, with lower exacerbation rates, and use of health resources and cost

Impact of Loss of Work Productivity in Patients with Overactive Bladder Treated with Antimuscarinics in Spain: Study in Routine Clinical Practice Conditions.

Overactive bladder (OAB) is a syndrome characterized by presenting symptoms of urgency, with or without urge incontinence, and normally accompanied by day and night frequency. The aim of this study was to evaluate the impact of lost work productivity [number of days of sick leave] in patients treated with fesoterodine versus tolterodine and solifenacin to treat OAB in Spain. A retrospective, observational study was carried out using the records (digital databases) of actively working patients (2008-2013). The study population comprised of patients from two autonomous communities; 31 primary care centres agreed to participate. Patients who began first treatment with antimuscarinics (fesoterodine, solifenacin or tolterodine) and who met certain inclusion/exclusion criteria were included in the study. Follow-up lasted for 1year. The main outcome measures were comorbidity, medication possession ratio (MPR), treatment persistence, and number of days of sick leave and associated costs. Indirect costs were considered to be those related to lost work productivity (number of days of sick leave, exclusively), (1) due to OAB and (2) overall total. The cost was expressed as the average cost per patient (cost/unit). Multivariate analyses (Cox, ANCOVA) were used to correct the models. A total of 3094 patients were recruited into the study; 43.0% were treated with solifenacin, 29.2% with tolterodine, and 27.8% with fesoterodine. The average age of patients was 54 years (standard deviation 9.2), and 62.2% were women. The comparison of fesoterodine versus solifenacin and tolterodine showed a higher MPR (90.0 vs. 87.0 and 86.1%, respectively), higher treatment persistence (40.2 vs. 34.7 and 33.6%), lower use of sick leave (22.8 vs. 52.9 and 36.7%), total number of days of sick leave (5.1 vs. 9.7 and 9.3days) and costs corrected for covariates (€371 vs. €703 and €683); p<0.05. Despite the possible limitations of this study, active patients who began treatment with fesoterodine to treat OAB (compared with solifenacin or tolterodine) had fewer days of sick leave, resulting in lower costs due to lost productivity.

Abstract 18371: Higher Treatment Persistence of Non-Vitamin K Antagonist Oral Anticoagulants than Vitamin K Antagonists at 1 Year in Non-Valvular Atrial Fibrillation in Real-World Practice

Introduction: Oral anticoagulants (OAC) are under-utilised in atrial fibrillation (AF). Even patients prescribed an OAC may stop taking the drug soon after treatment initiation, particularly with Vitamin K Antagonists (VKA). The Non-VKA OAC (NOAC) drugs offer greater ease of use, and persistence is likely to be higher. Aim: To determine persistence on treatment in the first year after inception of NOACs and VKA in incident AF in real-world clinical practice. Methods: We studied 24,467 OAC-naïve patients with incident non-valvular AF diagnosed between Jan 2011-Feb 2014, mean age 73.9 ± 12.5, 45.6% female, in a very large UK primary care database (Clinical Practice Research Datalink, CRPD), with full linkage to medication use. Follow up was for a mean of 1.2 ± 0.9 years. The proportion of OAC initiation in the 90 days after first-time AF and of those remaining on OAC one year after initiation were estimated using competing risk survival analyses censoring for use of alternative OAC. Results: NOAC drugs prescribed included Rivaroxaban, Dabigatran and Apixaban. Overall, 12,579 (51.4%) were commenced on an OAC: 11,888 on VKA and 691 on NOAC, within 90 days after incident AF. Amongst all OAC users, the proportion taking NOAC increased from 0.3% in 2011 to 12.3% in 2014. Persistence, defined as the proportion still taking the OAC after one year, declined over the 12 months to 54.3% for VKA and 80.7% for NOAC (Table). Persistence was significantly greater for NOAC than VKA at all time points. Conclusions: There is a progressive fall in VKA use amongst OAC naïve patients with AF in real-world practice to only 54% at 1 year. This contributes to under-utilisation of anticoagulation in AF and would result in an increased rate of stroke. Persistence was significantly improved with NOACs compared to VKA, and this factor alone could lead to reduced stroke burden with increasing uptake of the NOACs.

Outcomes and treatment patterns of adding a third agent to 2 OADs in patients with type 2 diabetes.

Patients with uncontrolled type 2 diabetes mellitus (T2DM), despite therapy with 2 oral antidiabetic drugs (OADs), may add a third OAD or a glucagon-like peptide-1 receptor agonist (GLP-1) or initiate insulin therapy. The transition to insulin has been shown to be delayed in current practice, potentially through clinical inertia--the failure of health care providers to initiate or advance therapy when indicated. Patients and physicians may be resistant to insulin therapy because of beliefs about side effects and limitations to patients' lifestyle, while patients may consider that starting injectable therapy signifies a considerable worsening of their disease and may feel they have "failed" to manage it effectively. To describe current treatment patterns and outcomes among adult patients with T2DM in the United States who were treated with 2 OADs and added a third antidiabetic drug. This retrospective study followed patients with T2DM who added a third OAD (the "3OAD" cohort), insulin ("+Insulin"), or a GLP-1 ("+GLP-1") between July 2000 and March 2009. Patients were followed for up to 2 years. Baseline characteristics and follow-up outcomes--including blood glucose level (HbA1c), hypoglycemia, and health care costs--were examined. Treatment persistence was assessed to determine how long patients continued with their prescribed medications without discontinuing or switching. A total of 51,771 patients adding a third agent to their 2OAD regimen were included in this study. Most patients added a third OAD (n = 41,052) over insulin (n = 6,904) or GLP-1 (n = 3,815). At baseline, +Insulin patients were older, with higher comorbidity burden and higher HbA1c. During follow-up, 3OAD patients were more likely to be persistent with their treatment than +Insulin or +GLP-1 patients, but +Insulin patients had the greatest HbA1c reduction from baseline, while continuing with insulin treatment was associated with higher HbA1c reduction. Among 3OAD patients, most of those who switched a third agent initiated insulin, and those who switched early during the follow-up period had greater HbA1c reduction than those who continued with the 3OAD treatment regimen. Average annual health care costs declined in +Insulin patients but increased among 3OAD and +GLP-1 patients. Treatment persistence and HbA1c reduction in +GLP-1 patients were low. This study found that in current practice, physicians seem to be reluctant to prescribe injectable agents for patients with uncontrolled T2DM despite combination OAD therapy. Despite higher treatment persistence among patients adding a third OAD, this persistence did not translate into better glycemic control and may not necessarily be a long-term cost-saving solution. These data indicate a need for more evidence-based and patient-centered treatment decisions for patients unable to achieve and maintain glycemic targets on multiple OADs.

Comparison of treatment persistence, hospital utilization and costs among major depressive disorder geriatric patients treated with escitalopram versus other SSRI/SNRI antidepressants

ABSTRACTObjective: To assess treatment persistence, hospitalization outcomes and mean healthcare costs of geriatric major depressive disorder (MDD) patients treated with escitalopram compared to other selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs).Research design and methods: Patients aged ≥ 65 years with at least one inpatient claim or two independent claims associated with MDD diagnosis were identified in the IHCIS National Managed Care Database (2003–2005). Patients were continuously enrolled for at least ≥ 12 months, filled at least one prescription for an SSRI/SNRI and did not use any second-generation antidepressant during the 6 months pre-index date. Unadjusted and multivariate analyses adjusting for baseline characteristics were conducted.Main outcome measures: Treatment persistence, hospitalization utilization, and average prescription drug, medical, and total healthcare costs were compared between patients initiated on escitalopram versus other SSRI/SNRIs.Results: Escitalopram-treated patients (N = 459) were less likely to discontinue treatment (HR = 0.85, p = 0.012) or switch to another second-generation antidepressant (HR = 0.76, p = 0.006) compared to patients treated with other SSRI/SNRIs (N = 1517). Escitalopram-treated patients had 39% fewer hospitalization days ( p = 0.004). Both groups had similar mean prescription drug costs ($1659 vs. $1630, p = 0.687). After controlling for baseline characteristics, escitalopram-treated patients had lower mean total medical service costs ($9425 vs. $12 703, p < 0.001) and mean total healthcare costs ($11 043 vs. $14 163, p < 0.001).Limitations: This study's limitations include its small sample size, short observational periods and exclusivity of indirect costs.Conclusions: Geriatric patients treated with escitalopram had higher treatment persistence, fewer hospitalization days and lower total healthcare costs than patients on other SSRI/SNRIs after controlling for baseline characteristics. Most of the cost savings were due to reductions in hospitalizations.

Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year, open-label extension study

ABSTRACTObjectives: This analysis evaluated the long-term safety, tolerability and efficacy of darifenacin, a muscarinic M3 selective receptor antagonist, in the treatment of overactive bladder (OAB) in patients ≥ 65 years of age.Methods: Patients who completed one of two 12-week, placebo-controlled, double-blind, feeder studies received once-daily (o.d.) treatment with darifenacin 7.5 mg for the first 2 weeks of the 2-year, open-label extension study. The dose could be subsequently adjusted (7.5 or 15 mg o.d.) according to need. Safety and tolerability were assessed, and efficacy variables/endpoints were evaluated from patient diary data.Results: 214 patients (65–89 years) entered and 137 (64.0%) completed the 2-year extension study, amounting to 308 patient-years’ drug exposure. Darifenacin was well tolerated with no new safety concerns. The most common adverse events (AEs) were dry mouth and constipation, which infrequently resulted in discontinuation (2.3% and 4.2%, respectively). Darifenacin produced significant improvements in OAB symptoms that were maintained over the 2-year period (median reduction from feeder-study baseline to 2 years: –11.0 [–83.7%] for incontinence episodes/week and –1.2 [–12.4%] for micturitions/day, both p < 0.05), with 44.4% patients achieving ≥ 90% reduction in incontinence episodes at 2 years.Conclusions: Darifenacin demonstrated good tolerability and safety in older patients with OAB. The improvement in OAB symptoms was sustained throughout the 2-year extension, resulting in high treatment persistence rates. Results were comparable with those in the overall OAB population from this study, indicating that darifenacin treatment is effective and well tolerated irrespective of age.

Once-monthly ibandronic acid along with patient support is associated with higher treatment persistence than once-weekly alendronic acid

Once-monthly ibandronic acid along with patient support is associated with higher treatment persistence than once-weekly alendronic acid