Rate Of Therapy Discontinuation Research Articles

Pharmacoeconomic analysis of using biological agents in the treatment of rheumatoid arthritis

By taking into account the fact that there are a few alternative biological agents for the treatment of rheumatoid arthritis (RA), the cost of an annual therapy cycle using the agents is greater than that of high-technology surgical interventions, and a pharmacoeconomic study substantiating the optimal choice of a specific drug has been conducted. The pharmacoeconomic analysis has indicated the use of the biological agents etanercept (ETC) can decrease the cost of an annual therapy cycle for each patient with RA by an average of 84,764–481,622 rubles and considerably increase the number of patients receiving the current therapy without allocating additional resources. Switching 100 patents with RA to a treatment regimen including ETC enables 14–78% of the patient with this condition to be additionally treated within the framework of the same budget. The given results with regard to the data that there are significant differences in the efficacy and safety of biological agents used to treat RA (National and EULAR guidelines for the treatment of RA, a number of meta-analyses of randomized controlled clinical trials) may conclude that the treatment regimen incorporating ETC is most preferential. The cost-effectiveness analysis based on the single meta-analysis proposed by G.J. Bergman et al., which had demonstrated differences in the efficacy of biological agents, also yielded the similar results. In this case, the administration of ETC is also more preferential because it can minimize expenditures of the health care system to achieve ACR20 and ACR50 responses. This advantage of ETC will cause the highest reduction in the number of hospital admissions, social benefits, and other expenses associated with the management of patients with RA. The authors are aware of the disadvantages of the performed trial, which cannot fully interpret uniquely the findings: the results of meta-analyses have limitations due to its low sensitivity in assessing the differences between the drugs; the virtually complete absence of published data on the direct comparison of the drugs, by employing sufficient patient samples, makes it necessary to use the data of the meta-analyses and to state that biological agents have similar efficacy and safety within the clinically permissible limit to recognize their equivalence; the trial has considered only an annual perspective to use the agents without regard for their therapy discontinuation rate and remission rate that requires that treatment should not be continued.

Abstract 18404: Warfarin Persistence in Atrial Fibrillation: The Michigan Anticoagulation Quality Improvement Initiative Experience

Introduction: Warfarin reduces the risk of stroke in patients with atrial fibrillation (AF), but increases the risk of bleeding. In clinical trials, persistence with warfarin therapy ranges from 75-79% at one year, but few studies offer real-world estimates of warfarin persistence. There is limited data demonstrating the relationship between CHADS2 and HAS-BLED scores with adherence to warfarin. Methods: New patients treated with warfarin for stroke prevention in AF were followed at seven anticoagulation clinics involved in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) collaborative. Patients were excluded if they had additional indications for warfarin such as artificial valve, DVT, or PE. Risk factors for CHADS2 and HAS-BLED scores and reasons for warfarin discontinuation were abstracted from patient charts. Kaplan-Meier (KM) curves were constructed to characterize drug therapy discontinuation rates at one year. Cox proportional hazard regression and logistic regression analyses were performed to assess the effects on warfarin persistence by CHADS2 and HAS-BLED scores. Results: Of 1,973 eligible patients, 153 (7.8%) switched to non-warfarin therapy (e.g. dabigatran). In the remaining 1820 patients, one year persistence is 63% based on KM estimates. One year persistence by low, intermediate, or high CHADS2 score was 29%, 58%, and 73%, respectively. One year persistence for low, intermediate, or high HAS-BLED score was 41%, 66% and 76%, respectively. Warfarin persistence at one year was associated with an increasing CHADS2 (OR 1.244, CI 1.045-1.482) but not associated with HAS-BLED score (OR 1.016, CI 0.839-1.231) in multivariate analysis. Conclusions: A significant proportion of patients taking warfarin for SPAF discontinue therapy by one year. In the multivariate analysis, patients at higher risk of stroke, but not bleeding, are more likely to remain on warfarin therapy. Efforts to improve warfarin persistence need further investigation.

Bendamustine, Bortezomib and Dexamethasone (BVD): A Combination With a Substantial Activity and a Manageable Toxicity In Patients With Relapsed-Refractory Multiple Myeloma (MM)

Bendamustine, a bi-functional alkylating agent comprising a purine-like benzimidazole ring an a nitrogen mustard group, exerts a peculiar mechanism of action if compared to most conventional alkylators and this may partially explain its effectiveness in alkylator-resistant cells. In patients with MM several studies demonstrated the efficacy and tolerability of bendamustine as monotherapy or in combination with new drugs, particularly bortezomib that was found to enhance the in vitro sensitivity of MM cells to bendamustine.These observations represented the rationale for our protocol design namely to evaluate the combination bendamustine (70 mg/m2 days 1, 8), bortezomib (1.3 mg/ m2 days 1, 4, 8, 11) and dexamethasone (20 mg days 1-2, 4-5, 8-9, 11-12) (BVD). Cycles were administered every 4 weeks up to four cycles. Patients achieving a response less than a PR were taken off-study. Patients obtaining at least a PR received two additional treatment cycles followed by a 12-months consolidation phase with cycles repeated every 2 months. Therefore, patients with a PR after the induction phase could receive up to 18 months of treatment and up to 12 cycles of BVD. Patients with relapsed/refractory MM of any age, with adequate cardiac, liver and hematological function, not refractory to bortezomib and treated with no more than four previous lines of therapy were enrolled in this prospective, single-arm, open-label, phase II study conducted in 21 Italian centres. The primary endpoint was achievement of a response at least PR after four cycles of BVD and response was assessed according to to IMWG criteria.From March 2011 to June 2012, 75 patients were included. Median age was 68 years (range 41-85), 26.5% had ISS stage 3, 19% IgA myeloma and 9% renal failure. In total, 8 of 36 evaluable patients (22%) had adverse cytogenetics. All patients had received prior treatment with new drugs, including targeted agents such as thalidomide (57%), lenalidomide (54.5%) or bortezomib (46.5%). Patients had received a median of one prior line of therapy (range 1-4), including alkylators (69%), anthracyclines (29%) and ASCT (44%). Twenty-four patients (32%) were refractory to IMIDs.The response rate ≥ PR after four cycles of BVD was 71.5%, including 11 patients with CR (16%), 13 VGPRs (18.5%) and 26 PRs (37%). Also, 14 patients (20%) had disease stabilization while 6 (8.5%) had progressive disease. Median time to response was 1.2 months (range 0.9-1.4 months). Only prior treatment with bortezomib significantly reduced the response rate ≥ PR (54.5% vs 86.5%; P = 0.003).At a median follow-up of 12 months (range 6-24), 30 patients had progressed and 18 had died. Median TTP and PFS were 16.5 months and 15.5 months, respectively while median OS had not been reached and 78% of patients were alive at 1 year. The Cox regression analysis identified prior therapy with bortezomib plus lenalidomide as the only factor that significantly reduced TTP (9 vs 17 months; HR = 4.5; 95% CI = 1.7-12.3; P = 0.005)Grade 3-4 adverse events occurred in 55% of patients leading to therapy reduction in 20% and to protocol discontinuation in 10.5% of patients. The most frequent severe adverse events were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), peripheral neuropathy (8%), gastrointestinal and cardiovascular events (both 6.5%). Compared with younger, patients aged > 70 years had a significantly higher incidence of grade 3-4 thrombocytopenia (22% vs 37%; p=0.042) and severe infections (7 vs 19%; p=0.047) and consequently a higher rate of therapy reduction (9% vs 34.5%; p=0.007) and therapy discontinuation (7% vs 15.5%; p=0.043). Moreover, 4/5 early deaths occurred in patients aged more than 70 years.BVD combination is an effective regimen in relapsed-refractory MM patients since it elicits rapid, high (> 70%) and good quality of response (more than a third of patients achieved CR + VGPR). Moreover, BVD combination is a feasible and well tolerated regimen provided that adapted therapy and adequate antibiotic prophylaxis are employed in patients older than 70 years. Disclosures:Offidani:Mundipharma: Honoraria, Research Funding. Off Label Use: Bendamustine.

Treatment of Chronic Myeloid Leukemia Elderly Patients in the Tyrosine Kinase Inhibitor Era

The prevalence of chronic myeloid leukemia (CML) is expected to double in the next 15 years. The introduction of imatinib significantly changed the prognosis of CML, challenging the concept of a fatal disease. Nowdays, imatinib, nilotinib and dasatinib are registered for first-line treatment of CML patients in chronic phase (CP). Considering elderly patients, the most extensively studied TKI is imatinib, that induces a rate of cytogenetic and molecular responses comparable between the younger and the elderly patients. Once a CCgR with imatinib is achieved, the probability to be alive and disease free at 8 years is more than 80%. These results confirm that imatinib has to be considered the first-line treatment for the elderly and that the CCgR is the guide parameter for treatment modulation and the most solid marker of long term outcome. Nevertheless, older patients tolerate imatinib worse in comparison to the younger, and this causes a higher rate of therapy discontinuation and less adherence to chronic treatment. Thus, the toxic profile of each TKI is one of the most important factors driving the choice of the best drug. Another important factor is the potency of the TKI. Since nilotinib and dasatinib are more potent than imatinib in inducing cytogenetic and molecular responses, they could be preferred for increasing the proportion of patients who can achieve deeper molecular responses, allowing treatment discontinuation. This approach is intriguing, but it is still experimental. Another therapeutic strategy could be the identification of the minimal effective dose of TKI in order to maintain the CCgR, but also this approach is under clinical investigation.

Treatment Patterns and Health Care Costs for Patients With Psoriatic Arthritis on Biologic Therapy: A Retrospective Cohort Study

BackgroundBiologic therapies have been used in patients with psoriatic arthritis (PsA) who have been inadequately treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). ObjectiveExamine treatment patterns and health care costs among patients with PsAs who initiated biologic therapy either as monotherapy or adjunctively with traditional DMARDs. MethodsThe MarketScan® database was used to identify adults with PsA who initiated therapy with a biologic (with first use identified as index date). Patients were required to have a 6-month pre-period with no biologic use and 1 year insurance eligibility pre- and post-index date. Cohorts of patients initiating biologic therapy either as monotherapy or adjunctively with traditional DMARDs were created. Medication use patterns including discontinuation, switching, and restarting were identified during the 1-year follow-up period. Cox proportional hazards models were conducted to compare time to discontinuation of index biologic, and logistic models were used to compare the rate of discontinuation and biologic switching between the 2 cohorts. All-cause and PsA-related costs were compared between the 2 cohorts using propensity score-adjusted bootstrapping methods. All comparisons were made after adjusting for age, sex, Charlson comorbidity index, and PsA-related total cost over 1-year pre-index date. ResultsAmong the 3164 PsA patients identified, 67.7% initiated biologics as monotherapy and 32.3% initiated biologics adjunctively with traditional DMARDs. The number of patients on pain medications, topical medications, and traditional DMARDs was significantly lower post index date compared to pre-index date (P < 0.01), while use of antihypertensives, antidiabetics, and statins increased after patients initiated biologic therapy. In 1-year post-period, approximately half of the patients (50.9%) who initiated a biologic continued their index biologic with an average time to discontinuation of 279.8 days for all patients. Rates of discontinuation, switching, and restart were 33.1%, 9.9%, and 6.1%, respectively, for all patients. Rates of switching and restart were similar between the 2 cohorts, but a significantly lower rate of discontinuation was observed in the biologic plus traditional DMARDs cohort than the biologic monotherapy cohort. Pharmacy expenditures were higher for the biologic + DMARD cohort than the biologic-monotherapy cohort ($14,486 vs $14,062; P = 0.0348). No statistically significant differences for either all-cause or PsA-specific costs were observed across the treatment cohorts. ConclusionsTraditional DMARDs used in combination with biologic therapy appear to reduce rates of biologic therapy discontinuation.

Methadone maintenance therapy decreases the rate of antiretroviral therapy discontinuation among HIV-positive illicit drug users.

We sought to examine whether methadone maintenance therapy (MMT) decreased rates of antiretroviral therapy (ART) discontinuation and was associated with plasma HIV RNA responses among a cohort of illicit drug users. Cumulative ART discontinuation rates were estimated using Kaplan-Meier methods and factors independently associated with ART discontinuation were identified using Cox proportional hazards regression. Engagement in MMT was negatively and independently associated with ART discontinuation [Adjusted Relative Hazard=0.67 (95% CI 0.54-0.83); p<0.001]. Among participants receiving ART and MMT, 81.6% of plasma HIV-1 RNA assessments were <500 copies/mL, while 65.81% of HIV-1 RNA assessments among those prescribed ART without MMT were <500 copies/mL (p<0.001). These results demonstrate that engagement in MMT conferred a protective benefit against ART discontinuation and was associated with a significant increase in plasma HIV RNA suppression among HIV-infected opioid-dependent drug users.

EFFICACY AND SAFETY OF FIXED RAMIPRIL + FELODIPINE COMBINATION IN TREATMENT OF ARTERIAL HYPERTENSION: A RETROSPECTIVE STUDY-FORECAST

Approximately 30-50% of the world's adult population suffer from arterial hypertension, and only 30-35% is successfully treated. A large number of patients with arterial hypertension require a combination of antihypertensive medications to achieve target blood pressure. The ESH/ESC recommendations suggest the use of fixed dose combinations for treatment simplification and improved adherence to treatment. The aim of this study was to evaluate efficacy and safety of fixed ramipril + felodipine combination in therapy of essential arterial hypertension. This multicentric, cross-sectional, non-interventional study evaluated 1.341 adult patients with essential arterial hypertension, defined by systolic and diastolic blood pressure increase (BP≥140/90 mmHg), only systolic blood pressure increase or antihypertensive therapy usage. All patients were treated with fixed-dose combination therapy ramipril + felodipine (5+5mg and 2.5+2.5mg) (Triapin® and Triapin mite®) therapy for at least two months. Efficacy was evaluated by proportion of patients who achieved target blood pressure values (<140/90 mmHg and <130/80 mmHg in diabetics) or defined blood pressure reduction (≥15/10mmHg). Safety of ramipril + felodipine therapy was evaluated based on the incidence of adverse events (AE) and therapy discontinuation rate during observational period. Therapy prescription was based on physician decision according to everyday clinical practice and 15 consecutive eligible patients were enrolled by each physician from the cohort of hypertensive patients treated in ambulatory setting. Patient population consisted of 647 (48.4%) males and 690 (51.7%) females (mean age 60.15±11.84 and mean duration of hypertension 9.5±7.34 years). Males were significantly younger (58.74±15.5 vs. 61.45±11.04, p<0.01) without difference in body mass index. There were 47.5% of patients with stage II, 29.2% with stage I and 23.3% with stage III. There was a significant reduction of systolic/diastolic BP and heart rate in patients with ramipril + felodipine combination (162.6±17/97.2±9 mmHg and 79.4±12/min) compared to baseline values prior to treatment (136.9±17/84.2±9 mmHg and 73.2±10 /min, p<0.01). Group with Triapin mite had lower reduction of systolic/diastolic BP compared to Triapin 21.4±15.9/11.6±9.8 vs. 28.9±19.2/14.1±11.0 mmHg and lower reduction of heart rate 6.1 vs. 6.3 /min (p<0.01). In total, 39.3% of patients reached target BP with or without target BP reduction, 30.0% reached only BP reduction and 30.7% did not reach target values. More patients reached target BP (48.4 vs 32.%) and less achieved defined BP reduction (18.8 vs. 38.9%) on Triapin mite therapy compared to Triapin (p<0.01). The proportion of patients who failed to reach any of these endpoints is similar in both treatment modalities. AEs were present in 34 patients (2.5%): headache in 9 (0.7%), lower leg swelling in 8 (0.6%) and dry cough in 4 (0.2%) cases - these were reported as the most frequent. None of reported adverse events was serious. Therapy continuation was reported in 92.6% of patients. Reasons for therapy discontinuation were insufficient drug efficacy in 29 (2.2%) patients; AE in 28 (2.1%) patients and other reasons in 34 (2.6%) patients. Triapin therapy efficacy and safety evaluated by physicians were: excellent efficacy in 824 (61.4%) patients and excellent safety in 870 (64.9%) patients. Fixed dose combination of ramipril + felodipine was shown to be an effective antihypertensive therapy in patients with essential arterial hypertension and an alternative approach to monotherapy for the initial management of essential hypertension. Small proportion of patients discontinued from ramipril+felodipine therapy and rare AEs indicate excellent safety profile.

Outcomes of sunitinib therapy in patients (pts) with metastatic renal cell carcinoma (mRCC) with poor risk features.

476 Background: Temsirolimus is perceived as the standard of care in pts with mRCC with poor risk features. However, sunitinib (Su) is commonly used in this setting. In this study, we assessed the use of Su in an unselected mRCC population. Methods: Retrospective analysis of 51 pts with mRCC and ≥ 3 poor prognosis features, as determined in the Advanced Renal Cell Carcinoma (ARCC) trial, treated with Su between January 2006 and July 2012. Primary outcome was overall survival (OS). Clinical and laboratory parameters were evaluated, as well as Su-related adverse events (AE). Median time to treatment failure (mTTF) and OS were estimated by Kaplan–Meier methods. On exploratory grounds, univariate, and multivariate analysis using Cox regression model was performed to determine possible prognostic variables. Results: Median age was 60 years (26-89). Most had clear cell histology (98%), 19% prior systemic treatment, and 51% prior nephrectomy. 64%, 15%, and 4% had 4, 5, and 6 adverse prognosis factors respectively. 88% had diagnosis to treatment intervals &lt; 1 year and 45% had KPS scores of &lt; 80. A median of 2 cycles (0–12) were administered. 63% received standard regimen of Su (50 mg/d 4 wk on/2 wk off). Reasons for discontinuation were disease progression (63%) and adverse events (21%). Most grade ≥ 3 AE were fatigue (14%), neutropenia (8%), and stomatitis (8%). 17%, 25%, and 14% developed hypothyroidism, hand-foot syndrome (HFS), and hypertension, respectively. Two therapy-related deaths were observed (one febrile neutropenia and one intracranial hemorrhage). Estimated mTTF and mOS of this cohort were 2.4 and 6.6 months, respectively. Multivariate analysis revealed that in a model adjusted for type of Su regimen, KPS, presence of brain metastasis, and occurrence of HFS, only Su-associated hypothyroidism was significantly associated with survival (respectively, odds ratio [OR] = 0.23; 95% CI = 0.07-0.68). Conclusions: Pts with mRCC with poor risk features treated with Su have an OS, TTF and rates of therapy discontinuation due to AE comparable to clinical trial subsets of similar pts. Our data suggest that the development of hypothyroidism in this setting might be useful as a predictor of OS, and this finding should be further investigated.

Weekly intravesical bacillus Calmette-Guerin (BCG) alternating with epirubicin in Ta and T1 urothelial bladder cancer: An approach to decrease BCG toxicity

Context:Bacillus Calmette-Guerin (BCG) therapy is the standard treatment for nonmuscle-invasive bladder cancer (NMIBC). However, its toxicity is a major concern.Aim:If we reduce the number of BCG doses by half and replace the second half with epirubicin, we may have a lower toxicity while maintaining the same efficacy of BCG. To test this hypothesis, we conducted this study as an update of our previous report.Setting and Design:The study included 607 patients with Ta and T1 NMIBC between January 1994 and December 2008.Materials and Methods:After transurethral resection of bladder tumor (TURBT), the patients received weekly doses of 120 mg BCG alternating with 50 mg epirubicin for six weeks (three weekly doses of each). Maintenance was given. Recurrence, progression rates, and toxicity were assessed. End points were progression, recurrence, and cancer-specific survival.Results:A total of 532 patients were eligible for evaluation (mean age: 58 years; median follow-up: 45 months). Of these, 291 (55%) were free, 157 (29.5%) showed recurrence, and 84 (15.8%) showed muscle-invasive progression. Toxicity developed in 221 patients. These were mild in the majority (167), whereas 10 developed hematuria, 30 severe cystitis, and five systemic complications. The rate of permanent therapy discontinuation was 3.8%.Statistical Analysis Used:SPSS package version 16 and Kaplan-Meier curves were used to evaluate survival.Conclusions:Reducing the frequency of BCG instillations by half and replacing the second half with epirubicin results in a similar efficacy and a lower toxicity compared with historical cases receiving BCG alone. However, further trials are required to support these results.

Comparison of the efficacy of ribavirin plus peginterferon alfa‐2b for chronic hepatitis C infection in patients with and without coagulation disorders

Many patients with coagulation disorders are infected with hepatitis C virus (HCV) that advances to end stage liver disease, resulting in an increased number of deaths. The efficacy of ribavirin and peginterferon combination therapy for chronic HCV infection in patients with coagulation disorders has not been clarified fully. The aim of this study was to evaluate the efficacy and tolerability of combination therapy in this patient population compared with patients who are infected with HCV and do not have coagulation disorders. A total of 226 consecutive chronic hepatitis C patients were treated with combination therapy and divided into two groups: patients with (n = 23) and without coagulation disorders (n = 203). Clinical characteristics, sustained virological response rates obtained by an intention-to-treat analysis, and combination therapy discontinuation rates were compared between the two groups. The sustained virological response rates did not differ significantly between patients with and without coagulation disorders (65.2% vs. 47.8% by intention-to-treat analysis). According to a multivariate analysis, age, alanine aminotransferase, gamma-glutamyltransferase, and HCV genotype were associated significantly with a sustained virological response, whereas whether a patient had a coagulation disorder did not affect the sustained virological response. In conclusion, combination therapy for chronic hepatitis C was comparably effective between patients with and without coagulation disorders and did not result in adverse bleeding.

Double Antiplatelet Therapy After Drug-Eluting Stent Implantation: Risk Associated With Discontinuation Within the First Year

The goal of this study was to assess the risk associated with double antiplatelet therapy (DAT) discontinuation, and specifically, temporary discontinuation, during the first year after drug-eluting stent (DES) implantation. Doubts remain about the risk of temporary DAT discontinuation within 1 year after DES implantation. A total of 1,622 consecutive patients undergoing DES implantation at 29 hospitals were followed up at 3, 6, 9, and 12 months to record the 1-year antiplatelet therapy discontinuation (ATD) rate, the number of days without DAT, and the rate of 1-year major cardiac events. Cox regression was used to analyze the association between ATD considered as a time-dependent covariate and 1-year cardiac events. One hundred seventy-two (10.6%) patients interrupted at least 1 antiplatelet drug during the first year after DES implantation, although only 1 during the first month. Most (n=111, 64.5%) interrupted DAT temporarily (median: 7 days; range: 5 to 8.5): 79 clopidogrel (31 temporarily), 38 aspirin (27 temporarily), and 55 both drugs (53 temporarily). Discontinuation was followed by acute coronary syndrome in 7 (4.1%; 95% confidence interval [CI]: 1.7 to 8.2), a similar rate of major cardiac events to that in patients without ATD (n=80; 5.5%; 95% CI: 4.4 to 6.8; p=0.23). ATD was not independently associated with 1-year major cardiac events (hazard ratio: 1.32 [95% CI: 0.56 to 3.12]). ATD within the first year and beyond the first month after DES is not exceptional, is usually temporary, and does not appear to have a large impact on risk.

Etanercept and Adalimumab Treatment Patterns in Psoriatic Arthritis Patients Enrolled in a Commercial Health Plan

Treatment patterns, including persistence, gaps in therapy, switching, and discontinuation, were examined in patients with psoriatic arthritis (PsA) who received the tumor necrosis factor (TNF)-blockers etanercept or adalimumab. This retrospective study utilized administrative claims data from a United States commercial health plan. Adults (age 18-64 years) with PsA who started therapy with etanercept or adalimumab as index therapy between January 1, 2006 and December 31, 2008 were included in the analysis. Patients were continuously enrolled in the health plan for at least 6 months before and at least 12 months after the start of index therapy. Initial TNF-blocker dose and rates of therapy persistence (continuous use of index medication without a gap of at least 60 days), therapy gaps, and discontinuation (gap in therapy of at least 60 days) were estimated. Those who discontinued were further classified as: (1) discontinued all biologic therapy, (2) restarted index medication, (3) switched to another biologic therapy, or (4) other. A total of 346 patients with PsA (202 etanercept, 144 adalimumab) were eligible. Most (90.6% etanercept; 88.9% adalimumab) started index therapy at the labeled dose. Persistence with index therapy for 12 months was observed in 50% of patients on etanercept and 45% of patients on adalimumab (P = 0.37). Patients on etanercept had a longer duration of persistence (434 vs. 353 days; P = 0.02), more pauses of at least 7 days (4.7 vs. 3.5; P = 0.004), and a longer mean pause length (48.6 vs. 29.3 days; P = 0.01) than patients on adalimumab. Of patients who discontinued (24.8% etanercept; 35.1% adalimumab), 46.4% and 41.5% restarted etanercept and adalimumab, respectively; 24.8% and 35.1% discontinued all TNF-blockers; 20.0% and 19.2% switched to another biologic; and 8.8% and 4.3% had other therapy changes. Approximately half of PsA patients were persistent on their index TNF-blocker for 12 months. Pauses in therapy and therapy discontinuation were common, but more than 40% of patients restarted their index TNF-blocker after discontinuation.

Length of adjuvant imatinib therapy in GIST: Weighing benefits, side effects and costs

A recent large randomized clinical trial showed a survival advantage with 36 vs 12 months of adjuvant imatinib in patients with resected gastrointestinal stromal tumors (GISTs). However, there was a higher therapy discontinuation rate with the longer duration of treatment. Preferences of individual GIST patients and the imatinib risk/benefit ratio should always be sought before employing this agent in adjuvant setting for longer than 12 months. A shorter duration of therapy may be preferred in patients with a limited life expectancy, serious cardiovascular co-morbidities, diminished compliance or poor adherence to oral therapy. Further study of underlying economic, psychosocial, and physical barriers of longer vs shorter duration of adjuvant therapy in this patient population is probably warranted.

S-1 monotherapy for previously treated non-small cell lung cancer: A retrospective analysis by age and histopathological type

S-1, an oral fluoropyrimidine derivative, has been approved for the treatment of non-small cell lung cancer (NSCLC) in Japan. In the present study, the efficacy and safety of S-1 monotherapy for elderly patients with previously treated NSCLC were retrospectively evaluated, and the efficacy of S-1 monotherapy was compared by histopathological type. This retrospective study included 54 patients with advanced or recurrent NSCLC who had received S-1 monotherapy following the failure of previous chemotherapy regimens at our institutes. Patient outcomes were compared based on their age and histopathological type. S-1 was administered orally, twice daily, while the duration and interval were modified according to the medical condition of each patient. The default delivery schedule, the mean number of S-1 cycles, did not differ significantly between the two age groups (<70 and ≥70 years). The rate of therapy discontinuation, schedule modification or dose reduction due to intolerable toxicities or patient refusal was relatively frequent in the older group (40.7 and 55.6% for ages <70 and ≥70 years, respectively; p=0.414), and the incidence of grade 3 anemia was relatively high in the older group (3.7 and 18.5%, respectively; p=0.192). The response rates (13.0 and 4.8%, respectively; p=0.609) and disease control rates (39.1 and 33.3%, respectively; p=0.761) did not differ significantly between the two age groups. According to histopathological type, the disease control rate was significantly higher in adenocarcinoma (57.9%) compared to non-adenocarcinoma (20.0%, p=0.013). Thus, S-1 monotherapy may be equally effective and tolerated in patients <70 years and those ≥70 years. Additionally, adenocarcinoma may have a higher disease control rate than non-adenocarcinoma.

Interferon Therapy For Elderly Egyptian Patients With Chronic Hepatitis C of Genotype 4

Background and study aim: Hepatitis C (HCV) affects nearly one in every 5 Egyptians which is the highest incidence allover the world. Most of the Egyptian Chronic Hepatitis (CHC) patients are of genotype 4 where it represents 90% of all Egyptian HCV cases. The clinical utility of antiviral therapy in elderly patients in our locality is not clear, also little information is available in literatures allover the world on treatment of such group of patients with genotype 4. The present study aimed at evaluating the efficacy and safety of combination therapy (pegylated interferon alpha 2a (PegIFN-alph2a) and ribavirin) in treatment of elderly Egyptian patients with HCV genotype 4. Patients and methods: 60 elderly Egyptian patients (more than 55years) with chronic HCV (group 1) and another group of 72 younger (less than 55 years) age patients (group 2) were enrolled in the present study. Both group of patients were compensated and all of genotype 4. Both groups received 180 mcg PegIFN-alpha2a subcutaneously once weekly and ribavirin (1000-1200mg/daily) for 48 weeks. Patients were followed for 48 weeks and sustained virological response and safety were assessed in both groups. Results : A significant improvement in both end of treatment response (ETR) and sustained virologic response (SVR) was noted in both group, where ETR was achieved in 32 (53.3%) and 41 patients (56.9%) in both groups respectively, and 27 patients in group 1 (45.0%) and 38 (52.8%) in group 2 could retain negative viraemia SVR by the end of follow up period. SVR showed a non-significant negative correlation with age. Viral clearance after 4weeks of therapy was associated with high incidence of ETR and SVR (P <0.001), but without significant difference between both groups. Rate of discontinuation and periods of discontinuation and side effect and safety of therapy was not significantly different in both groups. Conclusion : Despite these challenges, the present study showed that HCV treatment was generally well tolerated by the elderly Egyptian patients (55-68 years) with a little or no significant difference in SVR as well as therapy discontinuation rates secondary to adverse effects compared to younger age groups. Therefore, we recommend that chronic HCV Egyptian patients of age 55 years and more should be included in trials of chronic hepatitis C treatment and old age is no more contraindication for interferon/ribavirin therapy and the risk-benefit of antiviral therapy should be assessed on an individual basis.

Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment

AbstractWe assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP. This study is registered at http://www.clinicaltrials.gov as NCT01063179.

Patterns of Therapy Switching, Augmentation, and Discontinuation After Initiation of Treatment With Select Medications in Patients With Osteoarthritis

Background Osteoarthritis (OA) is a debilitating condition characterized by chronic pain. Several pain medications are recommended, and patients frequently alternate among these medications. Objectives The purpose of this study was to examine the use of pain medications in clinical practice with respect to recommended guidelines. This objective was accomplished by evaluating patterns of switching, augmentation, and discontinuation after treatment initiation with select medications in patients with OA. Methods The LifeLink Health Plan Claims Database was used to select patients with OA ( International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 715.XX) who were newly prescribed (index event) nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, acetaminophen, tramadol, weak opioids, and strong opioids. Descriptive statistics, Kaplan-Meier analyses, and the COX proportional hazards model were used to assess therapy switching, augmentation, and discontinuation during the 12-month postindex period. Patterns of intraarticular injections and joint replacement surgeries among the cohorts were also evaluated. Results Substantial proportions of OA patients switched, augmented, or discontinued therapy during the postindex period. Rates of therapy switching, augmentation, and discontinuation, respectively, were significantly different (all P < 0.0001 for overall effects using log-rank tests) across the evaluated medication cohorts: NSAIDs, 22.3%, 6.7%, 93.2%; COX-2 inhibitors, 27.5%, 10%, 87.4%; acetaminophen, 46.0%, 6.5%, 98.7%; tramadol, 44.5%, 8.4%, 95.6%; weak opioids, 27.2%, 4.1%, 98.3%; and strong opioids, 41.1%, 3.3%, 97%. Therapy switching, augmentation, and discontinuation occurred within 2 months after treatment initiation in two thirds of patients and within 6 months in >90% of patients. The patterns of intraarticular injections were significantly different across treatment cohorts, as were the patterns of joint replacement surgeries (both P < 0.0001 for overall effects using log-rank tests), with average times to surgery that appeared longer with acetaminophen, NSAIDs, and COX-2 inhibitor initiators (416–447 days) than with tramadol and opioids (354–385 days). Conclusions Results indicate that therapy switching and discontinuation were frequent among OA patients initiating treatment with the currently recommended medication classes and might suggest suboptimal pain relief or potentially intolerable therapy-related side effects.

Long-Term Chronic Opioid Therapy Discontinuation Rates from the TROUP Study

To report chronic opioid therapy discontinuation rates after five years and identify factors associated with discontinuation. Medical and pharmacy claims records from January 2000 through December 2005 from a national private health network (HealthCore), and Arkansas (AR) Medicaid were used to identify ambulatory adult enrollees who had 90days of opioids supplied. Recipients were followed until they discontinued opioid prescription fills or disenrolled. Kaplan Meier survival models and Cox proportional hazards models were estimated to identify factors associated with time until opioid discontinuation. There were 23,419 and 6,848 chronic opioid recipients followed for a mean of 1.9 and 2.3years in the HealthCore and AR Medicaid samples. Over a maximum follow up of 4.8years, 67.0% of HealthCore and 64.9% AR Medicaid recipients remained on opioids. Recipients on high daily opioid dose (greater than 120milligrams morphine equivalent (MED)) were less likely to discontinue than recipients taking lower doses: HealthCore hazard ratio (HR) = 0.66 (95%CI: 0.57-0.76), AR Medicaid HR = 0.66 (95%CI: 0.50-0.82). Recipients with possible opioid misuse were also less likely to discontinue: HealthCore HR = 0.83 (95%CI: 0.78-0.89), AR Medicaid HR = 0.78 (95%CI: 0.67-0.90). Over half of persons receiving 90days of continuous opioid therapy remain on opioids years later. Factors most strongly associated with continuation were intermittent prior opioid exposure, daily opioid dose ≥ 120mg MED, and possible opioid misuse. Since high dose and opioid misuse have been shown to increase the risk of adverse outcomes special caution is warranted when prescribing more than 90days of opioid therapy in these patients.

An economic analysis of antiviral therapy in patients with advanced hepatitis C virus disease: still not there!

An economic analysis of antiviral therapy in patients with advanced hepatitis C virus disease: still not there!

Pediatric gastroesophageal reflux disease and acid-related conditions: trends in incidence of diagnosis and acid suppression therapy

Objective: To describe the incidence of diagnosis of gastroesophageal reflux disease and acid-related conditions (GERD/ARC) throughout childhood and characterize patterns of diagnosis and treatment with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs).Methods: Cohorts of GERD/ARC children (age 0–18 years) were identified from a large US administrative claims database covering 1999–2005 using ICD-9 codes. Incidence, healthcare utilization (HCU), costs, therapy discontinuation and switching rates were compared between various age and patient groups.Results: Between 2000 and 2005 annual incidence of GERD/ARC diagnosis among infants (age ≤1 year) more than tripled (from 3.4 to 12.3%) and increased by 30% to 50% in other age groups. Patients diagnosed by GI specialists (9.2%) were more likely to be treated with PPIs compared to patients diagnosed by primary care physician (PCP). PPI-initiated patients doubled (from 31.5% in 1999 to 62.6% in 2005) and, when compared with H2RA-initiated patients, were associated with 30% less discontinuation and 90% less therapy switching in the first month, and with higher comorbidity burden and pre-treatment total HCU and costs when diagnosed by GI specialists.Limitations: The use of an exploratory definition for GERD/ARC, administrative claims data and potential coding errors in diagnosis codes used in selection process may limit the generalizability of the results.Conclusions: GERD/ARC incidence increased for children of all ages between 2000 and 2005. PCPs made the majority of diagnoses. PPI initiations have now surpassed H2RA initiations.