Pregnancy snapshot: a retrospective, observational case-control study to evaluate the potential effects of maternal diabetes treatment during pregnancy on macrosomia.

OBJECTIVE: Pregnancy in women with diabetes is associated with increased incidence of macrosomia (high birth weight) versus women without diabetes. Macrosomia increases the risk of complications during delivery and neonatally. The potential effect on macrosomia incidence certain diabetes treatments may have is not fully established. This study aims to identify whether specific components of the prenatal care of mothers with diabetes are associated with increased macrosomia risk in a real-world U.S. RESEARCH DESIGN AND METHODS: Retrospective, observational case-controlled study of mothers either without diabetes, or with type 1 (T1D), type 2 (T2D), or gestational diabetes mellitus (G.D.M.), using data from a U.S. insurance claims database. Treatment selection was at physician discretion. MAIN OUTCOME MEASURE: Incidence of macrosomia. RESULTS: For mothers with T2D, use of neutral protamine Hagedorn (N.P.H.) insulin and glyburide increased during pregnancy, from 3.4% to 33.3%, and 3.7% to 16.5%, respectively. The most common G.D.M. treatments during pregnancy were glyburide (15.5%), N.P.H. (12.9%), basal-bolus therapy (10.0%), and metformin (8.1%). Endocrinologist care during pregnancy was associated with insulin use - but not glyburide use - for mothers with G.D.M., and with insulin use for mothers with T1D and T2D (compared with mothers not visiting an endocrinologist). Glyburide was associated with higher odds for macrosomia: G.D.M. (odds ratio [O.R.] 1.53, 95% confidence interval [C.I.] 1.38-1.69, p < 0.0001); T2D (O.R. 1.93, 95% C.I. 1.51-2.47, p < 0.0001). Endocrinologist care was associated with lower odds for macrosomia overall (O.R. 0.86, 95% C.I. 0.81-0.92) and for mothers with G.D.M. (O.R. 0.85, 95% C.I. 0.75-0.97, p = 0.0156) when the sub-populations were examined in separate models. CONCLUSIONS: Healthcare utilization and endocrinologist care were related to positive birth outcomes, especially with G.D.M. Further research into the safety and efficacy of glyburide in pregnancy is warranted. This study cannot infer causality and may not be representative of current U.S. healthcare practice.

Early treatment revisions by addition or switch for type 2 diabetes: impact on glycemic control, diabetic complications, and healthcare costs.

BACKGROUND: The study examined the prevalence of early treatment revisions after glycosylated hemoglobin (HbA1c) ≥9.0% (75 mmol/mol) and estimated the impact of early treatment revisions on glycemic control, diabetic complications, and costs. RESEARCH DESIGN AND METHODS: A retrospective cohort study of administrative claims data of plan members with type 2 diabetes and HbA1c ≥9.0% (75 mmol/mol) was completed. Treatment revision was identified as treatment addition or switch. Glycemic control was measured as HbA1c during 6-12 months following the first qualifying HbA1c ≥9.0% (75 mmol/mol) laboratory result. Complications severity (via Diabetes Complication Severity Index (DCSI)) and costs were measured after 12, 24, and 36 months. Unadjusted comparisons and multivariable models were used to examine the relationship between early treatment revision (within 90 days of HbA1c) and outcomes after controlling for potentially confounding factors measured during a 12-month baseline period. RESULTS: 8463 participants were included with a mean baseline HbA1c of 10.2% (75 mmol/mol). Early treatment revision was associated with greater reduction in HbA1c at 6-12 months (-2.10% vs -1.87%; p<0.001). No significant relationship was observed between early treatment revision and DCSI at 12, 24, or 36 months (p=0.931, p=0.332, and p=0.418). Total costs, medical costs, and pharmacy costs at 12, 24, or 36 months were greater for the early treatment revision group compared with the delayed treatment revision group (all p<0.05). CONCLUSIONS: The findings suggest that in patients with type 2 diabetes mellitus, treatment revision within 90 days of finding an HbA1c ≥9.0% is associated with a greater level of near-term glycemic control and higher cost. The impact on end points such as diabetic complications may not be realized over relatively short time frames.

Reporting error in weight and its implications for bias in economic models.

Most research on the economic consequences of obesity uses data on self-reported weight, which contains reporting error that has the potential to bias coefficient estimates in economic models. The purpose of this paper is to measure the extent and characteristics of reporting error in weight, and to examine its impact on regression coefficients in models of the healthcare consequences of obesity. We analyze data from the National Health and Nutrition Examination Survey (NHANES) for 2003-2010, which includes both self-reports and measurements of weight and height. We find that reporting error in weight is non-classical: underweight respondents tend to overreport, and overweight and obese respondents tend to underreport, their weight, with underreporting increasing in measured weight. This error results in roughly 1 out of 7 obese individuals being misclassified as non-obese. Reporting error is also correlated with other common regressors in economic models, such as education. Although it is a common misconception that reporting error always causes attenuation bias, comparisons of models that use self-reported and measured weight confirm that reporting error can cause upward bias in coefficient estimates. For example, use of self-reports leads to overestimates of the probability that an obese man uses a prescription drug, has a healthcare visit, or has a hospital admission. These findings underscore that models of the consequences of obesity should use measurements of weight, when available, and that social science datasets should measure weight rather than simply ask subjects to report their weight.

The dynamic relationship between current and previous severe hypoglycemic events: a lagged dependent variable analysis among patients with type 2 diabetes who have initiated basal insulin.

BACKGROUND AND OBJECTIVE: Past studies have found episodes of severe hypoglycemia (SH) to be serially dependent. Those studies, however, only considered the impact of a single (index) event on future risk; few have analyzed SH risk as it evolves over time in the presence (or absence) of continuing events. The objective of this study was to determine the dynamic risks of SH events conditional on preceding SH events among patients with type 2 diabetes (T2D) who have initiated basal insulin. METHODS: We used an electronic health records database from the United States that included encounter and laboratory data and clinical notes on T2D patients who initiated basal insulin therapy between 2008 and 2011 and to identify SH events. We used a repeated-measures lagged dependent variable logistic regression model to estimate the impact of SH in one quarter on the risk of SH in the next quarter. RESULTS: We identified 7235 patients with T2D who initiated basal insulin. Patients who experienced ≥1 SH event during any quarter were more likely to have ≥1 SH event during the subsequent quarter than those who did not (predicted probabilities of 7.4% and 1.0%, respectively; p < 0.01). This effect was stronger than the impact of history of SH before starting basal insulin (predicted probabilities of 1.0% and 3.2%, respectively; p < 0.01) or of a history of SH during the titration period (predicted probabilities of 1.1% and 2.8%, respectively; p < 0.01). CONCLUSIONS: The risk of experiencing a SH event is highly dependent on a patient's immediate history of SH events and therefore the value of preventing one SH event may be substantial. These results can inform patient care by providing clinicians with dynamic data on a patient's risk of SH, which in turn can facilitate appropriate adjustment of the risk-benefit ratio for individualized patient care. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, we were unable to adjust for basal insulin dose, and the post-titration follow-up period could have divided into time units other than quarters (3 month blocks) resulting in potentially different conclusions. Further real-world studies on how to best to identify patients at risk for SH events based on the presence of recent SH events, rather than on more distant 'prior' events, can help healthcare providers to better manage patients starting basal insulin.

Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy.

BACKGROUND: Increasing diabetes prevalence affects a substantial number of pregnant women in the United States. Our aims were to evaluate health outcomes, medical costs, risks and types of complications associated with diabetes in pregnancy for mothers and newborns. METHODS: In this retrospective claims analysis, patients were identified from the Truven Health MarketScan(®) database (2004-2011 inclusive). Participants were aged 18-45 years, with ascertainable diabetes status [Yes/No], date of birth event >2005 and continuous health plan enrolment ≥21 months before and 3 months after the birth. RESULTS: In total, 839 792 pregnancies were identified, and 66 041 (7.86%) were associated with diabetes mellitus [type 1 (T1DM), 0.13%; type 2 (T2DM), 1.21%; gestational (GDM), 6.29%; and GDM progressing to T2DM (patients without prior diabetes who had a T2DM diagnosis after the birth event), 0.23%]. Relative risk (RR) of stillbirth (2.51), miscarriage (1.28) and Caesarean section (C-section) (1.77) was significantly greater with T2DM versus non-diabetes. Risk of C-section was also significantly greater for other diabetes types [RR 1.92 (T1DM); 1.37 (GDM); 1.63 (GDM progressing to T2DM)]. Risk of overall major congenital (RR ≥ 1.17), major congenital circulatory (RR ≥ 1.19) or major congenital heart (RR ≥ 1.18) complications was greater in newborns of mothers with diabetes versus without. Mothers with T2DM had significantly higher risk (RR ≥ 1.36) of anaemia, depression, hypertension, infection, migraine, or cardiac, obstetrical or respiratory complications than non-diabetes patients. Mean medical costs were higher with all diabetes types, particularly T1DM ($27 531), than non-diabetes ($14 355). CONCLUSIONS: Complications and costs of healthcare were greater with diabetes, highlighting the need to optimize diabetes management in pregnancy.

Savings in Medical Expenditures Associated with Reductions in Body Mass Index Among US Adults with Obesity, by Diabetes Status.

BACKGROUND: The prevalence of obesity has more than doubled in the USA in the past 30 years. Obesity is a significant risk factor for diabetes, cardiovascular disease, and other clinically significant co-morbidities. This paper estimates the medical care cost savings that can be achieved from a given amount of weight loss by people with different starting values of body mass index (BMI), for those with and without diabetes. This information is an important input into analyses of the cost effectiveness of obesity treatments and prevention programs. METHODS: Two-part models of instrumental variables were estimated using data from the Medical Expenditure Panel Survey (MEPS) for 2000-2010. Models were estimated for all adults as well as separately for those with and without diabetes. We calculated the causal impact of changes in BMI on medical care expenditures, cost savings for specific changes in BMI (5, 10, 15, and 20 %) from starting BMI levels ranging from 30 to 45 kg/m(2), as well as the total excess medical care expenditures caused by obesity. RESULTS: In the USA, adult obesity raised annual medical care costs by $US3,508 per obese individual, for a nationwide total of $US315.8 billion (year 2010 values). However, the relationship of medical care costs over BMI is J-shaped; costs rise exponentially in the range of class 2 and 3 obesity (BMI ≥35). The heavier the obese individual, the greater the reduction in medical care costs associated with a given percent reduction in BMI. Medical care expenditures are higher, and rise more with BMI, among individuals with diabetes than among those without diabetes. CONCLUSIONS: The savings from a given percent reduction in BMI are greater the heavier the obese individual, and are greater for those with diabetes than for those without diabetes. The results provide health insurers, employers, government agencies, and health economists with accurate estimates of the change in medical care expenditures resulting from weight loss, which is important information for calculating the cost effectiveness of interventions to prevent and treat obesity.

Value of lifestyle intervention to prevent diabetes and sequelae.

BACKGROUND: The Community Preventive Services Task Force recommends combined diet and physical activity promotion programs for people at increased risk of type 2 diabetes, as evidence continues to show that intensive lifestyle interventions are effective for overweight individuals with prediabetes. PURPOSE: To illustrate the potential clinical and economic benefits of treating prediabetes with lifestyle intervention to prevent or delay onset of type 2 diabetes and sequelae. METHODS: This 2014 analysis used a Markov model to simulate disease onset, medical expenditures, economic outcomes, mortality, and quality of life for a nationally representative sample with prediabetes from the 2003-2010 National Health and Nutrition Examination Survey. Modeled scenarios used 10-year follow-up results from the lifestyle arm of the Diabetes Prevention Program and Outcomes Study versus simulated natural history of disease. RESULTS: Over 10 years, estimated average cumulative gross economic benefits of treating patients who met diabetes screening criteria recommended by the ADA ($26,800) or USPSTF ($24,700) exceeded average benefits from treating the entire prediabetes population ($17,800). Estimated cumulative, gross medical savings for these three populations averaged $10,400, $11,200, and $6,300, respectively. Published estimates suggest that opportunistic screening for prediabetes is inexpensive, and lifestyle intervention similar to the Diabetes Prevention Program can be achieved for ≤$2,300 over 10 years. CONCLUSIONS: Lifestyle intervention among people with prediabetes produces long-term societal benefits that exceed anticipated intervention costs, especially among prediabetes patients that meet the ADA and USPSTF screening guidelines.

The economic burden of elevated blood glucose levels in 2012: diagnosed and undiagnosed diabetes, gestational diabetes mellitus, and prediabetes.

OBJECTIVE: To update estimates of the economic burden of undiagnosed diabetes, prediabetes, and gestational diabetes mellitus in 2012 in the U.S. and to present state-level estimates. Combined with published estimates for diagnosed diabetes, these statistics provide a detailed picture of the economic costs associated with elevated glucose levels. RESEARCH DESIGN AND METHODS: This study estimated health care use and medical expenditures in excess of expected levels occurring in the absence of diabetes or prediabetes. Data sources that were analyzed include Optum medical claims for ∼4.9 million commercially insured patients who were continuously enrolled from 2010 to 2012, Medicare Standard Analytical Files containing medical claims for ∼2.6 million Medicare patients in 2011, and the 2010 Nationwide Inpatient Sample containing ∼7.8 million hospital discharge records. The indirect economic burden includes reduced labor force participation, missed workdays, and reduced productivity. State-level estimates reflect geographic variation in prevalence, risk factors, and prices. RESULTS: The economic burden associated with diagnosed diabetes (all ages) and undiagnosed diabetes, gestational diabetes, and prediabetes (adults) exceeded $322 billion in 2012, consisting of $244 billion in excess medical costs and $78 billion in reduced productivity. Combined, this amounts to an economic burden exceeding $1,000 for each American in 2012. This national estimate is 48% higher than the $218 billion estimate for 2007. The burden per case averaged $10,970 for diagnosed diabetes, $5,800 for gestational diabetes, $4,030 for undiagnosed diabetes, and $510 for prediabetes. CONCLUSIONS: These statistics underscore the importance of finding ways to reduce the burden of prediabetes and diabetes through prevention and treatment.

The association between nonadherence and glycated hemoglobin among type 2 diabetes patients using basal insulin analogs.

BACKGROUND: The main objective of this study was to investigate the relationship between adherence and both clinical (ie, glycated hemoglobin [HbA1c]) and nonclinical (ie, health status, work impairment, and health care-resource use) health outcomes among type 2 diabetes (T2D) patients using basal insulin. MATERIALS AND METHODS: The 2012 US National Health and Wellness Survey dataset was used for this study (n=71,141). A total of 1,198 respondents who reported a diagnosis of T2D, were currently using basal insulin, and reported both their HbA1c and level of nonadherence were included in the analyses. Classical test theory and item response theory (IRT) analyses were used to provide evidence for the Morisky Medication Adherence Scale (MMAS) in this population. Adherence was then used as a predictor of HbA1c and nonclinical outcomes using regression modeling, controlling for demographics and health history. RESULTS: A total of 61.44% of respondents were male, and the mean age was 60.65 (standard deviation 10.74) years. Internal consistency of the eight-item MMAS (MMAS-8) was adequate (Cronbach's α =0.68), and one factor was retained (eigenvalue =1.80). IRT analyses suggested that the MMAS-8 was most precise for those with high levels of nonadherence. A significant relationship between variables emerged, whereby each point increase in the level of nonadherence was associated with a 0.21 increase in HbA1c (B=0.212, P<0.05). A modest quadratic trend was also observed (B=0.026, P<0.05), indicating that the benefit to HbA1c may taper off at high adherence. Each point of nonadherence was associated with a 4.6%, 20.4%, and 20.9% increase in the number of physician visits, emergency room visits, and hospitalizations, respectively. DISCUSSION: This study provides evidence that adherence rates are high among patients with T2D using basal insulin, and the MMAS-8 is a reliable and valid tool to assess adherence. Further, the results suggest that HbA1c increases concomitantly with nonadherence, as do poorer health status and health care-resource use.

Severe hypoglycemia rates and associated costs among type 2 diabetics starting basal insulin therapy in the United States.

OBJECTIVES: To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. METHODS: We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. RESULTS: We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p < 0.01). Regression-adjusted total healthcare and diabetes-related costs were statistically significantly (p < 0.01) higher in those quarters when a SH event occurred than in those quarters without any SH events ($3591 vs. $487 and $3311 vs. $406, respectively). A history of previous SH or SH events during the titration period were not statistically significantly associated with costs. CONCLUSIONS: These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, and the post-titration follow-up period could have been divided into time units other than quarters (3 month blocks) resulting in potentially different conclusions. Further real-world studies on the frequency and costs of SH, using methods to identify as many SH events as possible, can allow healthcare providers to make more informed decisions on the risks and benefits of basal insulin therapy in T2D patients.

The association of body mass index with the risk of type 2 diabetes: a case-control study nested in an electronic health records system in the United States.

OBJECTIVES: Obesity is a known risk factor for type 2 diabetes (T2D). We conducted a case-control study to assess the association between body mass index (BMI) and the risk of being diagnosed with T2D in the United States. METHODS: We selected adults (≥ 18 years old) who were diagnosed with T2D (defined by ICD-9-CM diagnosis codes or use of anti-diabetic medications) between January 2004 and October 2011 ("cases") from an electronic health records database provided by an integrated health system in the Middle Atlantic region. Twice as many individuals enrolled in the health system without a T2D diagnosis during the study period ("controls") were selected based on age, sex, history of cardiac comorbidities or hyperinflammatory state (defined by C-reactive protein and erythrocyte sedimentation rate), and use of psychiatric or beta blocker medications. BMI was measured during one year prior to the first observed T2D diagnosis (for cases) or a randomly assigned date (for controls); individuals with no BMI measure or BMI < 18.5 kg/m2 were excluded. We assessed the impact of increased BMI (overweight: 25-29.9 kg/m2; Obesity Class I: 30-34.9 kg/m2; Obesity Class II: 35-39.9 kg/m2; Obesity Class III: ≥40 kg/m2), relative to normal BMI (18.5-24.9 kg/m2), on a T2D diagnosis using odds ratios (OR) and relative risks (RR) estimated from multiple logistic regression results. RESULTS: We included 12,179 cases (mean age: 55, 43% male) and 25,177 controls (mean age: 56, 45% male). We found a positive association between BMI and the risk of a T2D diagnosis. The strength of this association increased with BMI category (RR [95% confidence interval]: overweight, 1.5 [1.4-1.6]; Obesity Class I, 2.5 [2.3-2.6]; Obesity Class II, 3.6 [3.4-3.8]; Obesity Class III, 5.1 [4.7-5.5]). CONCLUSIONS: BMI is strongly and independently associated with the risk of being diagnosed with T2D. The incremental association of BMI category on the risk of T2D is stronger for people with a higher BMI relative to people with a lower BMI.

Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheumatoid arthritis in Italy.

OBJECTIVE: This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer's perspective in Italy. METHODS: An individual patient simulation model was used to project lifetime medical costs (payer's perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis. RESULTS: Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient's lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY. CONCLUSION: The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.

Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: a retrospective medical records review.

AIMS: This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. MATERIALS AND METHODS: We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. RESULTS: Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). CONCLUSIONS: Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid.

Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.

OBJECTIVES: To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS: Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI). RESULTS: Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1). CONCLUSIONS: Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.

Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review.

PURPOSE: This retrospective study compared renal impairment rates in breast cancer, multiple myeloma, prostate cancer and non-small cell lung cancer patients treated with ibandronate or zoledronic acid. STUDY DESIGN: Medical records in two German oncology clinics from May 2001 to March 2006 were retrospectively reviewed. Creatinine measurements were analyzed from baseline (before bisphosphonate treatment) to last available measurement for each patient. The Cox proportional hazards model and the Andersen-Gill extension of the Cox model for multiple events analysis were used for multivariate analysis, which controlled for age, clinic site, primary cancer type, baseline SCr or GFR value, prior bisphosphonate use, concomitant use of drugs associated with acute renal failure, and renal-related comorbidities. RESULTS: Of 333 patients, 109 received ibandronate and 256 received zoledronic acid (32 patients had both drugs). Compared with ibandronate, the zoledronic acid group had a significantly better baseline renal function and fewer patients had a history of renal disease. Zoledronic acid treatment increased the relative risk (RR) and the incidence rate (IR) of renal impairment by approximately 1.5-fold in all assessed patients (all tumors) compared with ibandronate. Multivariate analysis found significantly higher hazards ratios for zoledronic acid over ibandronate (two to sixfold), after adjusting for differences in characteristics between the two treatment groups. CONCLUSIONS: In this retrospective review, patients were significantly more likely to experience renal impairment with zoledronic acid than with ibandronate.

Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a.

BACKGROUND/AIMS: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). METHOD: The HBV studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg-negative (n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 microg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. RESULTS: Differences (HBV vs HCV) were observed in the incidence of AEs (88-89 vs 96-100%), serious AEs (4-5 vs 7-16%) and treatment withdrawals (6-8 vs 17-33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. CONCLUSIONS: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression.

Cost-effectiveness of enfuvirtide in HIV therapy for treatment-experienced patients in the United States.

Enfuvirtide (ENF) is the first of a new class of antiretrovirals (ARVs) known as the HIV fusion inhibitors. Two phase III studies of ENF, TORO 1 and TORO 2, demonstrated that ENF given in combination with optimized background (OB) therapy significantly improved virological response, increased the time to virological failure, and increased CD4-cell count compared with OB alone among highly treatment-experienced patients. The present study investigated the long-term clinical outcomes, costs, and cost-effectiveness of ENF. Outcomes, costs, and cost-effectiveness were estimated using a Markov model. Viral suppression and immune reconstitution were determined from the outcomes of the clinical trials. Time to immunological failure, time to AIDS-defining event (ADE), and time to death were estimated based on published mathematical models of disease progression. Costs were based on published estimates of the use and costs of ARVs, cost of managing ADEs, and cost of laboratory and other outpatient services. Cost-effectiveness was calculated as the incremental cost per year of life gained, adjusted for quality of life. The combined effects of an increase in CD4 count and delayed time to virological and immunological failure with ENF + OB were predicted to produce a mean life expectancy of 7.4 years from initiation of therapy, which was 1.8 years (1.5 quality-adjusted lifeyears [QALYs]) greater than the life expectancy associated with OB alone. The incremental cost-effectiveness of ENF + OB was estimated to be Dollars 24,604 per QALY. ENF is projected to increase time to immunological failure, delay onset of new AIDS-defining events, and increase life expectancy by more than 1.5 years among treatment-experienced HIV-infected patients. The cost-effectiveness of ENF is comparable to many existing treatment and prevention management strategies for HIV.

Treatment of chronic hepatitis C patients with persistently normal alanine aminotransferase levels with the combination of peginterferon alpha-2a (40 kDa) plus ribavirin: impact on health-related quality of life.

BACKGROUND: Peginterferon alpha-2a (40 kDa) plus ribavirin is equally effective in chronic hepatitis C patients with normal or elevated alanine aminotransferase (ALT) values. This analysis, in patients with normal ALT levels, compared health-related quality of life (HRQoL) measurements between untreated control patients and treated patients grouped by virological response. HRQoL in the present population was also compared with HRQoL in patients with elevated ALT levels, observed in a previous study. METHODS: A total of 491 patients with persistently normal ALT levels were randomized to peginterferon alpha-2a (40 kDa)/ribavirin for 24 (group A) or 48 weeks (group B) or no treatment for 72 weeks (group C). Quality of life was assessed with valid instruments (self-administered Short Form (SF)-36 Health Survey and Fatigue Severity Scale). RESULTS: In groups A and B, patients with sustained virological responses after combination therapy had significantly better quality of life and less fatigue than patients without sustained responses. Differences were significant for five SF-36 domains, the SF-36 Physical Component score and both Fatigue Severity Scale scores. Viral clearance was not observed in any untreated patients (group C). Comparison with data from elevated ALT patients revealed little difference in baseline quality of life, although normal ALT patients had significantly higher scores related to mental health than elevated ALT patients. CONCLUSIONS: Eradication of HCV with peginterferon alpha-2a (40 kDa) plus ribavirin is associated with better quality of life and less fatigue in normal ALT patients. These patient benefits, coupled with the high probability of eradicating HCV, should be considered in making decisions about treating this population.

Cost-effectiveness of enfuvirtide for treatment-experienced patients with HIV in Italy.

BACKGROUND: Enfuvirtide (ENF) plus an optimized background (OB) antiretroviral regimen delays virological failure (VF), reduces HIV-1 viral load, and increases CD4 count compared with OB only in pretreated patients. PURPOSE: To forecast long-term outcomes, costs, and cost-effectiveness of ENF+OB vs. OB in the Italian health care system. METHOD: A Markov model was developed and clinical trial results on viral suppression and CD4 count were linked with data from HAART-era studies of the risk of AIDS-defining events (ADEs) and death. Resource data were obtained from Italian sources on direct medical costs. Cost-effectiveness was computed as the incremental cost per quality-adjusted life year (QALY) saved. RESULTS: Patients receiving ENF+OB were projected to experience a mean time to virological failure of 1.0 years vs. 0.5 years for OB and mean time to immunological failure of 3.1 years vs. 1.3 years for OB. Life expectancy and QALYs were greater for ENF+OB than OB by 1.8 and 1.5 years, respectively. Total lifetime medical cost was euro 126,487 for ENF+OB and euro 84,416 for OB, a difference of euro 42,071 due to the cost of ENF itself (euro 18,400) and the medical costs associated with additional life expectancy (euro 23,671). The incremental cost-effectiveness of ENF+OB was euro 23,721 per life year (euro 28,669 per QALY). CONCLUSION: ENF+OB is predicted to increase life expectancy at a cost per life year that is comparable to many well-accepted therapies in Europe.

Health-related quality of life with enfuvirtide (ENF; T-20) in combination with an optimized background regimen.

This study assessed the impact of enfuvirtide on health-related quality of life (HRQoL). Patients enrolled in 2 phase 3 trials T-20 versus Optimized Regimen Only (TORO 1 and 2) completed the Medical Outcomes Study (MOS)-HIV questionnaire at baseline and at 4, 8, 16, and 24 weeks. A total of 995 treatment-experienced HIV-1-infected individuals received either self-administered enfuvirtide (90 mg twice daily) + optimized background (OB) or OB alone and had at least 1 follow-up visit. Data from the 2 clinical trials were pooled. Analysis of covariance was used to evaluate changes in the 10 MOS-HIV scale scores and 2 summary scores. Least-squares means for these changes were calculated and used to test for between-group differences. There were no significant between-group differences in any HRQoL measure at baseline. Most MOS-HIV scores showed improvement in the enfuvirtide arm compared with OB alone, although only some of these were significant. Improvements in the general health scale were significantly higher in the enfuvirtide arm compared with OB alone at all post-baseline time points. No scale or summary score for the OB arm showed a significantly greater improvement in score from baseline compared with the enfuvirtide arm, at any time point. The mental health summary score at 24 weeks was significantly higher in the enfuvirtide arm compared with OB alone. Enfuvirtide in addition to an OB regimen does not adversely affect and may improve HRQoL when self-administered for up to 24 weeks by treatment-experienced, HIV-1-infected individuals.