SWITCHING TREATMENT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FROM BEVACIZUMAB TO RANIBIZUMAB: Who is Likely to Benefit From the Switch?

PURPOSE: To evaluate the safety and efficacy of switching from bevacizumab to ranibizumab in patients with neovascular age-related macular degeneration. METHODS: Retrospective study of patients with neovascular age-related macular degeneration initially treated with bevacizumab and switched to ranibizumab. Visual acuity and central retinal thickness (CRT) were retrieved at four time points: before the last three bevacizumab injections, at the switch, after the first three ranibizumab injections, and at the end of follow-up. RESULTS: One hundred and fourteen eyes of 110 patients were included. Switching from bevacizumab to ranibizumab did not achieve a significant change in visual acuity, and a significant reduction in CRT was achieved after the first three injections but was not maintained by the end of follow-up. Eyes that lost ≥0.1 logMAR before the switch were more likely to improve in visual acuity (P = 0.013), and eyes with ≥10% increase in CRT before the switch were more likely to improve anatomically (P = 0.0003). In 47.3% of the eyes, the CRT was reduced by ≥10% after the first 3 ranibizumab injections, and the reduction was maintained with additional injections. CONCLUSION: Switching to ranibizumab should be considered in patients with visual acuity decrease or CRT increase, despite monthly bevacizumab injections. The response should be evaluated after the first three injections to guide future treatment.

Muscle pain and serum creatine kinase are not associated with low serum 25(OH) vitamin D levels in patients receiving statins.

OBJECTIVE: Vitamin D deficiency has been associated in some studies with nonspecific musculoskeletal pain and, more specifically, with statin-induced myalgia, which was ameliorated by high-dose vitamin D supplements. Our objective was to explore the association between vitamin D status and statin-induced myalgia and elevation of serum creatine kinase (CK). DESIGN: Retrospective cohort study, based on the electronic database of a health maintenance organization. PATIENTS: Six thousand eight hundred and eight patients (71·5% women) to whom statins were dispensed during 2008 and who had ≥1 CK and 25-hydroxy vitamin D (25OHD) levels measured during statin exposure. Of these, 376 patients (5·5%) had switched from a first-line statin to atorvastatin because of muscle pain (n = 220) or other reasons (n = 156). Measurements; In the entire cohort, we compared serum CK levels among serum 25OHD quartiles. In addition, we compared CK and 25OHD levels among patients with myalgia, other switchers and nonswitchers. RESULTS: The median 25OHD level in the entire cohort was 21·8 ng/ml [interquartile range (IQR), 16·3-27·4]. CK levels were marginally lower in patients in the lowest 25OHD quartile [median CK (IQR) in 25OHD quartiles 1-4, 87 (61-130), 90 (65-131), 91 (65-132) and 91 (67-131) IU/ml, respectively; P = 0·007]. 25OHD levels in statin switchers were similar to those in nonswitchers; moreover, there were no differences in 25OHD among switchers with muscle pain and other switchers. CONCLUSION: Our findings do not support an association between low 25OHD levels and statin-induced myalgia or CK elevation.

[The implementation of innovative medical technologies: biological pharmaceuticals for the treatment of psoriasis--a case study].

Advanced health systems worldwide strive to adopt new technologies that will ensure improved health and better clinical outcomes. The implementation of new medical technologies is affected by medical factors as well as economic and social forces, influencing both the individual and the health care providers. Chronic disease management is a major challenge to governments, as a result of the cumulative effects of chronic morbidity, life expectancy, quality of life and the national burden of disease due to accelerating medical expenditure. Psoriasis, a common chronic disease, for which advanced technologies were recently implemented, was chosen as a case study. The distribution of utility of various technologies for the treatment of psoriasis over the past nine years was analyzed to categorize "patterns of behavior" in accordance with the lifecycle of medical technology described in the Literature. It is expected that these changing trends will produce overall economic consequences, on direct expenditure combined with a reduction in some health services. Analyzing these clinical and economic trends, may add important considerations for the adoption of emerging medical technologies, presenting an important tool for policymakers at at all levels.

Brand versus generic alendronate: gastrointestinal effects measured by resource utilization.

BACKGROUND: Adverse reactions related to the upper gastrointestinal tract (UGIT) that are associated with generic alendronate formulations may differ from those associated with the brand drug. OBJECTIVE: To test the hypothesis that adverse UGIT effects of alendronate formulations may differ between generic and brand products. METHODS: We conducted a database health resource utilization analysis of UGIT outcomes in patients who started treatment with generic or brand alendronate formulations during 2001-2005. We included 6962 patients who were treated continuously for 3 months with 1 of 4 alendronate formulations: brand 10 mg/day (Merck, Sharpe & Dohme, n = 1418), generic A 10 mg/day (Teva, Israel, n = 650), generic B 10 mg/day (Unipharm, Israel, n = 628), and brand 70 mg/wk (n = 4266). In these patients, who had neither filled a prescription for alendronate nor had any gastrointestinal problems in the year preceding the study, we compared incidence rates of new use of gastric medications (H2-blockers, proton-pump inhibitors, or antacids), gastroenterology visits, endoscopies, and hospital admissions. RESULTS: Incident rate ratios (IRR) for treatment discontinuation were higher with both daily generic products (IRR 1.3; 95% CI 1.04 to 1.63). Adherence (medication possession ratio [MPR] >80%) was better with brand 10 mg/day (IRR 1.19; 95% CI 1.11 to 1.27). All comparisons were adjusted for use of concurrent corticosteroids, nonsteroidal antiinflammatory drugs, and potassium supplements. Hospitalization rates (2.7-3.2%) were similar in all groups. New use of gastric medications (3.4-4.9%) was lower with brand 10 mg/day (IRR 0.71; 95% CI 0.53 to 0.95). Rates of UGIT endoscopy (n = 49) in patients receiving 10 mg were 0.6% (brand), 1.1% (generic A), and 1.6% (generic B), with generic B higher (IRR 2.88; 95% CI 1.14 to 7.29) in the entire cohort, but not among new users (n = 273) of gastric drugs (IRR 2.46; 95% CI 0.55 to 11.05). Endoscopic findings were normal in 22 patients, hiatal hernia with no mucosal lesion was present in 10 patients, and there was mild-to-moderate esophagitis or gastritis in 17 patients; there were no significant differences among the formulations. CONCLUSIONS: We found insufficient evidence to indicate major differences in UGIT adverse effects related to use of daily generic, as compared with brand, alendronates.

Ranibizumab for persistent diabetic macular edema after bevacizumab treatment.

PURPOSE: To evaluate the efficacy of switching from bevacizumab to ranibizumab in patients with diabetic macular edema (DME). METHODS: This was a retrospective study of patients with DME initially treated with bevacizumab and switched to ranibizumab. Visual acuity (VA) and central retinal thickness (CRT) were retrieved at fixed timepoints prior to and after the switch. RESULTS: Forty eyes of 32 patients were included in the study. The difference in VA between any of these fixed timepoints was not statistically significant. A significant gain in VA was found in eyes that lost more than 0.1 logMAR during treatment with the last 3 bevacizumab injections. The mean CRT was significantly lower after the first 3 ranibizumab injections and at the final follow-up (p<0.001), a 67 ± 14 µm and 78 ± 18 µm reduction in thickness, respectively. CONCLUSIONS: Switching to ranibizumab resulted in a significant decrease in the CRT of eyes with DME, and should be considered when there is a lack of response or deterioration while on bevacizumab injections. A significant gain in VA was observed in a subgroup of eyes that lost more than one line while receiving the last 3 bevacizumab injections prior to the switch.

Hyperkalemia and renal function during monotherapy and dual renin-angiotensin blockade in the community setting.

BACKGROUND: In controlled trials, dual therapy with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) is associated with hyperkalemia and decreased renal function, but there is no information about these adverse effects in clinical practice. OBJECTIVE: The aim of this study was to assess the incidence of hyperkalemia and decreased renal function during dual therapy (ACE-I plus ARB) in a community-based setting. METHODS: In a retrospective cohort database study, we identified patients who received ARBs added to ongoing ACE-I therapy and who had at least 1 measurement of serum creatinine and potassium during each treatment period. We compared rates of hyperkalemia (>5.5 mmol/L) during equal periods of monotherapy and dual therapy and the rate of a significant rise in serum creatinine (≥0.5 mg/dL) between study periods. We assessed the impact of potential confounders on outcomes by logistic regression analysis. RESULTS: Among 425 patients (median follow-up 19 months for each treatment period), hyperkalemia was 2-fold more common during dual therapy than monotherapy (11.1% and 5.6% of patients, respectively) (relative risk = 1.96; 95% CI, 1.22-3.14; P < 0.001). In 77 patients with reduced renal function on monotherapy (serum creatinine ≥1.5 mg/dL), the rate of hyperkalemia was 20.8/100 patient-years, resulting in a number needed to harm of 10.1 patients, compared with 52.6 patients among those with preserved renal function. Mean serum creatinine between treatment periods increased >0.5 mg/dL in 7.5% of patients, more commonly in patients with decreased (18.2%) than with preserved (5.2%) baseline renal function (P < 0.001). CONCLUSION: In the community setting, dual therapy was associated with hyperkalemia and a decrease in renal function. The absolute risks were especially high among patients with reduced baseline renal function.