Enzyme replacement therapy with velaglucerase alfa in Gaucher disease: Results from a randomized,double‐blind,multinational, Phase 3 study

Type 1 Gaucher disease (GD1), resulting from glucocerebrosidase deficiency, leads to splenomegaly, hepatomegaly, anemia, thrombocytopenia, and bone involvement. Current standard treatment is enzyme replacement therapy. Velaglucerase alfa is an enzyme replacement product for GD1, with the same amino acid sequence as naturally occurring human glucocerebrosidase. This multinational, Phase 3 trial evaluated the efficacy and safety of two doses of velaglucerase alfa in 25 treatment‐naïve, anemic patients with GD1 (4–62 years of age), randomized to intravenous velaglucerase alfa 60 U/kg (n=12) or 45 U/kg body weight (n=13) every other week for 12 months. The primary endpoint was change from baseline in hemoglobin concentration in the 60 U/kg arm. At 12 months, mean hemoglobin concentrations increased from baseline [60 U/kg: +23.3%; +2.43 g/dL (P<0.001); 45 U/kg: +23.8%; +2.44 g/dL (P<0.001)], as did mean platelet counts [60 U/kg: +65.9%; +50.9 × 10⁹/L (P=0.002); 45 U/kg: +66.4%; +40.9 × 10⁹/L(P=0.01)]. Mean splenic volume decreased from baseline [60 U/kg: ?50.4%, from 14.0 to 5.8 multiples of normal (MN) (P=0.003); 45 U/kg: ?39.9%, from 14.5 to 9.5 MN (P=0.009)]. No drug‐related serious adverse events or withdrawals were observed. One patient developed antibodies. Velaglucerase alfa was generally well tolerated and effective for adults and children with GD1 in this study. All disease‐specific parameters measured demonstrated clinically meaningful improvements after 12 months. Am. J. Hematol. 88:166–171, 2013. © 2012 Wiley Periodicals, Inc.     

Efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies: a randomized,double-blind,placebo-controlled study

This phase 3, randomized, double-blind, placebo-controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2.25 microg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0.001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1.80 g/dl vs 0.19 g/dl) and after 12 weeks of treatment (2.66 g/dl vs 0.69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0.001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.     

High Target Hemoglobin With Erythropoiesis‐Stimulating Agents Has Advantages in the Renal Function of Non‐Dialysis Chronic Kidney Disease Patients

We investigated the long‐term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2–6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.0 g/dL) receiving darbepoetin alfa or to a low Hb group (N = 160, 9.0 ≤ Hb < 11.0 g/dL) with epoetin alfa, stratified according to baseline Hb and serum Cr levels, comorbidity of diabetes, and study centers. Primary endpoints were composites of the following events: doubling of serum Cr, initiation of dialysis, renal transplantation, or death. Three‐year cumulative renal survival rates (95% CI) were 39.9% (30.7–49.1%) and 32.4% (24.0–40.8%) in the high and low Hb groups, respectively (log‐rank test; P = 0.111). A Cox proportional‐hazards model adjusted by age, sex and the randomization factors showed a significantly lower event rate in the high Hb group (P = 0.035). The estimated hazard ratio (95% CI) for the high versus the low Hb group was 0.71 (0.52–0.98), the risk reduction was 29% in the high Hb group. Incidences of serious adverse cardiovascular events did not differ significantly between the high and low Hb groups (3.1% and 4.4%, respectively). No safety issues were noted in either group. Maintaining higher Hb levels with darbepoetin alfa better preserved renal function in patients with chronic kidney disease not on dialysis.     

Low dose erythropoietin‐beta improves anemia and maintains ribavirin dose in chronic hepatitis C patients receiving combination therapy with ribavirin plus pegylated interferon Alfa‐2b

Aim: Anemia during combination therapy with pegylated interferon alfa‐2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin‐beta (EPO‐β) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy. Methods: Eighty‐eight chronic HCV patients who developed anemia during therapy were enrolled into this retrospective study: 55 in the EPO‐β group and 33 in the untreated group. The study endpoints were to assess the RBV maintenance and the changes in Hb. Results: A higher percentage of patients with RBV maintenance was observed in the EPO‐β group compared with the untreated group (nadir Hb level <10.5 g/dL; 70% vs. 38%, P = 0.020; nadir Hb < 10 g/dL; 62% vs. 27%, P = 0.046). The mean Hb change from week 12 to week 20 was higher in the EPO‐β group when compared with the untreated group, especially for patients receiving a total EPO‐β dose of more than 16 000 U (+0.70 g/dL vs. ?0.32 g/dL, P = 0.023) and of 10 000 U‐14 000 U (+0.60 g/dL vs. ?0.32 g/dL, P = 0.023). Conclusions: Low‐dose EPO‐β can maintain RBV dose and increase Hb levels in anemic chronic HCV patients receiving combination therapy.     

Long‐Term Safety and Efficacy of JR‐131, a Biosimilar of Darbepoetin Alfa,in Japanese Patients With Renal Anemia Undergoing Hemodialysis: Phase 3 Prospective Study

The objective of this study was to evaluate the safety and efficacy of JR‐131, a biosimilar of darbepoetin alfa, for long‐term treatment of renal anemia patients undergoing hemodialysis. In this multicenter, single‐arm, phase 3 study, 159 patients with renal anemia who had been receiving darbepoetin alfa or recombinant human erythropoietins were treated with intravenous JR‐131 for 52 weeks. In patients receiving darbepoetin alfa, JR‐131 was administered at the same dose, while in patients receiving recombinant human erythropoietin the dose was determined based on the 1:200 conversion ratio following the Japanese darbepoetin alfa package insert. No notable adverse drug reactions were reported, and no anti‐JR‐131 antibodies were detected. The hemoglobin levels were maintained in the range of 10.0–12.0 g/dL throughout the study. JR‐131 proved to be a useful and lower‐cost alternative to darbepoetin alfa in the management of renal anemia in patients undergoing hemodialysis.     

Randomized controlled trial of single‐agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes: A comparative study

Aims/Introduction: To compare first‐line, single‐agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes uncontrolled by diet and exercise with respect to glycemic control, safety and metabolic changes. Materials and Methods: Patients with previously untreated type 2 diabetes were enrolled in a multicenter, randomized, non‐blind, parallel‐group trial of glimepiride (0.5–6 mg/day) or pioglitazone (15–45 mg/day) for 6 months. Results: A total of 191 patients aged 30–75 years were randomized. Similar percentages of patients attained the primary end‐point, with glycated hemoglobin < 6.9% at month 6 with glimepiride and pioglitazone, respectively (61.2 vs 56.8%, P = 0.64). At month 6, the following significant (P < 0.05) intragroup changes in mean plasma lipid concentrations were noted as compared with baseline: total cholesterol decreased from 203.5 to 195.5 mg/dL and low‐density lipoprotein (LDL)‐cholesterol decreased from 124.5 to 116.3 mg/dL in the glimepiride group, whereas high‐density lipoprotein (HDL)‐cholesterol increased from 51.6 to 56.0 mg/dL and triglycerides decreased from 167.6 to 143.6 mg/dL in the pioglitazone group. The only symptomatic adverse events were mild‐to‐moderate in four patients receiving pioglitazone, and constipation in one patient receiving glimepiride. Similar numbers of patients experienced asymptomatic hypoglycemia (<60 mg/dL) in the glimepiride and pioglitazone groups (n = 7 and 5, respectively). Conclusions: There was no statistically significant difference between glimepiride and pioglitazone with respect to glycemic control, and both agents were well tolerated. Glimepiride significantly lowered total cholesterol and LDL‐cholesterol, whereas pioglitazone increased HDL‐cholesterol. This trial was registered with University Hospital Medical Information Network (UMIN), Japan, UMIN000004582. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00115.x, 2011)     

Efficacy of repeated intravenous infusions of an anti–tumor necrosis factor α monoclonal antibody,infliximab, in persistently active,refractory juvenile idiopathic arthritis: Results of an open‐label prospective study

Objective

To evaluate the efficacy and safety of a chimeric monoclonal anti–tumor necrosis factor α antibody (infliximab) with methotrexate (MTX) in juvenile idiopathic arthritis (JIA) with an active polyarticular course that is not responsive to MTX.

Methods

Twenty‐four young adults with long‐lasting, refractory JIA were enrolled in an open, prospective, 2‐year pilot study. Patients received intravenous infliximab at 3 mg/kg of body weight at weeks 0, 2, and 6 and every 8 weeks thereafter, with weekly subcutaneous MTX.

Results

The median duration of therapy was 9.1 months. Significant improvements were observed in the number of joints (28‐joint count) with active disease (median 6 at baseline, 2 at 2 weeks, 0 at 6 months, 0 at 1 year; P < 0.05). Pain as well as patient's and physician's global assessments of disease status were assessed on 0–100‐mm (0 = best; 100 = worst) visual analog scales (VAS). There were significant improvements in VAS pain scores (45 at baseline, 25 at 2 weeks, 8.5 at 6 months, 10 at 1 year; P < 0.05), patient's global assessment of disease status (50 at baseline, 22 at 2 weeks, 11.5 at 6 months, 18 at 1 year; P < 0.05), and physician's global assessment of disease status (50.5 at baseline, 22.5 at 2 weeks, 6.5 at 6 months, 10 at 1 year; P < 0.01). In addition, there were significant improvements in the erythrocyte sedimentation rate (64 mm/hour at baseline, 36 mm/hour at 2 weeks, 23.5 mm/hour at 6 months, 35 mm/hour at 1 year; P < 0.01) and C‐reactive protein level (4.9 mg/dl at baseline, 2.8 mg/dl at 2 weeks, 3.1 mg/dl at 6 months, 3.2 mg/dl at 1 year; P < 0.005). The percentage of patients meeting the American College of Rheumatology 20% improvement criteria at each assessment ranged from 54.2% to 86.7%. Of the responses on the Disease Activity Score in 28 joints, 37.5–63.6% were classified as “good,” 14.3–33.3% were classified as “moderate,” and 18–37.5% were classified as “no response.” Twelve patients (50%) had adverse events, and 5 patients (20.8%) withdrew.

Conclusion

Infliximab plus MTX showed high effectiveness and safety in short‐ and medium‐term treatment of long‐lasting refractory JIA. A controlled multicenter clinical trial is needed.

     

Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: A randomized case-controlled study

Background: Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO).

Aim of the study: To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy.

Patient and methods: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males and 13 females, age; 6.8 ± 2.33 years), or no epoetin alfa (control group = 30 cases, 16 males and 14 females, age; 6.76 ± 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters.

Results: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 ± 1.48 g/dl (p < 0.001). An increase in Hb of ≧ 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for ≧ 30 days. The overall response rate (Hb increase ≧ 2 g/dl or Hb ≧ 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-α therapy was found to significantly (p < 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-α was found to be well tolerated.

Conclusion: Treatment with QW epoetin-α was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic.     

Patient‐reported outcomes in a randomized trial comparing four different treatment strategies in recent‐onset rheumatoid arthritis

Objective

To investigate the effectiveness of 4 different treatment strategies for recent‐onset rheumatoid arthritis (RA) on 2‐year patient‐reported outcomes, including functioning and quality of life.

Methods

A total of 508 patients with recent‐onset RA were randomly assigned to 1) sequential monotherapy, 2) step‐up combination therapy, both starting with methotrexate, 3) initial combination therapy, including a tapered high‐dose prednisone, or 4) initial combination therapy with methotrexate and infliximab. Treatment was adjusted every 3 months if the Disease Activity Score (DAS) remained >2.4. The McMaster Toronto Arthritis Patient Preference Disability Questionnaire, the Short Form 36 (SF‐36), and scores for pain, global health, and disease activity measured on a 100‐mm visual analog scale (VAS) were compared between groups at baseline and every 3 months thereafter for 2 years.

Results

After 2 years, all patient‐reported outcomes had improved significantly from baseline, irrespective of the treatment strategy. SF‐36 subscale scores approached population norms for 3 physical components, and achieved population norms (P > 0.05) for bodily pain and 4 mental components. Improvement in functioning, VAS scores, and physical items of the SF‐36 occurred significantly earlier in patients treated with initial combination therapies (all comparisons after 3 months: overall P < 0.001; P < 0.05 for groups 1 and 2 versus groups 3 and 4).

Conclusion

All 4 DAS‐driven treatment strategies resulted in substantial improvements in functional ability, quality of life, and self‐assessed VAS scores after 2 years. Initial combination therapy led to significantly faster improvement in all patient‐reported measures.     

Factors associated with rapid and early virologic response to peginterferon alfa‐2a/ribavirin treatment in HCV genotype 1 patients representative of the general chronic hepatitis C population

Summary. Rapid virologic response (RVR) and complete early virologic response (cEVR) are associated with sustained virologic response to hepatitis C virus (HCV) therapy. We retrospectively examined baseline and on‐treatment factors associated with RVR (HCV RNA undetectable at week 4) and cEVR (HCV RNA undetectable at week 12, regardless of week 4 response). The analysis comprised 1550 HCV genotype‐1 patients from five clinical trials, including three enriched with difficult‐to‐treat populations, randomized to peginterferon alfa‐2a 180 μg/week plus ribavirin 1000–1200 mg/day. Overall, 15.6% achieved RVR and 54.0% achieved cEVR. Baseline factors predictive of RVR were serum HCV RNA ≤ 400 000 IU/mL (OR: 7.34; P < 0.0001), alanine aminotransferase >3 × ULN (OR: 2.01; P < 0.0001), non‐cirrhotic status (OR: 1.92; P = 0.0087), age ≤ 40 years (OR: 1.56; P = 0.0085), white non‐Latino ethnicity (OR: 1.41; P = 0.0666) and individual study (P < 0.0001). These factors plus body mass index ≤ 27 kg/m² were predictive of cEVR. After adjusting for these factors, mean on‐treatment ribavirin dose >13 mg/kg/day was predictive of RVR (OR: 1.69; P = 0.005) and cEVR (OR: 1.24; P = 0.09), whereas peginterferon alfa‐2a dose reduction was not. Greater decreases in haematologic parameters were observed in patients who achieved cEVR compared with patients who did not. In conclusion, several baseline and on‐treatment factors were associated with RVR and cEVR to peginterferon alfa‐2a plus ribavirin in difficult‐to‐treat HCV genotype‐1 patients, providing important prognostic information on the antiviral response in a patient cohort that is reflective of the general chronic hepatitis C population.     

A Retrospective Study on Erythropoiesis Stimulating Agent Dose Reducing Potential of an Anti‐Platelet Activation Membrane Dialyzer in Hemodialysis Patients

Our previous small‐scale trial demonstrated an erythropoiesis stimulating agent (ESA)‐sparing potential of the TORAYLIGHT NV (NV) dialyzer in hemodialysis patients with high interleukin‐6 levels. We now retrospectively explored this ESA‐sparing potential of the NV dialyzer in 122 and 129 prevalent dialysis patients who were on the NV and conventional polysulfone (PS) dialyzers, respectively, for 12 months. ESA resistance index (ERI) increased with the PS dialyzers whereas neither ERI nor ESA dose changed with the NV dialyzer. Analyses of baseline ERI or ESA dose‐based subgroups revealed a decrease in ERI and ESA dose with the NV dialyzer in patients with a baseline ERI ≥12 IU·dL/week·kg·g Hb (P < 0.05) and in those with a baseline ESA dose >6000 IU/week (P < 0.001), respectively. Neither ERI nor ESA dose improved in the corresponding subgroups on the PS dialyzers. These findings suggest that NV dialyzer can improve ESA responsiveness in hemodialysis patients with advanced ESA resistance.     

Hodgkin lymphoma post‐transplant lymphoproliferative disorder: A comparative analysis of clinical characteristics,prognosis, and survival

Hodgkin lymphoma post‐transplant lymphoproliferative disorder (HL‐PTLD) is an uncommon PTLD with unclear prognosis and differences between HL‐PTLD and immunocompetent HL are not well defined. Patient characteristics were compared among 192 patients with HL‐PTLD from the Scientific Registry of Transplant Recipients and 13,847 HL patients in SEER (HL‐SEER). Overall survival (OS) and disease‐specific survival (DSS) were compared after exact matching. Additionally, multivariable analyses were used to identify prognostic markers of survival and associations between treatment and survival. Median time from transplant to HL‐PTLD diagnosis was 88 months. When compared with HL‐SEER, patients with HL‐PTLD were older (median age, 52 vs. 36 years, P = 0.001), more likely male (73% vs. 54%, P < 0.001), Caucasian (81% vs. 70%, P = 0.02), and had extranodal disease (42% vs. 3%, P < 0.001). Five‐year OS for patients with HL‐PTLD was 57% versus 80% for HL‐SEER (P < 0.001); DSS was also inferior (P < 0.001). For patients with HL‐PTLD, the use of any chemotherapy was associated with decreased hazard of death (HR = 0.36, P < 0.001). Furthermore, patients who received no chemotherapy or nontraditional HL regimens had increased hazard of death (aHR = 2.94, P = 0.001 and 2.01, P = 0.04) versus HL‐specific chemotherapy regimens. In multivariable analysis, advanced age and elevated creatinine were associated with inferior OS (aHR = 1.26/decade P < 0.001 and 1.64/0.1 mg/dL increase P = 0.02). A prognostic score based on the number of these adverse factors (0, 1, 2) was associated with 10‐year OS rates of 79%, 53%, and 11%, respectively (P < 0.001). Altogether, HL‐PTLD patients have inferior survival when compared with HL‐SEER. Furthermore, treatment with HL‐specific chemotherapy was associated with improved OS, whereas age and creatinine identified patients with markedly divergent survival. Am. J. Hematol. 91:560–565, 2016. © 2016 Wiley Periodicals, Inc.     

Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high‐grade myelodysplastic syndromes

Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment‐related morbidity and mortality. Herein, we investigate how pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals receiving curative‐intent induction chemotherapy with cytarabine and an anthracycline (“7 + 3”; n = 175) or a “7 + 3”‐like regimen (n = 30). Among the entire cohort, baseline grade 4 neutropenia (i.e., absolute neutrophil count <500 cells/µL) was associated with development of fever (P = 0.04), documented infection (P < 0.0001), and bacteremia (P = 0.002) but not requirement for intensive care unit‐level care; after exclusion of the 30 patients who received “7 + 3”‐like induction, baseline grade 4 neutropenia remained associated with documented infection (P < 0.0001) and bacteremia (P = 0.0005). Among patients achieving a complete remission with the initial treatment cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery (P < 0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04–3.34; P=0.04)‐fold, 4.95 (2.20–11.16; P<0.001)‐fold, and 3.14 (0.99–9.98; P=0.05)‐fold higher in patients with initial grade 4 neutropenia. Together, our studies identify severe baseline neutropenia as a risk factor for infection‐associated adverse events after induction chemotherapy and may provide the rationale for the risk‐adapted testing of myeloid growth factor support in this high‐risk AML/MDS patient subset. Am. J. Hematol. 89:423–428, 2014. © 2014 Wiley Periodicals, Inc.     

Short‐term and long‐term effect of diaphragm biofeedback training in gastroesophageal reflux disease: an open‐label,pilot, randomized trial

This study investigated the effectiveness of diaphragm biofeedback training (DBT) for patients with gastroesophageal reflux disease (GERD). A total of 40 patients with GERD treated at the Peking Union Medical College Hospital between September 2004 and July 2006 were randomized to receive DBT and rabeprazole proton pump inhibitor (PPI) or rabeprazole alone. The DBT + rabeprazole group received DBT during the 8‐week initial treatment; the rabeprazole group did not. During the 6‐month follow up, all patients took acid suppression according to their reflux symptoms, and the patients in the DBT + rabeprazole group were required to continue DBT. The primary outcome (used for power analysis) was the amount of acid suppression used at 6 months. Secondary outcomes were reflux symptoms, health‐related quality of life (HRQL), and esophageal motility differences after the 8‐week treatment compared with baseline. Acid suppression usage significantly decreased in the DBT + rabeprazole group compared with the rabeprazole group at 6 months (P < 0.05). At 8 weeks, reflux s ymptoms and GERD‐HRQL were significantly improved in both groups (P < 0.05), without difference between them. Crural diaphragm tension (CDT) and gastroesophageal junction pressure (GEJP) significantly increased in the DBT + rabeprazole group (P < 0.05), but without change in lower esophageal sphincter (LES) pressure. There was no significant change in CDT, GEJP, and LES pressure compared with baseline in the rabeprazole group. In conclusion, long‐term DBT could reduce acid suppression usage by enhancing the anti‐reflux barrier, providing a non‐pharmacological maintenance therapy and reducing medical costs for patients with GERD.     

A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy‐associated anemia

Erythropoiesis‐stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy‐associated anemia (CAA). Extended‐interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly (“40K” arm), EA 80,000 U every 3 weeks (“80K”), EA 120,000 U every 3 weeks (“120K” arm), or DA 500 mcg every 3 weeks (“DA”), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient‐reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA‐approved schedules tested—weekly EA 40,000 U, and every 3 week DA 500 mcg—are reasonable standards for CAA therapy. Am. J. Hematol. 90:877–881, 2015. © 2015 Wiley Periodicals, Inc.     

Enzyme replacement therapy with taliglucerase alfa: 36‐month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase

Taliglucerase alfa is the first available plant cell‐expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB‐06‐002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB‐06‐002 who continued receiving taliglucerase alfa in extension Study PB‐06‐003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB‐06‐003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30–33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, ?1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), ?19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, ?51.5% (±8.1%; n = 10); and CCL18 concentration, ?36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment‐related adverse events were mild or moderate and transient. The 36‐month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661–665, 2016. © 2016 Wiley Periodicals, Inc.     

Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous Iron in patients with chemotherapy‐induced anemia

This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double‐blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL^?1, and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL^?1). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT‐F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan–Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

A Model Program of Community‐Based Supports for Older Adults at Risk of Nursing Facility Placement

Transitioning an older adult into a nursing facility is a major life event for older adults (care recipients, CRs) and their family caregivers (CGs). This article describes the implementation of a community living program and presents findings on important health and well‐being indicators. One hundred ninety‐one participants aged 60 and older not eligible for or currently enrolled in Medicaid and meeting four risk domains (functional, health, cognitive/emotional, informal support system) were enrolled for the 10‐month program. Two evidence‐based interventions were blended into a comprehensive community‐based approach to long‐term care that included $750 per month for home care services. Measures were conducted at baseline and 6 and 12 months. Nine (6%) participants did not complete the program because of nursing facility admission. CRs had fewer physician visits (4.1 vs 7.3, P < .001), emergency department visits (0.3 vs 1.4, P < .001), hospital stays (0.4 vs 0.9, P < .001), and total nights in the hospital (0.8 vs 5.1, P < .001) at 12 months than at baseline. Center for Epidemiologic Studies Depression Scale (CES‐D) scores also improved significantly (6.8 vs 9.4, P < .001). CGs had improvements in CES‐D scores (5.9 vs 3.9, P < .001) and CG burden (14.7 s 12.6, P = .01) from baseline to 12 months. This multicomponent program improved the physical and mental health of CGs and CRs at risk of nursing facility placement. Future studies are needed to compare the overall placement rate to determine the success of diverting nursing facility placement in this population of older adults.