Carbon nanotube (CNT) reinforced (0.05–0.5% by wt) polycaprolactone (PCL)‐based composites were prepared by compression molding. Addition of 0.2% CNT caused a 131% improvement of tensile strength (TS) of PCL films. The tensile modulus (TM) and elongation at break (Eb) of PCL were also significantly improved with the addition of CNT. The water vapor permeability of PCL was 1.51 g·mm/m2·day but 0.2% CNT containing PCL films showed 1.08 g·mm/m2·day. Similarly, the oxygen transmission rate (OTR) of PCL films was found to decrease with the addition of CNT. But, carbon dioxide transmission rate (CO2TR) of PCL film was improved due to incorporation of CNT. Effect of gamma radiation on PCL films and CNT reinforced PCL‐based composites were also studied. The TS of the irradiated (10 kGy) PCL films gained to 75% higher than control sample. The TS of the 0.2% CNT reinforced composite film was reached to 41 MPa at 15 kGy dose. The barrier properties of non‐irradiated and irradiated (10 kGy) PCL films and composites (0.2% CNT reinforced) were also measured. Both PCL films and composites showed lower values of WVP upon irradiation and indicated better water vapor barrier. The OTR and CO2TR of the irradiated (10 kGy) PCL films and composites were decreased compared to their counterparts. Surface and interface morphologies of the composites were studied by scanning electron microscopy. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013

BACKGROUND Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

Background Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. Methods In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed. Results A total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had ≥ 24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was 1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies. Conclusions In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889.)

Background The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is unknown. Methods In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months. Results A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide–azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P = 0.01) and at 12 months (P = 0.009) but not at 18 months (P = 0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events. Conclusions In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, NCT00104299.)