Benralizumab for eosinophilic granulomatosis with polyangiitis: a retrospective, multicentre, cohort study.

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.

Rapid onset of effect of benralizumab on respiratory symptoms in a patient with eosinophilic granulomatosis with polyangiitis.

A 63 years - old woman affected by severe eosinophilic asthma associated with EGPA presented refractory respiratory symptoms, resistant to high dose oral corticosteroid treatment. A significant hyper-eosinophilia was present at the blood test, and the ACT score was steadily low, despite the maximal dose of inhalation therapy. The CT chest scan showed a persistent diffuse bronchial wall thickening, pulmonary infiltration and paranasal sinusitis. We report here the rapid onset of effect of benralizumab 30 mg in a monthly subcutaneous injection in reducing patient's symptom, inducing regression of CT scan abnormalities, determining a steroid sparing effect and improving lung function tests after 3 months of therapy. A fast and stable reduction of peripheral eosinophilia associated with an increase in ACT score were also documented after the first dose of benralizumab.

Idiopathic Pulmonary Fibrosis (IPF) incidence and prevalence in Italy.

BACKGROUND: Studies of Idiopathic Pulmonary Fibrosis (IPF) epidemiology show regional variations of incidence and prevalence; no epidemiological studies have been carried out in Italy. OBJECTIVE: To determine incidence and prevalence rates of IPF in the population of a large Italian region. METHODS: in this cross-sectional study study data were collected on all patients of 18 years of age and older admitted as primary or secondary idiopathic fibrosing alveolitis (ICD9-CM 516.3) to Lazio hospitals, from 1/1/2005 to 31/12/2009, using regional hospital discharge, population and cause of death databases. Reporting accuracy was assessed on a random sample of hospital charts carrying the ICD9-CM 516.3, 516.8, 516.9 and 515 codes, by reviewing radiology and pathology findings to define cases as IPF "confident", "possible" or "inconsistent". RESULTS: Annual prevalence and incidence of IPF were estimated at 25.6 per 100,000 and 7.5 per 100,000 using the ICD9-CM code 516.3 without chart audit while they were estimated at 31.6 per 100,000 and at 9,3 per 100,000 for the IPF "confident" definition after hospital chart audit. CONCLUSION: The data provide a first estimate of IPF incidence in Italy and indicate that incidence and prevalence in southern European regions may be similar to those observed in northern Europe and North America.

A survey of credentialing practices of gastrointestinal endoscopy centers in the United States.

BACKGROUND: Competence in gastrointestinal (GI) endoscopy correlates with the number of procedures performed by the endoscopist. For each GI endoscopic procedure, the American Society for Gastrointestinal Endoscopy (ASGE) guidelines recommend minimum numbers needed to assess competence. METHODS: We conducted an anonymous mail survey to determine whether GI endoscopy centers in the United States follow ASGE or other guidelines for granting and renewing endoscopic privileges. RESULTS: Completed surveys were received from 479 respondents in 46 states, Puerto Rico, and the District of Columbia. Most respondents were either the physician director (24%) or nurse manager (57%) of the endoscopy center. Most centers have more than 5 endoscopists (62%), and gastroenterologists performed procedures in the majority of the centers (89%). For initial endoscopic credentialing, few centers require a minimum number of procedures and only 10% meet ASGE criteria. To maintain credentials, less than one third require a minimum number and only 2% require more than 25 procedures/year. Although three fourths report periodic review of procedures, less than 5% review them more frequently than every 6 months. Only 20% of centers had ever denied endoscopic privileges (poor skills [80%], no references [27%], poor communication [7%], and excess complications [6%]) for which half faced litigation. CONCLUSIONS: Most GI endoscopy centers responding to this survey have no minimum standards for determining endoscopic competence and may credential GI endoscopists with suboptimal training. Only 10% adhere to ASGE guidelines. Moreover, there is lack of uniformity to application of these guidelines, and few centers use resulting data to deny or renew credentials. To guarantee high-quality endoscopic practice, more stringent, universal credentialing standards are required.

Hepatitis C knowledge among primary care residents: is our teaching adequate for the times?

BACKGROUND: Increasingly, primary care (PC) physicians will be the first to encounter patients with hepatitis C virus (HCV) infection. AIM: To determine opinions and practices of PC residents regarding HCV. METHODS: We administered a one-page questionnaire to 180 PC residents at five U.S. training programs. RESULTS: Respondents were distributed equally across postgraduate year, 83% were U.S. graduates, and 44% had seen >11 (HCV) patients in the past year. Residents tested for HCV in persons with: increased transaminases (83%), history of blood transfusion (46%), multiple tattoos (57%), +ANCA (16%), and alcohol abuse (31%). Sixteen percent of respondents tested all patients. Forty-one percent would vaccinate HCV patients for hepatitis A and 65% for hepatitis B while only 19% and 78% knew the respective vaccination schedules. Although no vaccine is available, 66% recommended vaccination for HCV. Only 37% and 29%, respectively, reported HCV genotype 1 as most common and most resistant to treatment. Fifty-three percent recommend liver biopsy before treating HCV. Only 52% reported alpha-interferon (IFN) with ribavirin as initial treatment for HCV while 28% recommend ribavirin or lamivudine alone or combinations of IFN and lamivudine or amantadine. As contraindications to treatment, 33% reported AIDS with PCP infection, 19% coronary artery disease, and 19% suicidal ideation. Sixty-nine percent felt that there was insufficient information on HCV. CONCLUSIONS: Many PC residents lack adequate knowledge of recommended guidelines for the management of HCV. Many test for HCV in inappropriate situations, are unclear regarding available vaccines and their administration, and are uncertain about current treatment. Education of PC residents on guidelines for detection and management of HCV must be improved.