Showing papers by "Aladdin J Mohammad published in 2020"

An update on the epidemiology of ANCA-associated vasculitis

Abstract: ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Epidemiological studies in AAV are important in understanding possible aetiologic mechanisms and facilitating healthcare planning. However, epidemiological studies present a number of challenges including clear definition of cases differentiated from other clinical disorders, and identification of cases due to the rarity of AAV. The aim of this review is to summarize different aspects on the epidemiology of ANCA-associated vasculitis from different geographical areas throughout the world. During the past three decades, development of classification criteria worldwide, including the ACR classification of 1990, the Chapel Hill consensus definitions updated in 2012 and the EMA algorithm has facilitated epidemiology studies in AAV. The available epidemiological studies reported in AAV suggest that incidence and prevalence may have increased over the past 30 years. Possible explanations for this increase may be a genuine increase in incidence, the evolution of classification criteria and the definition, and availability and wider use of ANCA serology to aid diagnosis, and greater physician awareness through education. The age-specific incidence for the whole group of AAV showed a clear increase with age. However, there has been a clear shift in the peak age at onset towards a higher age during the last 20-30 years. In addition, variation in incidence of AAV between men and women has been clearly evident in a number of epidemiological studies.

International consensus on antineutrophil cytoplasm antibodies testing in eosinophilic granulomatosis with polyangiitis

Abstract: An international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented ANCA, specific for myeloperoxidase (MPO), can be detected in 30-35% of EGPA patients MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms, purpura, polyneuropathy, unexplained heart, gastrointestinal or kidney disease, and/or pulmonary infiltrates or hemorrhage A positive MPO-ANCA result contributes to the diagnostic work‑up for EGPA Patients with MPO-ANCA associated EGPA have more frequently vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations than patients with ANCA negative EGPA However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having "vasculitic" or "eosinophilic" EGPA At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab or mepolizumab should be added to conventional glucocorticoid treatment In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset

Negative associations for fasting blood glucose, cholesterol and triglyceride levels with the development of giant cell arteritis.

Abstract: Objectives. To investigate metabolic features that may predispose to GCA in a nested case-control study. Methods. Individuals who developed GCA after inclusion in a population-based health survey (the Malmo Preventive Medicine Project; N ¼ 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database. Results. A total of 76 cases with a confirmed incident diagnosis of GCA (61% female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0-32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (S.D. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (S.D. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (S.D. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides]. Conclusion. Development of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA. (Less)

Malignancies in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis: A Population-based Cohort Study.

Abstract: Objective Patients with ANCA-associated vasculitides (AAV) exhibit higher rates of malignancy than the general population. In this study, we assessed whether the cancer risk is increased in a well-characterized population-based cohort of AAV in southern Sweden, followed for a median time of 8 years. Methods With case record review, the outcomes and malignancy development in a cohort of 195 patients with AAV (granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), diagnosed between 1997 and 2010, were assessed. The patients were followed until death or December 31, 2015. The age- and sex-standardized incidence ratios (SIR) were estimated using the Swedish population data as a reference. Results During the approximately 1500 person-years observation period, we found 60 cancers in 52 of the 195 patients. SIR (95% CI) was 2.8 (2.1-3.6) for cancers at all sites, 1.8 (1.3-2.5) for all cancers excluding squamous cell carcinoma (SCC), 12.9 (8.4 -18.8) for SCC, 4.3 (1.4-10.0) for bladder cancer, and 7.0 (1.4-20.5) for pancreatic cancer. Cumulative doses of cyclophosphamide (CYC) less than 10g were not associated with higher incidence of cancers other than SCC (SIR 1.63 (95% CI: 0.8-2.9). Conclusion In contrast to recent publications assessing malignancy risk in patients with AAV, we show in this population-based cohort of patients, a persistent increased risk for overall malignancy, bladder cancer, and pancreatic cancer as well as a markedly increased risk for SCC. There was no increase in incidence of cancers other than SCC for those treated with less than 10 grams CYC.

Malignancies In Giant Cell Arteritis: A Population-Based Cohort Study

Abstract: Objective To investigate the risk of cancer in patients with biopsy-proven giant cell arteritis (GCA) from a defined population in southern Sweden. Methods The study cohort consisted of 830 patients (mean age at GCA diagnosis was 76.3 years, 74 % women) diagnosed with biopsy-proven GCA between 1997 and 2010. Temporal artery biopsy results were retrieved from a regional database and reviewed to ascertain GCA diagnosis. The cohort was linked to the Swedish Cancer Registry. The patients were followed from GCA diagnosis until death or December 31, 2013. Incident malignancies registered after GCA diagnosis were studied. Based on data on the first malignancy in each organ system, age- and sex standardized incidence ratios (SIR) with 95 % confidence intervals (CI) were calculated compared to the background population. Results 107 patients (13%) were diagnosed with a total of 118 new malignancies after the onset of GCA. The overall risk for cancer after the GCA diagnosis was not increased (SIR 0.98; 95% CI 0.81 – 1.17). However, there was an increased risk for myeloid leukemia (2.31; 95% CI 1.06 – 4.39) and a reduced risk for breast cancer (0.33; 95% CI 0.12 – 0.72) and upper gastrointestinal tract cancer (0.16; 95% 0.004- 0.91). Rates of other site-specific cancers were not different from expected. Conclusion In this Swedish population-based cohort of GCA, the overall risk for cancer was not increased compared to the background population. However, there was an increased risk for leukemia and a decreased risk for breast and upper gastrointestinal tract cancer.

Effect of Treatment on Damage and Hospitalization in Elderly Patients with Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

Abstract: Objective Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. Methods Consecutive patients from Sweden, England, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide, rituximab, and corticosteroids the first three months was registered. Outcomes up to two years from diagnosis included vasculitis damage index (VDI), hospitalization, and cause of death. Results Treatment data was available for 167 of 202 patients. At two years, 4% had no items of damage. There was a positive association between VDI score at two years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using cyclophosphamide or rituximab. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. MPO-ANCA positivity and lower creatinine levels decreased the odds for readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. Conclusion Immunosuppressive treatment with cyclophosphamide or rituximab in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first three months was associated with treatment-related damage and fatal infections.

Cardiovascular drug treatment, statins and biopsy-confirmed giant cell arteritis: a population-based case–control study

Abstract: Objective To determine whether exposure to cardiovascular medications and statins is associated with increased risk of giant cell arteritis (GCA). Design The population-based case–control study comprised a cohort of patients with biopsy-confirmed GCA linked to the Swedish Prescribed Drug Register to identify all exposure to drugs prior to diagnosis of GCA. Ten controls per GCA case, matched for age, sex and residential area, were included. Using corresponding Anatomical Therapeutic Chemical codes, ACE inhibitors, angiotensin II receptor blockers, beta-blocking agents, calcium antagonists, diuretics, statins and cardiac therapy drugs were investigated from July 1, 2005 to the diagnosis/index date. A conditional logistic regression model was fitted adjusted for income, education level and marital status. We repeated the analyses including only new drug users excluding those with any prescription during the year from July 1, 2005 to July 1, 2006. Results 574 cases (29% men) of diagnosed GCA and 5740 controls (29% men) were included. The mean age at diagnosis is 75 years (SD 8). Of the GCA cases, 71% had at least one dispensation of a cardiovascular drug prior to the index date, compared to 74% of controls. The ORs for the association of target drug exposure with GCA were Conclusion Statins may be associated with lower risk of incident biopsy-confirmed GCA. No association was evident for other studied drugs.

Op0148 mepolizumab for eosinophilic granulomatosis with polyangiitis (egpa): a retrospective real-world european study on 142 patients

Abstract: Background: Evidence on the efficacy of Mepolizumab (MEPO) in Eosinophilic Granulomatosis with Polyangiitis (EGPA) is scarce [1]. Objectives: To assess the efficacy and safety of MEPO in real-life clinical practice. Methods: We retrospectively included patients diagnosed with EGPA and treated with MEPO (100 or 300 mg/month). MEPO efficacy was evaluated in the first 12 months in terms of systemic disease and asthma control. The occurrence of any adverse event (AE) was recorded. Results: 142 patients were included (38% males; median age 46.4 (IQR 36.7-54.4); 110 and 32 on MEPO 100 and 300 mg/month, respectively). General, ear-nose-throat, pulmonary, and neurological symptoms significantly decreased during treatment (table 1). MEPO accounted for a significant reduction in the BVAS (figure 1) and for a steroid sparing effect (figure 2). The proportion of patients with asthma attacks decreased by 90% at 12 months compared to t0, and asthma-related emergency accesses dropped from 17.4% to 2.3%. Overall, 21.1% of patients had a non-serious AE. Conclusion: MEPO effectively controlled systemic and respiratory EGPA symptoms in a large European cohort, with no major safety concerns. References: [1]Wechsler et al. MEPO or Placebo for Eosinophilic Granulomatosis with Polyangiitis. NEJM. 2017 Disclosure of Interests: Alessandra Bettiol: None declared, Maria Letizia Urban: None declared, Federico Alberici: None declared, Carlo Agostini: None declared, Chiara Baldini: None declared, Enrica Bozzolo: None declared, Paolo Cameli: None declared, Nunzio Crimi: None declared, Stefano Del Giacco: None declared, Allyson Egan: None declared, Georgina Espigol-Frigole Consultant of: Roche and Janssen, Mara Felicetti: None declared, Marco Folci: None declared, Paolo Fraticelli: None declared, Marcello Govoni: None declared, Anna Kernder Grant/research support from: Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Carlo Lombardi: None declared, Giuseppe Lopalco: None declared, Claudio Lunardi: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Frank Moosig: None declared, Simone Negrini: None declared, Thomas Neumann: None declared, Pavel Novikov Grant/research support from: This work was supported by the 5-100 Project, Sechenov University, Moscow, Giuseppe Paolazzi: None declared, paola parronchi: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Vito Racanelli: None declared, Carlo Salvarani: None declared, Maxime Samson: None declared, Jan Schroeder: None declared, Savino Sciascia: None declared, Renato A. Sinico: None declared, Benjamin Terrier: None declared, Paola Toniati: None declared, Domenico Prisco: None declared, Augusto Vaglio: None declared, Giacomo Emmi: None declared