Cornec, Divi

ObjectiveTo estimate the annual incidence, prevalence, and mortality of antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV) and its subsets, granulomatosis with polyangiitis (Wegener's) (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), in a US‐based adult population.MethodsAll medical records of patients with a diagnosis of, or suspicion of having, AAV in Olmsted County, Minnesota from January 1, 1996 to December 31, 2015 were reviewed. AAV incidence rates were age‐ and sex‐adjusted to the 2010 US white population. Age‐ and sex‐adjusted prevalence of AAV was calculated on January 1, 2015. Survival rates observed in the study cohort were compared with expected rates in the Minnesota population.ResultsOf the 58 incident cases of AAV in Olmsted County during the study period, 23 (40%) were cases of GPA, 28 (48%) were cases of MPA, and 7 (12%) were cases of EGPA. Overall, 28 (48%) of the patients with AAV were women and 57 (98%) were white. The mean ± SD age at diagnosis was 61.1 ± 16.5 years. Thirty‐four patients (61%) had myeloperoxidase (MPO)–ANCAs, and 17 (30%) were positive for proteinase 3 (PR3)–ANCAs; 5 (9%) were ANCA‐negative. The annual incidence of AAV was 3.3 per 100,000 population (95% confidence interval [95% CI] 2.4–4.1). The incidence rates of GPA, MPA, and EGPA were 1.3 (95% CI 0.8–1.8), 1.6 (95% CI 1.0–2.2), and 0.4 (95% CI 0.1–0.6), respectively. The overall prevalence of AAV was 42.1 per 100,000 (95% CI 29.6–54.6). The mortality rate among AAV patients overall, and among patients with EGPA, those with MPA, and those with MPO‐ANCAs, was increased in comparison to the Minnesota general population (each P < 0.05), whereas mortality rates among patients with GPA, those with PR3‐ANCAs, and ANCA‐negative patients did not differ from that in the general population.ConclusionThe annual incidence of AAV in Olmsted County, Minnesota over the 20 years of the study was 3.3 per 100,000, with a prevalence of 42.1 per 100,000, which is substantially higher than the rates reported in other areas worldwide. The incidence of GPA was similar to that of MPA. Patients with MPA and those with EGPA, but not patients with GPA, experienced higher rates of mortality than that in the Minnesota general population. MPO‐ANCAs were a marker of poor survival in this population of patients with AAV.

ObjectiveTo report the point prevalence of primary Sjögren's syndrome (SS) in the first US population‐based study.MethodsCases of all potential primary SS patients living in Olmsted County, Minnesota, on January 1, 2015, were retrieved using Rochester Epidemiology Project resources, and ascertained by manual medical records review. Primary SS cases were defined according to physician diagnosis. The use of diagnostic tests was assessed and the performance of classification criteria was evaluated. The number of prevalent cases in 2015 was also projected based on 1976–2005 incidence data from the same source population.ResultsA total of 106 patients with primary SS were included in the study: 86% were female, with a mean ± SD age of 64.6 ± 15.2 years, and a mean ± SD disease duration of 10.5 ± 8.4 years. A majority were anti‐SSA positive (75%) and/or anti‐SSB positive (58%), but only 22% met American–European Consensus Group or American College of Rheumatology criteria, because the other tests required for disease classification (ocular dryness objective assessment, salivary gland functional or morphologic tests, or salivary gland biopsy) were rarely performed in clinical practice. According to the physician diagnosis, the age‐ and sex‐adjusted prevalence of primary SS was 10.3 per 10,000 inhabitants, but according to classification criteria, this prevalence was only 2.2 per 10,000. The analysis based on previous incidence data projected a similar 2015 prevalence rate of 11.0 per 10,000.ConclusionThe prevalence of primary SS in this geographically well‐defined population was estimated to be between 2 and 10 per 10,000 inhabitants. Physicians rarely used tests included in the classification criteria to diagnose the disease in this community setting.

Abstract The prognosis of the antineutrophil cytoplasmic antibody associated vasculitides (AAV), microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA), has been fundamentally improved over the last five decades by the use of glucocorticoids and immunosuppressants, turning them from consistently fatal diseases into chronic conditions. The long-term course is now largely determined by the frequency of disease flares and by accruing damage caused by disease activity and treatment-related comorbidities. This review summarizes the evidence derived from clinical trials performed during the last 30 years and the remaining clinical unmet needs that new studies aim to address. In MPA and GPA, ongoing studies assess (i) different strategies to reduce cumulative glucocorticoid doses currently used for induction and maintenance of remission, (ii) the efficacy of new drugs and (iii) the optimal duration of immunosuppression and the use of biomarkers to individualize therapy. Prospective randomized trials also target disease-associated cardiovascular risk and infections. The first prospective controlled trials specifically designed for EGPA have recently been launched and could lead to new therapeutic options for patients diagnosed with this rare disease. This is an exciting time for researchers in the field of AAV, and for patients as collaborative efforts raise the hope of developing new therapies and more individualized approaches to the management of the diseases, maximizing efficacy while minimizing treatment toxicities.

Abstract Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring (TDM) without relying on mAb specific reagents will be needed. In this study we demonstrate that liquid-chromatography?mass spectrometry (LC?MS) can be used to perform TDM of mAbs in the same manner as smaller nonbiologic drugs. The assay uses commercially available reagents combined with heavy and light chain disulfide bond reduction followed by light chain analysis by microflow-LC?electrospray ionization-quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF MS). Quantification is performed using the peak areas from multiply charged mAb light chain ions using an in-house developed software package developed for TDM of mAbs. The data presented here demonstrate the ability of an LC?MS assay to quantify a therapeutic mAb in a large cohort of patients in a clinical trial. The ability to quantify any mAb in serum via the reduced light chain without the need for reagents specific for each mAb demonstrates the unique capabilities of LC?MS. This fact, coupled with the ability to phenotype a patient?s polyclonal repertoire in the same analysis further shows the potential of this approach to mAb analysis.