Limited versus severe Wegener's granulomatosis: Baseline data on patients in the Wegener's granulomatosis etanercept trial

Abstract

Objective. To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease.Methods. Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected.Results. Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease.Conclusion. There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.

Clinical features and long‐term outcomes of 105 granulomatosis with polyangiitis patients: A single center experience from north India

“…4,7,8 Americans had a slightly higher lung involvement (75-85%) than both Indians and the Europeans. 5,6 Ocular manifestations were noted in 41% of patients in our study which was similar to that noted in previous studies. [4][5][6][7][8][9] Compared to the European population, fewer Indian and American patients had peripheral nervous system involvement.…”

“…Indian patients seem to have a slightly lower frequency of upper airway involvement, as only 79% of patients in our study and 80% of patients in the study by Kumar et al had ear, nose and throat manifestations compared to 90-98% among European and American patients. [4][5][6][7][8][9] Lung involvement was seen in 68% of our patients which was similar to that noted in European populations. 4,7,8 Americans had a slightly higher lung involvement (75-85%) than both Indians and the Europeans.…”

“…[11][12][13]15 ANCA was negative in 10% of patients in our study, which is similar to that reported from other studies, where ANCA negativity ranged from 10 to 13%. [4][5][6][7][8] Renal involvement was seen in fewer patients in our study population compared to studies from Europe, America and also older studies from India. The more recent Indian study by Kumar et al has also shown that renal involvement is seen in 33% of patients in their cohort.…”

“…GPA seems to affect a relatively younger population in India compared to European and American populations, as the mean age of presentation in our subjects is 40 years which is about a decade earlier than in European and American populations. [4][5][6][7][8] Older Indian studies have noted the mean age of presentation to be between 32 to 42 years, but a recent study documented a mean age of 46 years, which is comparable to that of Western studies. [11][12][13]15 ANCA was negative in 10% of patients in our study, which is similar to that reported from other studies, where ANCA negativity ranged from 10 to 13%.…”

“…2,3 Several large case series regarding GPA patients were published from various countries, with the largest series describing 445 GPA patients from Germany. [4][5][6][7][8] The first report of GPA from India was published in 1985 by Kumar et al followed by descriptions of 11 patients by Bambery et al in 1987. 9,10 Since then various case series have been published from India with the largest series of 45 patients being described by Kumar et al [11][12][13] In the present study, we describe the clinical features, organ involvement, histopathology findings, treatment and outcomes of 105 GPA patients treated at our center, a tertiary care hospital in India.…”