Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

Breathlessness, Functional Status, Distress and Palliative Care Needs Over Time in Patients With Advanced Chronic Obstructive Pulmonary Disease or Lung Cancer:A Cohort Study

Context. Breathlessness is a distressing symptom in advanced disease. Understanding its patterns, burden, and palliative care (PC) needs over time is important to improve patients' quality of life. Objectives. To describe and compare the courses of refractory breathlessness, functional status, distress, and PC needs in patients with advanced chronic obstructive pulmonary disease (COPD) or lung cancer (LC) over time. Methods. This was a cohort study of patients with COPD (Stage III/IV) or LC. Data were assessed monthly with up to 12 telephone interviews, using the modified Borg Scale, Karnofsky Performance Status Scale, Distress Thermometer, and Palliative care Outcome Scale as outcomes measures. Descriptive analysis compared all outcomes between COPD and LC at baseline and over time (forward from study entry and backward from death). Results. A total of 82 patients (50 COPD and 32 LC), mean (SD) age of 67.2 (7.8), and 36% female were included (8 COPD and 23 LC deceased). The patients with COPD perceived higher levels of breathlessness and distress at lower functional status steadily over time. The LC patients' breathlessness, distress, and PC needs increased, whereas functional status decreased toward death. The PC needs were similar between disease groups. Breathlessness was negatively correlated with functional status (COPD = mean r = -0.20, P = 0.012; LC = mean r = -0.277, P = 0.029) and positively correlated with PC needs in COPD patients (mean r = 0.343, P < 0.001). Death was significantly predicted by diagnosis (LC: hazard ratio = 7.84, P < 0.001) and functional status (10% decline: hazard ratio = 1.52, P = 0.001). Conclusion. The PC needs of patients with advanced COPD are comparable with LC patients, and breathlessness severity and distress are even higher. The care for COPD patients requires further improvement to address symptom burden and PC needs. (C) 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved

Characteristics of episodic breathlessness as reported by patients with advanced chronic obstructive pulmonary disease and lung cancer:Results of a descriptive cohort study

Background: Episodic breathlessness is one form of refractory breathlessness. Better understanding of the symptom is necessary for effective management. Aim: The aim was to describe the characteristics of episodic breathlessness in patients with advanced chronic obstructive pulmonary disease or lung cancer. Design: This is a longitudinal cohort study. Outcomes were assessed monthly by up to 13 telephone interviews: peak severity (modified Borg scale: 0–10), duration, frequency, and timing of breathlessness episodes. Data from each episode were pooled and analyzed using descriptive statistics. Associations between outcomes were explored by correlation coefficients. Setting/participants: Patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease classification stage III or IV) or primary lung cancer (any stage) were recruited in two inpatient units (internal medicine) and two outpatient clinics in Oldenburg, Germany. Results: A total of 82 patients (50 chronic obstructive pulmonary disease, 32 lung cancer), mean age (standard deviation) 67 years (8 years) and 36% female, were included reporting on 592 breathlessness episodes (chronic obstructive pulmonary disease: 403, lung cancer: 189). Peak severity was perceived significantly higher in chronic obstructive pulmonary disease patients than in lung cancer patients (mean (standard deviation) Borg scale: 6.2 (2.1) vs 4.2 (1.9); p < 0.001). Episodes described by chronic obstructive pulmonary disease patients were longer than those described by lung cancer patients (median (range): 7 min (0–600) vs 5 min (0.3–120), p = 0.002)). Frequency was similar and most often daily in both groups. Severity and frequency of episodes were correlated in lung cancer patients (r = 0.324, p = 0.009). Conclusion: Most breathlessness episodes are short (minutes) and severe with significant differences between chronic obstructive pulmonary disease and lung cancer patients. Effective management strategies are warranted to improve symptom relief and coping