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

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Fertility preservation in women with vasculitis: experiences from the FertiPROTEKT network

Fertility preservation is not only important for malignant diseases but should also be offered to patients with autoimmune diseases (AID) like vasculitides, prior to cyclophosphamide therapy. No recommendations are available for patients with AID

Sexual dysfunction and depression in Behçet’s disease in comparison to healthy controls

Behçet's disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients' origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women's group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population

Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma--evaluation by using antimüllerian hormone and retrieved oocytes

To study whether the ovarian reserve in female lymphoma patients is already reduced before the start of chemotherapy

Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients

OBJECTIVE Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. METHODS The data of 3248 patients with SSc were analyzed. RESULTS Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. CONCLUSION These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed

Association of the ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire with established outcome measures in AAV

Objectives The ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire was developed to capture the impact of AAV and its treatment. We investigated the association of specific AAV-PRO domains with disease activity and extent, damage, depression, health-related quality of life and treatment. Methods In a prospective longitudinal study AAV-PRO, Beck’s depression inventory (BDI), Short Form 36 (SF36), BVAS and Vasculitis Damage Index (VDI) were completed at baseline (t1) and after 3–6 months (t2). In addition, patient data including diagnosis, therapies, relapses, and organ manifestations were recorded. Data were analyzed by t-tests and correlation-based regression analyses. Results 156 patients with AAV participated. The mean BVAS at the time of enrolment was 1.4 ± 3.74. Median AAV-PRO domain scores were higher in patients reporting “active disease” compared with patients reporting “in remission” (p< 0.001). In the correlation analyses all AAV-PRO domain scores correlated strongly with the BDI (all r ≥ 0.319, all p≤ 0.001) as well as all eight SF36 subdomains (all |r|≥0.267, all p≤ 0.001). The regression analyses showed that AAV-PRO domains were strongly predicted by BDI and SF36 domains (|β|≥0.240 for the strongest predictor of each domain). In the longitudinal comparison (t1/t2) there were no significant changes of the overall results. Conclusion Our data show convergent validity of all AAV-PRO subdomains with the established questionnaires BDI and SF-36. The AAV-PRO domains scores were not correlated with clinician derived instruments including the BVAS and VDI. Thus, we regard the AAV-PRO as a valuable addition that might complement traditional endpoints in clinical trials