INTRODUCTIONFunctional, or non-ulcer, dyspepsia is a common gastrointestinal disorder characterized by upper abdominal pain or discomfort in the absence of identi®able organic aetiologies. 1 A review of oesophagogastroduodenoscopy results found that ulcers, re¯ux oesophagitis and cancer account for diagnoses in less than half of patients with dyspepsia-like symptoms. 2 Functional dyspepsia is therefore considered to be the underlying cause of the majority (50±60%) of dyspepsia-like symptoms that occur in the general population. 2±4 Functional dyspepsia is usually a life-long, recurring condition that impacts quality of life and contributes signi®cantly to healthcare expenses. Functional dyspepsia accounts for a signi®cant number of gastrointestinal consultations from primary care providers, and is a common diagnosis in gastroenterology practices. 4, 5 A signi®cant percentage of overall costs associated with functional dyspepsia appear to be due to an increased use Results: Twelve-week average rates of adequate relief of pain or discomfort were 46% (95% CI: 37±54%) 2 , 55%
The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome.A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 ± 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear–nose–throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 ± 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.
IntroductionThe purpose of this observational study was to analyze the rates, characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases (SAD) who were treated off-label with biological agents in daily practice.MethodsThe BIOGEAS registry is an ongoing Spanish prospective cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe, refractory SAD. Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death. Patients contributed person-years of follow-up for the period in which they were treated with biological agents.ResultsA total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010. The first biological therapies included rituximab in 264 (77%) patients, infliximab in 37 (11%), etanercept in 21 (6%), adalimumab in 19 (5%), and 'other' agents in 3 (1%). Forty-five severe infections occurred in 37 patients after a mean follow-up of 26.76 months. These infections resulted in four deaths. The crude rate of severe infections was 90.9 events/1000 person-years (112.5 for rituximab, 76.9 for infliximab, 66.9 for adalimumab and 30.5 for etanercept respectively). In patients treated with more than two courses of rituximab, the crude rate of severe infection was 226.4 events/1000 person-years. A pathogen was identified in 24 (53%) severe infections. The most common sites of severe infection were the lower respiratory tract (39%), bacteremia/sepsis (20%) and the urinary tract (16%). There were no significant differences relating to gender, SAD, agent, other previous therapies, number of previous immunosuppressive agents received or other therapies administered concomitantly. Cox regression analysis showed that age (P = 0.015) was independently associated with an increased risk of severe infection. Survival curves showed a lower survival rate in patients with severe infections (log-rank and Breslow tests < 0.001).ConclusionsThe rates of severe infections in SAD patients with severe, refractory disease treated depended on the biological agent used, with the highest rates being observed for rituximab and the lowest for etanercept. The rate of infection was especially high in patients receiving three or more courses of rituximab. In patients with severe infections, survival was significantly reduced. Older age was the only significant predictive factor of severe infection.
Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.
Objectives To analyze the efficacy and safety of treatment with belimumab, a monoclonal antibody that specifically binds the soluble form of the protein human B lymphocyte stimulator B (BLyS), in SLE patients refractory to standard treatment. Methods In 2006, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the BIOGEAS registry, a multicenter study recruiting patients with refractory systemic autoimmune diseases treated with biological agents. Results On December 31, 2013, a total of 10 patients treated with belimumab were included in the BIOGEAS Registry, 9 females and 1 male, with a mean age of 41.8 years (range 24-71 years). These patients were heavily treated, with a mean of 7 years of corticosteroid treatment, antimalarials and at least one immunosuppressive agent, mycophenolate in 9, azathioprine in 7, metothrexate in 4, cyclosphosphamide in 2, cyclosporine A in 2, tacrolimus in 2 and talidomide in 2. Belimumab (10mg/kg) was administered in combination with corticosteroids (in all patients), antimalarials (6 patients) and immunosuppressive agents (8 patients, 6 with mycophenolate). The baseline average activity score (SELENA-SLEDAI) was 12 (range 6-33); 8 patients had high titers of anti-dsDNA and/or hypocomplementemia. Therapeutic indication included refractory mucocutaneous involvement (4 patients), refractory vasculitis (3 patients), systemic disease (2 patients) and refractory lupus nephritis (1 patient). After a mean follow-up of 7 months (range 2-12), clinical response could be evaluated in 9 patients, 8 classified as responders (improvement greater than 80% in 5 patients), while the remaining patient was classified as stable. Two patients (20%) developed adverse events (raised transaminases and systemic cryptococcosis due to severe CD4 lymphopenia); there were no deaths or lupus flares. Conclusions These postmarketing data in Spanish SLE patients in whom belimumab was used following the recommendations approved by the FDA/EMA (refractory disease to standard treatment, clinical and immunological active disease, SELENA-SLEDAI>6) have showed promising results, with a good therapeutic response and a safety profile similar to other biological therapies used off-label in patients with SLE. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5447
Background and objectives There is only one biologic agent approved for use in SLE, but some are used off-label in various settings. To obtain information systematically regarding this, members of the SLICC group initiated the International Registry for Biologics in SLE (IRBIS). The objective of this study was to analyse the use of biologics in SLE, and assess results achieved with the most commonly used off-label biologic, rituximab (RTX). Materials and methods IRBIS investigators were asked to provide retrospective data on all patients treated with a biologic for SLE at their center. Standardised case report forms were used to collect demographic, disease-specifi c and treatment data at the time of biologic initiation and at yearly follow-up. Data from the fi rst 23 reporting centers are presented. Results Three hundred and fi fty-nine patients were treated off-label with RTX, and additional groups of patients were exposed to belimumab (n=44), epratuzumab (n=21), abatacept (n=4), etanercept (n=3) and adalimumab (n=1). For the RTX treated group, age (mean±SD) was 41.3±13.3 and 91% were female. The majority (76%) were Caucasian, and smaller proportions were Southeast Asian, Asian/Indian, AfricanAmerican, Latino, Afro-Caribbean or other (each <10%). Disease duration when RTX was initiated was 9.2±7.8 years. SLEDAI at start was 11.3±7.6, SLICC-damage index 1.4±1.5 and glucocorticoid dosage 17.0±15.2 mg. Most patients (78%) had been treated with one or two different immunosuppressives (ISs) prior to RTX, and the remaining with three to fi ve ISs. Two dosing regimens were used for RTX: 375 mg/m2x4 (52%) and 1000 mgx2 (48%). The major organ manifestations leading to RTX treatment were lupus nephritis (LN, 48%), haematological (21%), musculoskeletal, skin disease, CNS and other (each <10%). At 1-year follow-up both SLEDAI and GC dose had decreased (4.2±3.5 (n=106) and 7.9±7.0mg (n=89), respectively, paired samples, p<0.0001 for both comparisons). Exclusion of patients started on additional ISs (n=24) did not change SLEDAI or GC dose signifi cantly. SLEDAI at baseline was higher in LN than in non-LN patients but similar at follow-up. Overall, the 1000 mgx2 was more often used but both dosing regimens appeared equally effective in LN. Conclusions RTX was the off-label biologic most commonly used in this multi-center international lupus cohort and was used for LN as well as for other SLE manifestations. At oneyear-follow-up both lupus activity and concomitant glucocorticoid dosage had decreased even when no other IS treatments had been introduced. The two RTX dosing regimes appeared equally effective for LN treatment, but fi rm conclusions cannot be made from these observational data.on 29 August 2018 by guest. Protected by copyright.
Celiac disease (CD) is an autoimmune systemic condition -the only one with a well-established origin-resulting from permanent gluten intolerance, which primarily involves the gut. It is characterized by the presence of chronic mucosal inflammation in the small bowel, which may be associated with highly variable clinical manifestations. It may develop at any age, both during childhood and adolescence, and is relatively common in th adult; it is increasingly diagnosed even in elderly patients (up to 20% of patients are older than 60 years at the time of diagnosis).The causal agent is gluten, a protein preset in cereal -mainly wheat, barley, rye and oats, but not corn-flour. It affects predisposed individuals whose most susceptible genetic features are identified in the HLA-II histocompatibility system of human leukocytes, and whose most common markers include HLA-DQ2 (90%) and HLA-DQ8 (5-10%). However, such genetic markers are a necessary but insufficient condition, since with a non-negligible frequency (5-10%) celiac patients are encountered who are DQ2-and DQ8-negative, and thus other still not well-established genotypes may exist that probably correspond to the class-I HLA system, including MICA and MICB.Most affected individuals show sustained clinical remission when strictly on a gluten-free diet (GFD), which must be kept indefinitely for life as a result of this illness having genetic grounds.Until recently, CD was considered a rare disease, but is known nowadays to be universally distributed, to involve all races, and to be one of the most common genetic diseases with a mean prevalence of 1-2% in the general population, being clearly subestimated and subdiagnosed worldwide. This would represent an estimate of 3 million people affected by CD in Europe, and around 450,000 in the whole of Spain (only around 45,000 are currently diagnosed).Selected ethnic groups may have a prevalence lower than that suggested for the Caucasian race but not far from them, as the worldwide distribution of CD is pretty homogeneous, the only exception extant being the Saharan population with a mean estimate of 10%, the highest heard of thus far (1-6).Most common gastrointestinal manifestations include frequent abdominal pain and distension episodes, prolonged digestion, and altered bowel habit (diarrhea and/or constipation) in association with trace element, vitamin and mineral deficiencies, this being the reason that it is often accompanied by anemia, osteoporosis, and other extra-intestinal manifestations.While diarrhea was almost considered a necessary symptom, this is not the case in the adult, and up to 50% of patients have constipation predominantly, which on many an occasion becomes refractory to all sorts of therapy used. It is also fit to remember that up to 30% of celiac patients have obvious overweight at diagnosis. Celiac disease in the adult1130-0108/2006/98/6/397-407 REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS Copyright © 2006 ARÁN EDICIONES, S. L. REV ESP ENFERM DIG (Madrid) Vol. 98, N.°6, pp. 397-407, 2006 E d i t o...
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