Long-term anti-TNFα therapy for ankylosing spondylitis in two patients with chronic HBV infection

Anti-TNFα therapy for rheumatic diseases appears to be safe in patients with chronic hepatitis C. However, the administration of anti-TNFα agents without initiation of prophylactic antiviral therapy (lamivudine 100 mg/day) in patients with chronic HBV infection results in exacerbation of liver disease. In this report, we describe our experience of long-term anti-TNFα therapy for ankylosing spondylitis in two inactive HBsAg carriers without preemptive antiviral treatment.     

Dendritic cells: a new horizon in cell therapy for inflammatory bowel disease?

Autoimmune diseases, or immune-mediated diseases, are characterized by loss of tolerance to autoantigens and immune system activation causing damage to one or multiple organs. The mechanisms through which this abnormal immune response is started and maintained are not fully established. The therapeutic approach to these diseases is generally based on corticosteroids, immunomodulators, and monoclonal antibodies. Given the exceptional capacity of dendritic cells to induce immunogenicity, early results in humans for the treatment of tumors (melanoma) or infections (HIV) with immunogenic dendritic cells have recently been obtained. Identification of dendritic cells with tolerogenic capacity and the results in experimental models of autoimmune diseases (autoimmune encephalomyelitis, diabetes mellitus, colitis) suggests that treatment with tolerogenic dendritic cells could be a beneficial therapeutic alternative in the treatment of autoimmune diseases or immune-mediated diseases such as Crohn's disease.     

Regional differences in anti-TNF-α therapy and surgery in the treatment of inflammatory bowel disease patients: a Norwegian nationwide cohort study

Background and aims: During the last decades, substantial progress has been made in both medical and surgical treatment of inflammatory bowel disease (IBD). The aim of this study was to determine the use of anti-TNFs and surgery during the first 3 years after diagnosis in IBD patients across the four health regions in Norway using nationwide patient registry data.

Methods: This study used nationwide data from the Norwegian Patient Registry. Cumulative incidence of anti-TNF exposure and major surgery was calculated for patients diagnosed in 2010–2012. The analyses were stratified by diagnosis and health region. All patients were followed for an equal period of 3 years from diagnosis.

Results: The study population included 8,257 IBD patients first registered between 2010 and 2012, of whom 2,829 were diagnosed with Crohn’s disease (CD) and 5,428 with ulcerative colitis (UC). Across Norway’s health regions, the cumulative incidence of major surgery after 3 years varied from 11.4% to 17.1% for CD and from 4.6% to 6.9% for UC. The cumulative incidence of anti-TNF exposure varied from 20.9% to 31.4% for CD and from 8.0% to 13.5% for UC. The region with the lowest anti-TNF use had the highest surgery rates for both UC and CD.

Conclusions: Cumulative incidence of anti-TNF exposure and surgery varied significantly across Norway’s health regions during the three first years after IBD diagnosis.     

Effects of anti–TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease

BackgroundTumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti–TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown.MethodsAnalytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy.Results29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ± SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98–8.45) and elevated CRP (OR 3.45; 95CI 1.29–9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07–9.16).ConclusionsControlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.     

Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor?

BACKGROUND: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. METHODS: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC). 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. RESULTS: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years: P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. CONCLUSIONS: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect.     

High and increasing prevalence of inflammatory bowel disease in Finland with a clear North–South difference

Background and aimInflammatory bowel disease (IBD) prevalence has increased and a North–South gradient has been reported. We estimated the nationwide prevalence of IBD, ulcerative colitis (UC) and Crohn's disease (CD) in 1993, and prevalence of IBD in 2008, and assessed the geographical distribution of IBD in Finland. In addition, we investigated the vitamin D levels in a study population from a large, nationally representative health examination survey, the Health 2000 Survey.MethodsThe register study for prevalences included all patients who had special reimbursement of medications for IBD in the years 1993 (n = 10,958) and 2008 (31,703). The study for D-vitamin measurement consisted of 6134 persons who had participated in the Health 2000 Survey.ResultsThe nationwide point prevalence of IBD in 1993 was 216 per 100,000 inhabitants, and 595 in 2008. In 1993, the prevalence of UC (177) was fourfold higher than the prevalence of CD (38). The prevalence of IBD and UC in Finland increased from South to North. For CD, no geographical variation could be demonstrated. In the Health 2000 survey, vitamin D levels were lower in Northern than in Southern Finland.ConclusionsFinland belongs to high prevalence area of IBD and this prevalence has increased nearly threefold during the past 15 years. A clear North–South gradient has been shown for IBD and UC, but not for CD. Slightly lower vitamin D levels in Northern Finland may be associated with the observed higher prevalence of IBD there.     

Is neutropenia required for effective maintenance of remission during azathioprine therapy in inflammatory bowel disease?

BACKGROUND: Azathioprine is an effective treatment for maintaining remission in inflammatory bowel disease (IBD). It is a matter of debate as to whether neutropenia is required during azathioprine therapy to achieve more effective disease remission. We evaluated whether neutropenia during azathioprine therapy reduced relapse rates in IBD patients. PATIENTS AND METHODS: This retrospective study was based on a total of 173 IBD (96 Crohn's disease (CD), 77 ulcerative colitis (UC)) patients who were stable on azathioprine for a minimum of 6 months. Median duration of follow-up was 4.0 years (range 0.6-21 years). The lowest neutrophil counts during treatment for these patients were recorded. Relapse rates per year of follow-up were compared in non-neutropenic patients (neutrophil count > 2.5 x 10(9), n = 129) and neutropenic patients (neutrophil count < or = 2.5 x 10(9), n = 44) groups, and survival curves for cumulative remission rates compared by log-rank test. RESULTS: Mean relapse rate per year of follow-up for the non-neutropenic group was 0.19/year (SD = 0.37/year) compared with the neutropenic group 0.28/year (SD = 0.43/year) (P = NS). Analysis was performed on UC and CD subgroups, and relapse rates were not significantly different. The cumulative remission per cent determined by Kaplan-Meier survival analysis showed no difference between non-neutropenic and neutropenic groups by log-rank analysis, for UC and CD as well as for all IBD patients. CONCLUSION: Neutropenia < or = 2.5 x 10(9) while on azathioprine does not reduce the relapse rates of IBD patients who were established on azathioprine therapy compared with neutrophil counts > 2.5 x 10(9).     

Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants

BackgroundFew studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics.AimsTo evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options.MethodsAll consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained database.ResultsTwenty-four patients were included. Four weeks after initiation of mycophenolate mofetil therapy, a steroid-free remission was achieved in 4 patients (16.7%), while a clinical response in 13 (54.1%). At the end of follow-up, 12 patients (50.0%) remained on mycophenolate mofetil. Six achieved and maintained steroid-free remission throughout the study period (25.0%), and a further 6 patients (25.0%) achieved a clinical response with complete discontinuation of steroids. Twelve patients (50.0%) were considered as treatment failure, and five of them underwent surgery.ConclusionsThis is the first experience reporting a clinical benefit and tolerability of mycophenolate mofetil in patients with inflammatory bowel disease and multiple previous failures to other immunosuppressants and/or biologics.