Severe Disease Activity Research Articles

Ml28133 -A Multicenter, Open-Label, Long-Term Extension Study of WA 19926 to Describe Safety During Treatment with Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Abstract Introduction. Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study wasto assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods. ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11(84.61%) female. The average age of patients was 53.27+/−10.68. Patients received 8mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results. Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion. The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease.

Active inflammatory bowel disease (IBD) during conception and pregnancy may increase the risk of adverse birth outcomes. Former studies have examined heterogeneous groups of women with varying degrees of IBD severity. We aimed to examine the effect of active IBD on birth outcomes in a more homogeneous group of women with a moderate to severe disease course. Since in Denmark, moderate to severe IBD is an indication for use of anti-tumor necrosis factor-α therapy, we examined all women who used anti-tumor necrosis factor therapy during pregnancy. We identified a nationwide cohort of 219 singleton pregnancies in women treated with anti-tumor necrosis factor-α therapy during pregnancy (2005-2014). Pregnancies with clinical disease activity (65.8%) constituted the exposed cohort and pregnancies without disease activity constituted the unexposed (34.2%). Disease activity scores were supported by levels of fecal calprotectin. Outcomes included low birth weight, preterm birth, and congenital anomalies. In women with IBD, disease activity was associated with adjusted odds ratio of low birth weight and preterm birth; 2.05 (95% confidence interval, 0.37-11.35) and 2.64 (95% confidence interval, 0.85-8.17), respectively. In those with clinical moderate to severe disease activity, the odds ratio for preterm birth was 3.60 (95% confidence interval, 1.14-11.36). In women with ulcerative colitis and disease activity, 19.5% had a child with low birth weight and 29.3% gave birth preterm. In women with moderate to severe IBD, 66% experienced disease activity during pregnancy. In those with the highest degree of disease activity, the risk of preterm birth was increased 3 to 4 folds. The proportion of adverse birth outcomes was high, particularly among women with ulcerative colitis and disease activity.

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn\u2019s disease, and clinical prognosis in inflammatory bowel disease

BackgroundCathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients.MethodsSerum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development.ResultsSerum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6–18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients.ConclusionCo-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

The effect of TNF-a antagonists on aortic stiffness and wave reflections: a meta-analysis.

Patients with rheumatoid arthritis (RA) have higher aortic stiffness and cardiovascular risk. Tumor necrosis factor alpha (TNF-a) antagonists reduce inflammation in RA and are indicated for the treatment of patients with severe active rheumatoid disease. However, it is debatable if they have favorable effects on cardiovascular health. The present meta-analysis evaluates the effect of TNF-a antagonists on aortic stiffness and wave reflections, predictors of cardiovascular events and mortality, in RA patients. A search of PubMed, Cohrane, and Embase databases was conducted to identify studies into the effect of TNF-a antagonists on aortic stiffness in RA patients. Aortic stiffness and wave reflections were assessed by aortic (carotid-femoral [cf]) pulse wave velocity (PWV) and augmentation index (AIx), respectively. cfPWV significantly improved following TNF-a antagonist treatment (mean change: -0.53m/s, 95% CI: -0.833 to -0.218, p=0.001), independently of age and clinical response to treatment. A more prominent reduction in cfPWV was associated with etanercept/adalimumab (mean difference: -0.62m/s, 95% CI: -0.968 to -0.272m/s, p<0.001) versus infliximab (mean difference: -0.193m/s, 95% CI: -0.847 to 0.462m/s, p=0.564). TNF-a antagonist treatment induced a significant improvement in AIx (mean change: -1.48%, 95% CI: -2.89 to -0.078%, p=0.039), but this reduction was influenced by age and clinical response to treatment. The balance of evidence suggests that TNF-a antagonists may have a beneficial effect on aortic stiffness and, therefore, on cardiovascular risk. However, larger, longitudinal studies are warranted to confirm such findings.

A rising incidence and poorer male outcomes characterise early onset paediatric inflammatory bowel disease.

The incidence of paediatric inflammatory bowel disease diagnosed before age 10years is reportedly increasing, but national data are limited. To characterise the epidemiology, phenotype and clinical outcomes of children diagnosed with inflammatory bowel disease before age 10years, and compare with data from children diagnosed aged 10-16years. A review of all Irish cases of early onset inflammatory bowel disease (diagnosis <10years, EO-IBD) presenting between January 2000 and December 2014 was undertaken and compared to a cohort of later onset paediatric inflammatory bowel disease patients (diagnosis between 10 and 16years, LO-IBD). Diagnostic investigations, phenotype, treatments, and long-term clinical and surgical outcomes were analysed. One hundred and ninety children (99 male) with EO-IBD were identified; 92 (48%) CD, 77 (41%) UC and 21 (11%) IBDU. The incidence of EO-IBD increased by 0.6 per 100000 per year (0.8-3.2 per 100000 per year), with a significant increase in UC by 0.06 per 100000 per year (P=.02). Males with CD had more upper GI disease (L4a; 48% vs 21%; P=.007), more extensive disease distribution (L3±L4; 31% vs 11%; P=.05) and more severe disease activity at presentation (52% vs 31%; P=.05) than females. Fewer patients with early onset than later onset Crohn's disease had ileocolonic disease (L3; 10% vs 20%; P<.001). More relapses were observed in the first year post-diagnosis in early onset than later onset IBD (1.02 vs 0.5 mean relapses; P<.001). EO-IBD is increasing in incidence. Males have more extensive and severe disease phenotypes, and younger patients have higher relapse rates than older children. Further research to explain these findings is warranted.

Clinical and demographic factors associated with change and maintenance of disease severity in a large registry of patients with rheumatoid arthritis

BackgroundWe examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA).MethodsData from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low (≤10), moderate (>10 and ≤22), and severe (>22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were used to examine impacts of covariates (time between visits, chronological year, disease duration, age) on disease states.ResultsData from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients (46,534 visits) with regular visits (every 3–9 months) were analyzed. The probability of moving from moderate to low or severe disease by next visit was 47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25 months (95% confidence interval: 4.18–4.32). Transition probabilities showed 20% of patients with low disease activity moved to moderate or severe disease within 6 months; >35% of patients with moderate disease remained in moderate disease after 6 months. Results were similar for the regular-visit sub-cohort. Significant interactions with prior disease state were seen with chronological year and disease duration.ConclusionA substantial proportion of patients remain in moderate disease, emphasizing the need for treat-to-target strategies for RA patients.

Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis.

Patients with ulcerative colitis often report fatigue. To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n = 133) or being in deep remission (n = 155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. The prevalence of high fatigue (general fatigue ≥ 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1-12.2)), iron deficiency (OR 2.5 (1.2-5.1)), active disease (OR 2.2 (1.2-3.9)) and female gender (OR 2.1 (1.1-3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission.

FLT-1 gene polymorphisms and protein expression profile in rheumatoid arthritis.

ObjectivesInflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different “angiogenic diseases” suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.MethodsThe FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated.ResultsThe FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D’ = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.ConclusionFLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.

Thyroid-associated Ophthalmopathy.

Thyroid-associated ophthalmopathy is the most frequent extrathyroidal involvement of Graves’ disease but it sometimes occurs in euthyroid or hypothyroid patients. Thyroid-associated ophthalmopathy is an autoimmune disorder, but its pathogenesis is not completely understood. Autoimmunity against putative antigens shared by the thyroid and the orbit plays a role in the pathogenesis of disease. There is an increased volume of extraocular muscles, orbital connective and adipose tissues. Clinical findings of thyroid-associated ophthalmopathy are soft tissue involvement, eyelid retraction, proptosis, compressive optic neuropathy, and restrictive myopathy. To assess the activity of the ophthalmopathy and response to treatment, clinical activity score, which includes manifestations reflecting inflammatory changes, can be used. Supportive approaches can control symptoms and signs in mild cases. In severe active disease, systemic steroid and/or orbital radiotherapy are the main treatments. In inactive disease with proptosis, orbital decompression can be preferred. Miscellaneous treatments such as immunosuppressive drugs, somatostatin analogs, plasmapheresis, intravenous immunoglobulins and anticytokine therapies have been used in patients who are resistant to conventional treatments. Rehabilitative surgeries are often needed after treatment.

Sonographic Characteristics of Extensor Tendon Abnormalities and Relationship With Joint Disease Activity in Rheumatoid Arthritis: A Pilot Study.

To characterize abnormalities in the dorsal extensor tendons of the hand and determine the importance of these findings in rheumatoid arthritis. A retrospective cross-sectional study was done on 26 patients with rheumatoid arthritis who had sonography of their hands. B-mode and power Doppler joint activity were scored, and the extensor tendons were examined for B-mode changes and power Doppler signals. B-mode changes included anechoic fluid around tendons, hypoechoic tissue around tendons, paratendon tissue and tendon thickening, as well as vascularity around the tendon, for which peritendon power Doppler signals were recorded. Forty-one hands and 205 joints were reviewed. Anechoic fluid around the tendons and peritendon power Doppler signals were observed in 41% and 39%, respectively; 44% and 28% of patients had B-mode and power Doppler scores in the upper tertile, respectively. For both B-mode and power Doppler scores, 3 categories or tertiles were created, 0 to 0.9, 1 to 1.9, and 2 to 3. We reported the percentage of patients with power Doppler and B-mode scores in this category. The severity of synovitis was associated with anechoic fluid around the tendons and peritendon power Doppler signals according to the Cochran-Mantel-Haenszel test. The common odds ratio was 3.52 (95% confidence interval, 1.45- 8.53) for anechoic fluid around the tendons and severe synovitis. The common odds ratio was 2.52 (95% confidence interval, 1.13-5.63) for peritendon power Doppler signals and severe synovitis. Findings at the dorsal extensor tendons were anechoic fluid around tendons, hypoechoic tissue around tendons, peritendon power Doppler signals, and tendon thickening. Patients with anechoic fluid and power Doppler signals were found to have more severe disease activity at the joints based on B-mode and power Doppler scores.

Belimumab in systemic lupus erythematosus (SLE): evidence-to-date and clinical usefulness.

Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease with multiple presentations, whose management presents many challenges. Many disease modifying or immunosuppressive drugs have been used with limited success, especially in patients with more severe disease activity. Belimumab is the first drug to be approved specifically for the treatment of SLE in more than 50 years. By blocking the B-cell activating factor, it interferes in B-cell differentiation and survival. Here we consider the results of the clinical trials that led to its approval, as well as the post-hoc analyses, follow-up studies and the current trials.

Changes in health-related quality of life over a 1-year follow-up period in children with inflammatory bowel disease.

Little is known about disease-specific health-related quality-of-life (HRQoL) changes over time in paediatric patients with inflammatory bowel disease (IBD), and about their associations with baseline medical characteristics. In this study, 153 paediatric patients with IBD from the multicentre prospective Swiss IBD cohort study were included at baseline. Of these, 90 patients were analysed at a 1-year follow-up. Medical data were extracted from hospital records, while HRQoL data were measured using the standardized, self-report disease-specific IMPACT-III questionnaire. The IBD diagnosis of the included children was made an average of 2.0 years before their baseline assessment. Over the 1-year follow-up period, a significant increase in overall HRQoL and in the HRQoL domain 'physical functioning' was evident. On multivariate analysis, overall HRQoL changes over time were predicted by baseline HRQoL, baseline disease activity, and disease activity changes over time. HRQoL improvements were significantly associated with decreases in physician-assessed disease activity. Children reporting a low baseline HRQoL and children with inactive or mildly-active disease experienced greater improvements. Children with more severe baseline disease activity had the greatest risk for HRQoL deterioration over the 1-year follow-up period. However, among possible factors that might influence HRQoL changes over time, the child's medical characteristics explained only a small proportion of their variability in our sample. We, therefore, recommend that researchers and clinicians focus on factors that are not incorporated within the multidimensional HRQoL concept if they seek to gain better insights into factors that influence HRQoL changes over time in children with IBD.

Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease.

Minimising placebo response is essential for drug development. To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

55: EVALUATING THE PREVALENCE OF ANEMIA AND ASSOCIATED FACTORS IN PATIENTS WITH ULCERATIVE COLITIS

Background and aims:IBD includes Crohn's disease and ulcerative colitis is 2 inflammations. Symptoms of IBD include abdominal pain, diarrhea and fever, but symptoms of the intestinal tract or other organ...

Experience with Biosimilar Infliximab (Remsima®) in Norway

Background: The first monoclonal antibody biosimilar to be used in clinical practice is the tumour necrosis factor-alpha inhibitor Remsima® (CT-P13). The drug is approved for all indications as the originator infliximab (Remicade®) although clinical efficacy has been demonstrated only in rheumatic diseases. Since the fall of 2013, Remsima® has been available in Norway and from January 2014, it has been the drug of choice when initiating biological treatment in biologics naïve patients with inflammatory bowel disease (IBD). However, many gastroenterologists have been greatly concerned about the extrapolation of indication. Switching between Remsima® and the innovator product is another issue that has been discussed. Key Messages: Good efficacy, tolerability and safety were demonstrated in a prospective observational study of IBD patients with moderate to severe disease activity. After 14 weeks of treatment there was a significant reduction in the Harvey Bradshaw index in patients with Crohns disease (CD) and reduction in the partial Mayo score and simple clinical colitis activity index in patients with ulcerative colitis. In both patient groups, there was also a significant reduction in fecal calprotectin and C-reactive protein (CRP). In another observational study, IBD patients on maintenance treatment with Remicade® were switched to Remsima®. By comparing values before and after switch, no changes in activity indices, CRP or calprotectin were observed. However, a significant increase in infliximab trough levels was shown in the CD group. No unexpected adverse events occurred after switching. Conclusions: Based on our experience in Norway, Remsima® seems to be efficacious and well tolerated in IBD. The increasing use of Remsima® in clinical practice has also contributed to significant cost savings on the health budget. Results from the NOR-SWITCH study will be available during 2016 and will hopefully contribute to answer some of the important questions that have been raised following the introduction of biosimilars as a treatment option for IBD and other immune-mediated inflammatory diseases.

Risk factors for sexual dysfunction in Egyptian patients with rheumatoid arthritis and its relation to disease activity

Aim of the workTo assess risk factors for sexual dysfunction in married rheumatoid arthritis (RA) patients. Patients and methods216 RA (187 females and 29 males) and 187 matched healthy controls were included. Sexual function in male was assessed by modified International Index of Erectile Function Questionnaire (IIEF questionnaire) including: erectile function, sexual desire (libido), orgasmic and ejaculatory problems. For females, in addition to questions about libido, orgasmic problems, frequency of sexual intercourse and dyspareunia were considered. Disease activity scores (DAS-28) and modified health assessment questionnaire (mHAQ) were calculated. ResultsThe mean age of the patients was 45.2±12.1years and disease duration was 8.2±7.6years. All sexual dysfunction parameters were significantly higher in RA than in the controls. Patients with sexual dysfunction were older (p=0.008), illiterate (p=0.04), diabetics (p=0.004), hypercholesterolemics (p=0.002), had high ESR (45.1±21.6mm/1sth) (p<0.001), longer MS duration (39.3±40.9minutes) (p=0.01), had high DAS28 (p<0.001) and mHAQ (p=0.004) and used higher doses of leflunomide (p=0.01). Multivariate regression analysis revealed that the presence of DM (OR 5.1; 95%CI 1.3–19.4), hypertension (OR 3.5; 95%CI 1.9–6.1), hypercholesterolemia (OR 3.6; 95%CI 1.5–8.2), older age (⩾45years) (OR 2.4; 95%CI 1.3–4.5) (p=0.003), active RA patients were associated with a higher risk of sexual dysfunction (OR 2.7; 95%CI 1.09–6.5) (p=0.03); OR increased to 5.6 (95%CI 2.7–11.8) in patients with severe disease activity. ConclusionDM, hypertension, hypercholesterolemia, older age and high disease activity in RA increase the risk of sexual dysfunction.

Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry

According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician’s preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into “first-” and “second-line” bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p < 0.0001). Positive latent tuberculosis screening was associated with first-line ABA (p = 0.002). Methotrexate (MTX) combination therapy was lower in the TCZ group (p = 0.02). The type (dyslipidemia, hypertension, pulmonary disease) and the number of comorbidities influenced the choice towards ABA (p = 0.01). Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.

A Potential of sFasL in Preventing Gland Injury in Sjogren's Syndrome.

Fas and its ligand FasL, members of tumor necrosis factor receptor superfamily, have been implicated in the process of cell apoptosis. FasL consists of two forms, membrane FasL (mFasL) and soluble FasL (sFasL). sFasL can be produced by mFasL cleaved by matrix metalloproteinases (MMP) and also reveals a role for binding to Fas which is expressed on cell surface. Although Fas/FasL axis has been implicated in a variety of diseases, its role in Sjogren's syndrome still remains ill defined. In this study, we investigated the potential of sFasL in the pathogenesis of Sjogren's syndrome (SS). We found that the serum levels of sFasL in SS patients were significantly lower than healthy subjects. Moreover, serum levels of sFasL in patients with mild disease activity were higher than patients with severe disease activity. There is a positive correlation of the serum level of sFasL with uptake index of parotid gland in our expectation. In addition, liver injury involvement in SS patients showed decreased level of sFasL. Furthermore, we here also observed that the protective cytokine IL-10 expression was positively correlated with sFasL expression. Thus, our results here suggest a potential of sFasL in maintaining gland organ homeostasis.

Discordant inflammation and pain in early and established rheumatoid arthritis: Latent Class Analysis of Early Rheumatoid Arthritis Network and British Society for Rheumatology Biologics Register data.

BackgroundRheumatoid arthritis (RA) disease activity is often measured using the 28-joint Disease Activity Score (DAS28). We aimed to identify and independently verify subgroups of people with RA that may be discordant with respect to self-reported and objective disease state, with potentially different clinical needs.MethodsData were derived from three cohorts: (1) the Early Rheumatoid Arthritis Network (ERAN) and the British Society for Rheumatology Biologics Register (BSRBR), (2) those commencing tumour necrosis factor (TNF)-α inhibitors and (3) those using non-biologic drugs. In latent class analysis, we used variables related to pain, central pain mechanisms or inflammation (pain, vitality, mental health, erythrocyte sedimentation rate, swollen joint count, tender joint count, visual analogue scale of general health). Clinically relevant outcomes were examined.ResultsFive, four and four latent classes were found in the ERAN, BSRBR TNF inhibitor and non-biologic cohorts, respectively. The proportions of people assigned with >80% probability into latent classes were 76%, 58% and 72% in the ERAN, TNF inhibitor and non-biologic cohorts, respectively. The latent classes displayed either concordance between measures indicative of mild, moderate or severe disease activity; discordantly worse patient-reported measures despite less markedly elevated inflammation; or discordantly less severe patient-reported measures despite elevated inflammation. Latent classes with discordantly worse patient-reported measures represented 12%, 40% and 21% of the ERAN, TNF inhibitor and non-biologic cohorts, respectively; contained more females; and showed worse function. In those latent classes with worse scores at baseline, DAS28 and function improved over 1 year (p < 0.001 for all comparisons), and scores differed less at follow-up than at baseline.ConclusionsDiscordant latent classes can be identified in people with RA, and these findings are robust across three cohorts with varying disease duration and activity. These findings could be used to identify a sizeable subgroup of people with RA who might gain added benefit from pain management strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1186-8) contains supplementary material, which is available to authorized users.

Clinical Efficacy of Beclomethasone Dipropionate in Korean Patients with Ulcerative Colitis.

PurposeOur aim was to evaluate the efficacy and safety of oral beclomethasone dipropionate (BDP) in Korean patients with ulcerative colitis (UC).Materials and MethodsThe medical records of patients with active UC who were treated with BDP were retrospectively reviewed. Partial Mayo Clinic score (pMS) was calculated to determine disease activity. After 4 weeks of therapy, clinical remission, clinical response, and response failure rates were evaluated. Clinical remission was defined as a post-treatment pMS of 0 or 1, clinical response as a decrease of two of three points in pMS and >30% from baseline, and response failure as a lack of clinical response. Also, we considered that clinical remission was included in clinical response.ResultsBetween July 2013 and April 2015, 95 patients with UC received BDP therapy at our institution (median age, 44 years; range, 12–81 years). After 4 weeks of therapy, clinical remission and clinical response rates were 50.5% and 73.7%, respectively. Mean change of pMS before and after BDP therapy was 2.4. There was no significant side effect reported. In multivariate analysis, disease activity was the only factor associated with a favorable response. Clinical remission rate was significantly higher in the mild disease activity group (66.7%) than that in the moderate or severe disease activity group (41.9%) (p=0.024).ConclusionBDP is efficacious in inducing a clinical response or remission in Korean patients with UC. Patients with mild UC were more likely to be in remission than those with moderate or severe UC after receiving BDP for 4 weeks. BDP exhibited a good safety profile.