Anti-tumor Necrosis Factor Alpha Therapy Research Articles

Assessment of subclinical atherosclerosis in psoriatic arthritis patients without clinically overt cardiovascular disease or traditional atherosclerosis risk factors.

Cardiovascular disease (CVD) is more prevalent in almost all patients with chronic inflammatory musculoskeletal diseases than in their healthy counterparts. The aim of this study was to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. A total of 30 patients with PsA, 30 patients with RA, and 30 healthy controls were enrolled in this parallel group study. Demographic, clinical, and laboratory data of the groups were recorded. The Disease Activity Score-28 tool was used for joint assessment. The erythrocyte sedimentation rate and C-reactive protein level were measured as acute phase reactants. Flow-mediated dilatation (FMD) and carotid intima media thickness (CIMT) were also measured in all participants. The median duration of disease in patients with PsA was 60 months (range: 8-216 months). A total of 22 of 30 (73.3%) PsA patients had a diagnosis of psoriasis and 13 (48.1%) had active disease. The study groups were similar with regard to age, gender, and body mass index data. In all, 23 (76.7%) of the PsA patients and 5 (16.7%) of the RA patients were using an anti-tumor necrosis factor alpha therapy (p<0.001). The FMD percentage was significantly smaller in both the PsA and the RA patients than in the healthy controls (p<0.001). The median CIMT was greater in the RA patients compared with the PsA patients and the healthy controls (p=0.008). There was no significant difference in FMD or CIMT between patients with and without an active joint lesion. Endothelial functions were impaired in PsA, as in RA, in the absence of conventional risk factors or overt CVD. This finding may show a potential association between PsA, atherosclerosis, and CVD.

Vaccinations in immunosuppressive-dependent pediatric inflammatory bowel disease.

AIMTo determine the vaccination rates in pediatric immunosuppression-dependent inflammatory bowel disease (IBD) and review the safety and efficacy of vaccinations in this population.METHODSThe electronic medical records from October 2009 to December 2015 of patients diagnosed with IBD at 10 years of age or younger and prescribed anti-tumor necrosis factor alpha (anti-TNF-α) therapy were reviewed for clinical history, medication history, vaccination history, and hepatitis B and varicella titers. Literature discussing vaccination response in IBD patients were identified through search of the MEDLINE database and reviewed using the key words “inflammatory bowel disease”, “immunization”, “vaccination”, “pneumococcal”, “varicella”, and “hepatitis B”. Non-human and non-English language studies were excluded. Search results were reviewed by authors to select articles that addressed safety and efficacy of immunizations in inflammatory bowel disease.RESULTSA total of 51 patients diagnosed with IBD prior to the age of 10 and receiving anti-TNF-α therapy were identified. Thirty-three percent of patients (17/51) had incomplete or no documentation of vaccinations. Sixteen case reports, cohort studies, cross-sectional studies, and randomized trials were determined through review of the literature to describe the safety and efficacy of hepatitis B, pneumococcal, and varicella immunizations in adult and pediatric patients with IBD. These studies showed that patients safely tolerated the vaccines without significant adverse effects. Importantly, IBD patients receiving immunosuppressive medications, particularly anti-TNF-α treatment, have decreased vaccine response compared to controls. However, the majority of patients are still able to achieve protective levels of specific antibodies.CONCLUSIONImmunizations have been shown to be well-tolerated and protective immunity can be achieved in patients with IBD requiring immunosuppressive therapy.

Anti-TNF-α Use During the Third Trimester of Pregnancy in Women with Moderate-severe Inflammatory Bowel Disease and the Risk of Preterm Birth and Low Birth Weight.

Little knowledge exists about the association between anti-tumor necrosis factor-alpha (anti-TNF-α) therapy for inflammatory bowel disease during late pregnancy and adverse birth outcomes. We aimed to examine whether treatment with anti-TNF-α during the third trimester affected preterm birth and low birth weight (LBW), compared with women who discontinued anti-TNF-α therapy before the third trimester. We identified a nationwide cohort of 219 women treated with anti-TNF-α during the pregnancy period and reviewed the medical records to extract clinical details. The exposed cohort (n = 113, 51.6%) constituted pregnancies exposed to anti-TNF-α during the third trimester, and the unexposed cohort (n = 106, 48.4%) constituted pregnancies with no anti-TNF-α during the third trimester. The association between anti-TNF-α therapy in the third trimester and adverse birth outcomes was studied (1) in those women who had clinical disease activity during pregnancy and (2) in women who had no clinical disease activity during pregnancy. In women with disease activity, treated with anti-TNF-α during the third trimester, we found an adjusted odds ratio of 2.23 (95% confidence interval [CI], 0.80-6.20) for preterm birth and 1.16 (95% CI, 0.26-5.23) for LBW. Among women without disease activity, treated with anti-TNF-α therapy during the third trimester, we found an adjusted odds ratio of 3.36 (95% CI, 0.31-36.46) for preterm birth and 0.86 (95% CI, 0.05-14.95) for LBW. For anti-TNF-α therapy in the third trimester, we found no statistically significant increased risk of either LBW or preterm birth.

Tocilizumab for the Treatment of Behçet Uveitis that Failed Interferon Alpha and Anti-Tumor Necrosis Factor-Alpha Therapy

ABSTRACTPurpose: To report the results of tocilizumab (TCZ) treatment in patients with Behçet uveitis (BU) who had failed conventional, interferon alpha, and anti-Tumor necrosis factor-alpha therapy.Methods: We reviewed the records of five patients with BU treated with monthly infusions of TCZ 8 mg/kg. Outcome measures were visual acuity, anterior chamber cells, laser flare meter (LFM) readings, vitreous haze, central macular thickness (CMT), and fluorescein angiography (FA) score.Results: The clinical inactivity of BU and 20/50 or better vision were achieved in three female and two male patients treated with TCZ for 5–19 months. The mean LFM reading was reduced from 15.4 ± 2.7 to 5.0 ± 0.9 ph/ms; the mean CMT from 324.7 ± 36.6 µm to 280.2 ± 34.1 µm; and the mean FA score from 20.6 ± 5.4 to 9.3 ± 4.5 µm at the last visit. The only side effect was a slight elevation of the total cholesterol level in one patient.Conclusions: Tocilizumab may be a safe and effective therapeutic option for refractory BU.

Post-Marketing Safety Experience of Vedolizumab in Patients With Pre-existing Viral Hepatitis

Introduction: Systemic immunosuppressive treatment can reactivate the latent hepatitis virus.1 The gut selectivity of vedolizumab (VDZ) may be associated with a lower risk of hepatitis virus reactivation than anti-tumor necrosis factor-alpha agents. The VDZ US Product Label advises caution in patients with a history of recurring severe infections.2 As VDZ clinical trials excluded patients with chronic viral hepatitis B or C, there are no clinical trial data available in this population. Here, we describe the VDZ safety experience in patients with pre-existing hepatitis B or C in the post-marketing setting. Methods: Adverse events (AEs) were identified from the VDZ Global Safety Database (data cut May 20, 2014 to Nov 19, 2016) and included if patients' medical history or concurrent conditions included a Medical Dictionary for Regulatory Activities (MedDRA) preferred term of hepatitis B or C infection. Results: In the context of ˜77,382 patient-years of VDZ post-marketing exposure (30,470 AEs), 15 patients (n=7 Crohn's disease; n=6 ulcerative colitis; n=2 indication not reported [NR]) with hepatitis B (n=5, including 2 chronic) or C (n=10) infection were identified. Eight patients received prior/concomitant anti-tumor necrosis factor-alpha therapy; NR n=2. 51 AEs (n=13 serious [non-fatal]; n=38 non-serious) were reported, reflecting the general VDZ safety profile in patients without viral hepatitis. Liver-related events were reported in two patients with hepatitis C: one patient who was a smoker reported hepatic neoplasm; the other reported hepatic mass and had a history of skin cancer, cholecystectomy, bladder tumor removal, and right radical orchidectomy. Of events with a reported outcome, 22/26 (84.6%) were resolved/resolving and 4/26 (15.4%) were unresolved at the time of reporting; NR n=25. VDZ was continued in 10/14 (71.4%) patients and discontinued in 4/14 (28.6%); NR n=1. Conclusion: There was no evidence of increased risk of viral reactivation in patients with hepatitis B or C receiving VDZ. Limitations associated with post-marketing safety reporting and currently limited availability of VDZ in regions with endemic hepatitis B and C should be considered when interpreting these results.

Prospective comparison of preference and efficacy of adalimumab and infliximab for treating ulcerative colitis naive to antitumor necrosis factor therapy.

There have been few reports on 2 tumor necrosis factor alpha inhibitors, infliximab and adalimumab, with respect to patient preference and efficacy in ulcerative colitis (UC).We used questionnaires to evaluate the preference and reasons for drug choice between infliximab and adalimumab in UC patients naive to antitumor necrosis factor alpha therapy. We also analyzed the efficacy of infliximab and adalimumab prospectively and endoscopically before treatment and at 14 and 54 weeks.Of the 25 UC patients, infliximab and adalimumab were chosen by 10 (40%) and 15 (60%), respectively. Patients who favored infliximab considered “fear of syringes” (7/10, 70%) as the most important influencing factor, whereas patients who favored adalimumab considered “ease of administration” (10/15, 66.7%) and “time required for therapy” (10/15, 66.7%) as the most important factors. There were no statistical differences in remission induction and maintenance between the infliximab and adalimumab groups with regard to response, remission, mucosal healing, steroid-free, and steroid-free remission rates at weeks 14 and 54.The efficacy of adalimumab in remission induction and maintenance was equivalent to that of infliximab in UC patients naive to antitumor necrosis factor alpha therapy in this prospective study, but more patients preferred adalimumab.

Endoscopic Recurrence 6 Months After Ileocecal Resection in Children With Crohn Disease Treated With Azathioprine

Intestinal surgery is an important part of Crohn disease (CD) treatment in children. The aim of the present study was to compare the rate of endoscopic recurrence at the sixth month after ileocecal resection (ICR) in children with CD treated with azathioprine between patients who received prior antitumor necrosis factor alpha (anti-TNF-α) therapy and those who were not administered this therapy. Moreover, we tried to identify the potential risk factors for disease recurrence and describe the schedule of long-term follow-up after surgery. We prospectively collected data from pediatric patients with CD, who underwent ICR between October 2011 and June 2015 at our hospital and were treated with azathioprine monotherapy after ICR. We evaluated the endoscopic recurrence (Rutgeerts score) at the sixth month after ICR in all included patients. Among 21 included patients, 13 achieved endoscopic remission (Rutgeerts score < i2) at the sixth month after ICR. No difference was found between patients who received prior anti-TNF-α therapy and those who did not. We did not find any clinically relevant factors associated with endoscopic recurrence rate at the sixth month. Prior anti-TNF-α therapy does not seem to be a strong risk factor for endoscopic recurrence within 6 months after ICR. Further studies on large sample of patients are needed to identify potential predictors of disease recurrence.

Coexistence of multiple sclerosis and ankylosing spondylitis: Report of four cases from Russia and review of the literature

Multiple sclerosis is a chronic demyelinating disorder of the central nervous system. There are many cases of multiple sclerosis – like syndrome and demyelinating disorders in systemic lupus erythematosus, Sjogren disease, Behcet disease and other autoimmune conditions. Coexistence of ankylosing spondylitis and multiple sclerosis usually is rare but in this article we report 4 Russian patients with concomitant multiple sclerosis and ankylosing spondylitis diseases. None of these patients received anti-tumor necrosis factor alpha therapy prior to diagnosis of multiple sclerosis. Pathogenesis, diagnostic and treatment challenges are discussed.

Paradoxical Inflammation in IBD Patients Treated with Anti-Tumor Necrosis Factor Alpha Therapy

Paradoxical Inflammation in IBD Patients Treated with Anti-Tumor Necrosis Factor Alpha Therapy

Anti-tumor necrosis factor alpha therapy, Adalimumab, in Rasmussen's encephalitis

Anti-tumor necrosis factor alpha therapy, Adalimumab, in Rasmussen's encephalitis

Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related Cytokines.

Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated. Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells. Digoxin or a vehicle was injected into mice with colitis intraperitoneally every other day and changes in body weight were evaluated. After 6 to 8 weeks, the treated mice were killed and evaluated for histological score, T-cell subset, and cytokine messenger RNA (mRNA) expression in the colonic tissue. Wasting disease and histological damage were significantly attenuated in digoxin-treated mice with colitis compared with those in the vehicle-treated mice. In addition, the mRNAs of Th17-related cytokines were downregulated, whereas those of interleukin-10 were upregulated in the colonic mucosa of digoxin-treated mice. However, unexpectedly, the mRNA expression level of tumor necrosis factor alpha did not decrease in the colonic mucosa of digoxin-treated mice with colitis. This observation suggests that digoxin may ameliorate colitis by a tumor necrosis factor alpha-independent pathway. This study has shown for the first time that treatment with digoxin can ameliorate murine experimental colitis. This finding suggests that the suppression of Th17 using reagents such as digoxin could be effective in treating Crohn's disease refractory to anti-tumor necrosis factor alpha therapy.

Anti-TNFα Treatment After Surgical Resection for Crohnʼs Disease Is Effective Despite Previous Pharmacodynamic Failure

The outcome of patients with Crohn's disease who failed anti-tumor necrosis factor alpha (anti-TNFα) therapy despite adequate serum drug levels (pharmacodynamic failure) is unclear. We aimed to assess such pediatric patients who underwent intestinal resection and were re-treated with the same anti-TNFα agent postoperatively. Pediatric patients with Crohn's disease who underwent intestinal resection and were treated with anti-TNFα agents postoperatively were assessed retrospectively. Patients were stratified to those with preoperative anti-TNFα pharmacodynamic failure and those with no preoperative anti-TNFα treatment. A total of 53 children were included, 18 with pharmacodynamic failure and 35 controls. Median age at intestinal resection was 14.8 years with 23 (43%) girls. The median time from intestinal resection to anti-TNFα initiation was 8 months (interquartile range 4-14 months). At the time of postoperative anti-TNFα initiation there were no differences in clinical, laboratory, and anthropometric measures between groups. Similar proportions of patients from both groups were in clinical remission on anti-TNFα treatment after 12 months and at the end of follow-up (1.8 years, interquartile range, 1-2.9 years): 89% versus 88.5% and 83% versus 80% for pharmacodynamic failure patients and controls, respectively; P = 0.9. No significant differences were observed at 14 weeks and 12 months of postoperative anti-TNFα treatment including endoscopic remission rate and fecal calprotectin. Both groups significantly improved all measures during postoperative anti-TNFα treatment. Pediatric patients with Crohn's disease who failed anti-TNFα therapy despite adequate drug levels and underwent intestinal resection can be re-treated with the same agent for postoperative recurrence with high success rate similar to that of anti-TNFα naive patients.

Defining the ultrasound longitudinal natural history of newly diagnosed pediatric small bowel Crohn disease treated with infliximab and infliximab-azathioprine combination therapy.

Little is known about changes in the imaging appearances of the bowel and mesentery over time in either pediatric or adult patients with newly diagnosed small bowel Crohn disease treated with anti-tumor necrosis factor-alpha (anti-TNF-α) therapy. To define how bowel ultrasound findings change over time and correlate with laboratory inflammatory markers in children who have been newly diagnosed with pediatric small bowel Crohn disease and treated with infliximab. We included 28 pediatric patients treated with infliximab for newly diagnosed ileal Crohn disease who underwent bowel sonography prior to medical therapy and at approximately 2weeks, 1month, 3months and 6months after treatment initiation; these patients also had laboratory testing at baseline, 1month and 6months. We used linear mixed models to compare mean results between visits and evaluate whether ultrasound measurements changed over time. We used Spearman rank correlation to assess bivariate relationships. Mean subject age was 15.3±2.2years; 11 subjects were girls (39%). We observed decreases in mean length of disease involvement (12.0±5.4 vs. 9.1±5.3cm, P=0.02), maximum bowel wall thickness (5.6±1.8 vs. 4.7±1.7mm, P=0.02), bowel wall color Doppler signal (1.7±0.9 vs. 1.2±0.8, P=0.002) and mesenteric color Doppler signal (1.1±0.9 vs. 0.6±0.6, P=0.005) at approximately 2weeks following the initiation of infliximab compared to baseline. All laboratory inflammatory markers decreased at 1month (P-values<0.0001). There was strong correlation between bowel wall color Doppler signal and fecal calprotectin (ρ=0.710; P<0.0001). Linear mixed models confirmed that maximum bowel wall thickness (P=0.04), length of disease involvement (P=0.0002) and bowel wall color Doppler signal (P<0.0001) change over time in response to infliximab, when adjusted for age, sex, azathioprine therapy, scanning radiologist and baseline short pediatric Crohn's disease activity index score. The ultrasound appearance of the bowel changes as early as 2weeks after the initiation of infliximab therapy. There is strong correlation between bowel wall color Doppler signal and fecal calprotectin.

Anti-rheumatic treatment is not associated with reduction of pentraxin 3 in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

BackgroundPentraxin 3 is proposed to be a marker of inflammation and cardiovascular risk, but its role in inflammatory rheumatic diseases (IRDs) is still uncertain. Therefore, we wanted to examine if anti-rheumatic treatment reduced serum PTX3 (s-PTX3) levels in IRDs, and if s-PTX3 levels were related to other markers of inflammation and to endothelial function (EF).MethodsWe examined s-PTX3, EF and established inflammatory biomarkers in 114 IRD patients from the PSARA study before and after 6 weeks and 6 months of treatment with methotrexate (MTX) or anti-tumor necrosis factor alpha (anti-TNF) therapy with or without MTX co-medication.Resultss-PTX3 levels in all IRD diagnoses were above the upper limit of the reference range. In contrast to established inflammatory markers, in particular CRP and ESR, s-PTX3 levels did not change significantly after 6 weeks and 6 months of anti-rheumatic therapy. There was no difference in change in s-PTX3 levels from baseline to 6 weeks and 6 months between MTX monotherapy and anti-TNF regimens. CRP, ESR and EF were not related to changes in s-PTX3 neither in crude nor adjusted analyses.ConclusionIRD patients have increased s-PTX3 levels, which, in contrast to other inflammatory markers, do not seem to improve within 6 months of therapy with MTX and/or anti-TNF. Thus, s-PTX3 might reflect a persisting immune process, even a causal factor of inflammation, not inhibited by the standard anti-rheumatic treatment. Furthermore, even though s-PTX3 is thought to be a strong predictor of cardiovascular prognosis, it was not related to EF.

P548 Hepatitis B virus reactivation in hepatitis B virus infected patients with inflammatory bowel disease receiving anti-tumor necrosis factor-alpha therapy

Background: Reactivation of hepatitis B virus (HBV) is one of the most important side effects in IBD patients with HBV infection treated with anti-TNF-alpha agents. We investigated the rate of prophylaxis and the risk of HBV reactivation in HBV infected patients with IBD receiving anti-TNF-alpha therapy. Methods: This was a retrospective multicenter study including 14 academic teaching hospitals in Korea. IBD patients with HBV infection (HBsAg-positive) who treated with anti-TNF-alpha agents were enrolled. Medical records of patients were reviewed and data were collected using web-based case report form. Results: A total of 61 patients (18 UC, 43 CD) were included. 70% were male and mean age at diagnosis was 34.9±12.0 years. Indications for anti-TNF-alpha therapy were steroid-dependency, refractoriness to conventional therapies, or fistulizing disease. Among 43 patients who tested serum HBV-DNA levels, 35 (81%) were positive for HBV-DNA prior to anti-TNF-alpha therapy. Only half of the patients (51%) received prophylactic anti-viral agents. During the follow-up of median 24 months, 16.4% of patients experienced HBV reactivation, of which 6 patients (60%) were taking concomitant azathioprine. Median duration of anti-TNF-alpha therapy before HBV reactivation was 9 months. HBV reactivation was managed by change or adding of anti-viral agents in 6 patients, discontinuing ant-TNF-alpha in 1 patient, and combination of both in 2 patients, achieving virological response in most patients (90%). HBV reactivation was more frequent in non-prophylaxis group than prophylaxis group (10% vs 24.1%, p=0.15). No other predictors for HBV reactivation were identified. There was no difference in the rates of IBD flare, IBD-related surgery or hospitalization between two groups. Conclusions: HBV reactivation was not infrequent in HBsAg-positive IBD patients treated with anti-TNF-alpha agents. Prophylaxis for HBV reactivation and careful monitoring should be performed for such patients.

Effect of anti-tumor necrosis factor alpha therapy on bone health and biomarkers of bone turnover in Indian patients with ankylosing spondylitis

Background: We evaluated the relationship between bone mineral density (BMD) and biomarkers of bone turnover in ankylosing spondylitis (AS) patients treated with anti-tumor necrosis factor alpha (TNF-α) agents. Methods: Fifty-one AS patients were screened, of which 27 were started on anti-TNF therapy in accordance to the assessment of AS guidelines. Detailed assessments of erythrocyte sedimentation ratio (ESR), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrological index (BASMI), AS disease activity score-ESR, and AS quality of life (AsQOL) questionnaire were done at baseline and 6 months. Vitamin D, parathyroid hormone, and osteocalcin were measured along with BMD of the lumbar spine, anteroposterior (AP) and lateral view, and hip. Results: Out of 27 patients, 12 patients had osteoporosis. At 6 months, significant improvements were seen for BASDAI (mean 2.33 ± 1.08, P Conclusion: Anti-TNF-α has a beneficial effect on bone metabolism resulting in improved bone formation.

Role of 18F-fluorodeoxyglucose Positron Emission Tomography in the Monitoring of Inflammatory Activity in Crohnʼs Disease

Fluorine-fluorodeoxyglucose positron emission tomography (F-FDG PET) has recently attracted interest for the measurement of disease activity in Crohn's disease (CD). The aim of this study was to assess the utility of FDG-PET as a marker of progression of inflammatory activity and its response to treatment in patients with CD. Twenty-two patients with active CD were recruited prospectively to undergo FDG-PET scanning at 2 time points. All 22 index scans were used to assess sensitivity and specificity against a reference standard magnetic resonance imaging measure. Correlations with clinicopathological markers of severity (Harvey-Bradshaw Index, C-reactive protein, and calprotectin) were also performed. Of note, 17/22 patients participated in the longitudinal component and underwent scanning before and 12 weeks after the initiation of anti-tumor necrosis factor alpha therapy. Patients were subcategorized on the basis of a clinically significant response, and responsiveness of the PET measures was assessed using previously described indices. Of note, 5/22 patients took part in the test-retest component of the study and underwent scanning twice within a target interval of 1 week, to assess the reproducibility of the PET measures. The sensitivity and specificity of F-FDG PET were 88% and 70%, respectively. Standardized uptake value (SUV)-related PET measures correlated significantly both with C-reactive protein and Harvey-Bradshaw Index in cross-sectional and longitudinal analyses. (G)SUVMAX and (G)SUVMEAN demonstrated favorable responsiveness and reliability characteristics (responsiveness ratio of Guyatt >0.80 and % variability <20%) compared with volume-dependent FDG-PET measures. A proportion of the FDG signal (10%-30%) was found to originate from the lumen of diseased segments. F-FDG PET may be useful for longitudinal monitoring of inflammatory activity in CD.

Impact of Anti-Tumor Necrosis Factor Alpha Therapy on Postoperative Outcomes in the Surgical Management of Crohn’s Disease

Kulaylat, Afif N. MD; Kulaylat, Audrey S. MD; Schaefer, Eric W.; Tinsley, Andrew MD; Williams, Emmanuelle D. MD; Koltun, Walter A. MD, FACS, FASCRS; Hollenbeak, Christopher S. PhD; Messaris, Evangelos MD, PhD, FACS, FASCRS Author Information

Multicenter Experience With Mycophenolate Mofetil in Cardiac Sarcoidosis

SESSION TITLE: Sarcoidosis SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, October 26, 2016 at 07:30 AM - 08:30 AM PURPOSE: Cardiac sarcoidosis (CS) is a potentially life-threatening cardiomyopathy, although limited data exist to guide pharmacotherapy. Corticosteroids presently constitute the mainstay of treatment, but are associated with significant toxicities. Mycophenolate mofetil (MMF) is a corticosteroid-sparing agent that may have a role in management of CS. METHODS: Detailed retrospective chart review was performed to identify patients from two academic medical centers meeting 2014 Heart Rhythm Society Expert Consensus criteria for the diagnosis of CS, from 1994-2014. Patients receiving MMF for CS were included in this analysis. Data regarding demographics, disease characteristics, concurrent therapies, and composite endpoint of ventricular assist device (VAD), heart transplant, or death, were abstracted. Kaplan-Meier analyses were used to evaluate time-dependent variables. RESULTS: A total of 33 patients were treated with MMF for a median of 22.0 months (IQR13.0-104.0). Median age at diagnosis was 51.0 years (IQR 47.0-58.0), 24 (73%) patients were male, and 26 (79%) were Caucasian. Cardiomyopathy with left ventricular ejection fraction (LVEF) <40% was the most common presenting manifestation, affecting 17 (52%) patients, followed by 12 (36%) with atrioventricular block, and 11 (33%) with ventricular arrhythmia; 6 (18%) had more than one of these at presentation. Only 3 (9%) patients had isolated cardiac involvement by sarcoidosis, while 28 (85%) also had pulmonary involvement. All but one patient (97%) initially received concurrent prednisone, 2 (6%) received concurrent anti-tumor necrosis factor-alpha therapy, and 1 (3%) received concurrent cyclosporine. Twenty (of 32, 63%) patients were tapered off prednisone, with median prednisone duration after MMF initiation of 15.0 months (IQR 7.1-33.5). Median time to worsening cardiomyopathy (clinical and/or 10% decrease in LVEF) was 28.0 months, while time to recurrent ventricular arrhythmia was 11.5 months. Six (18%) patients received a VAD, and 5 (15%) underwent transplantation (4 with preceding VAD). After MMF initiation, median time to the composite endpoint of VAD, heart transplant, or death, was 79.0 months. Three (9%) patients not receiving VAD or transplant changed therapy for apparent disease progression. Four (12%) patients stopped MMF due to adverse effects, including cytopenias (3), rash (1), and tremor (1). CONCLUSIONS: In this multicenter analysis, MMF allowed a majority of patients with CS to be weaned off prednisone. Median survival without the composite endpoint of VAD, transplant, or death, was more than 6.5 years, suggesting a benefit of immunosuppression. Discontinuation of MMF for toxicity was uncommon. CLINICAL IMPLICATIONS: Prospective studies are needed to better define the role of MMF in CS therapy. DISCLOSURE: The following authors have nothing to disclose: Lynn Fussner, Erin Karlstedt, Nowell Fine, Sanjay Kalra, Eva Carmona, James Utz, Debra Isaac, Leslie Cooper No Product/Research Disclosure Information

The evaluation of sleep quality and response to anti-tumor necrosis factor α therapy in rheumatoid arthritis patients.

Poor sleep quality (SQ) is increasingly recognized as giving rise to decreased quality of life, and raising pain perception. Our aim is to evaluate the SQ in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor alpha (anti-TNF-α) therapy. This was a prospective observational and open-label study of RA patients. A total of 35 patients with RA were enrolled in this study. Of the 35 patients, 22 had high disease activity (DA), and 13 were in remission. High DA group was initiated an anti TNF-α therapy. Clinical and objective parameters of SQ were assessed by using the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG). The total PSQI score and the frequency of poor SQ were high in 60% of the RA patients. The median PSQI score was significantly higher in the high DA group than in the remission group (P=0.026). Following an anti-TNF-α therapy initiation, significant improvements were observed in the high DA group by PSQI test (P=0.012). However, no statistically significant difference was found by PSG (P>0.05). Although an improvement in DA with anti-TNF-alpha therapy did not provide an amelioration in laboratory parameters, we found a significant improvement in SQ by subjective PSQI test. These findings may support that sleep disorders in RA are likely to be associated with a complex pathophysiology.