Subsequent Flares Research Articles

Serum viral load at the virological relapse predicts subsequent clinical flares in chronic hepatitis B patients off entecavir therapy.

Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy, but the risk of subsequent clinical outcome remains unclear and unpredictable. We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy. This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg-negative and viral DNA-undetectable when discontinuing entecavir after at least 3years on therapy. Following virological relapse (viral DNA >2,000IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis. The cumulative incidence of clinical hepatitis 2years after virological relapse was 61.0% (95% confidence interval [CI], 49.9-72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9-66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio [HR], 1.31 per log IU/mL; 95% CI, 1.07-1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27-2.10), after adjustment for serum aminotransferase and alfa-fetoprotein levels in the multivariate analysis. Viral DNA >100000IU/mL predicted a nearly inevitable occurrence of clinical flare (P<0.0001). A high viral load at the virological relapse predicts subsequent clinical hepatitis in CHB patients who discontinue entecavir.

Increased Cell Adhesion Molecules, PECAM-1, ICAM-3, or VCAM-1, Predict Increased Risk for Flare in Patients With Quiescent Inflammatory Bowel Disease.

Predicting the risk of flare-ups for patients with inflammatory bowel disease (IBD) is difficult. Alterations in gut endothelial regulation of mucosal immune homeostasis might be early events leading to flares in IBD. Cell adhesion molecules (CAMs), in particular, are important in maintaining endothelial integrity and regulating the migration of leukocytes into the gut. We evaluated the mRNA expression of various tight junction proteins, with an emphasis on CAMs, in 40 patients with IBD in clinical remission. Patients were retrospectively assessed at 6, 12, and 24 months after baseline colonoscopy, and at the end of all available follow-up (maximum 65 mo), for flare events to determine whether baseline mRNA expression was associated with subsequent flares. At all follow-up points, the baseline expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), ICAM-3, and VCAM-1 was significantly higher in patients who flared than in those who did not (2.4-fold elevation, P=0.012 for PECAM-1; 1.9-fold increased, P=0.03 for ICAM-3; and 1.4-fold increased, P=0.02 for VCAM-1). PECAM-1 and ICAM-3 expression was significantly increased in patients who flared as early as 6 months after baseline colonoscopy. In contrast, there were no significant differences between patients with and without flares in baseline expression of other CAMs (ESAM, ICAM-1, ICAM-2, E-selectin, P-selectin, and MadCAM1). Increased expression of PECAM-1, ICAM-3, and VCAM-1 in colonic biopsies from patients with IBD in clinical remission is associated with subsequent flares. This suggests that increases in the expression of these proteins may be early events that lead to flares in patients with IBD.

Dual-energy computed tomography as a diagnostic tool for gout during intercritical periods.

The aim of this study is to evaluate the diagnostic yield of dual-energy computed tomography (DECT) in detection of uric acid accumulation in joints or periarticular structures in patients suspected of having gout, in their intercritical period. Patients with a history of recurrent, short-lived mono- or oligo-arthralgia or arthritis, referred to the rheumatology clinic for diagnosis of their condition, were included in this retrospective evaluation. DECT confirmed the diagnosis of gout in 30 of 50 patients (60%). A positive DECT was present in 12 of 16 cases (75%) with serum uric acid > 8.5 mg/dL, compared to seven of 13 cases (54%) and two of five cases (40%) with levels of 6.1-8.5 mg/dL and ≤ 6 mg/dL, respectively. The diagnostic impact of screening hands and feet were highest (78% and 56%, respectively). Follow-up data were available for 24 of the 30 patients with urate deposits identified by DECT. Twenty-one were treated with urate-lowering agents, all responded with lowering of serum uric acid and cessation of flares. Follow-up data were available for 16 of the 20 patients with no urate deposits identified by DECT. Gout was diagnosed in two of them by synovial fluid examination during subsequent flares. Both positive and negative predictive values of DECT for diagnosing gout in this patient population were 87%. Following DECT, treatment regimen was modified to gout-specific therapy in 52% of the patients. The ability to make a definite diagnosis of gout by DECT imaging in a substantial number of asymptomatic patients in the intercritical period should help in treatment decision-making and improve patient adherence to long-term urate-lowering therapy.

High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT): A multicenter randomized clinical trial.

Objectives:To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA).Methods:In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought.Results:A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy.Conclusions:Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent flares. Leflunomide is a good maintenance treatment as single treatment.

Circularization of tidally disrupted stars around spinning supermassive black holes

We study the circularization of tidally disrupted stars on bound orbits around spinning supermassive black holes by performing three-dimensional smoothed particle hydrodynamic simulations with Post-Newtonian corrections. Our simulations reveal that debris circularization depends sensitively on the efficiency of radiative cooling. There are two stages in debris circularization if radiative cooling is inefficient: first, the stellar debris streams self-intersect due to relativistic apsidal precession; shocks at the intersection points thermalize orbital energy and the debris forms a geometrically thick, ring-like structure around the black hole. The ring rapidly spreads via viscous diffusion, leading to the formation of a geometrically thick accretion disk. In contrast, if radiative cooling is efficient, the stellar debris circularizes due to self-intersection shocks and forms a geometrically thin ring-like structure. In this case, the dissipated energy can be emitted during debris circularization as a precursor to the subsequent tidal disruption flare. The possible radiated energy is up to ~2*10^{52} erg for a 1 Msun star orbiting a 10^6 Msun black hole. We also find that a retrograde (prograde) black hole spin causes the shock-induced circularization timescale to be shorter (longer) than that of a non-spinning black hole in both cooling cases. The circularization timescale is remarkably long in the radiatively efficient cooling case, and is also sensitive to black hole spin. Specifically, Lense-Thirring torques cause dynamically important nodal precession, which significantly delays debris circularization. On the other hand, nodal precession is too slow to produce observable signatures in the radiatively inefficient case. We also discuss the relationship between our simulations and the parabolic TDEs that are characteristic of most stellar tidal disruptions.

Update on Biologic Therapies for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible.

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus.

Background/PurposeA slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE.MethodsWe prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score.ResultsSeventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2.ConclusionIV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.

THE ROLE OF ERUPTING SIGMOID IN TRIGGERING A FLARE WITH PARALLEL AND LARGE-SCALE QUASI-CIRCULAR RIBBONS

In this paper, we present observations and analysis of an interesting sigmoid formation, eruption and the associated flare that occurred on 2014 April 18 using multi-wavelength data sets. We discuss the possible role of the sigmoid eruption in triggering the flare, which consists of two different set of ribbons: parallel ribbons as well as a large-scale quasi-circular ribbon. Several observational evidence and nonlinear force-free field extrapolation results show the existence of a large-scale fan-spine type magnetic configuration with a sigmoid lying under a section of the fan dome. The event can be explained with the following two phases. During the pre-flare phase, we observed the formation and appearance of sigmoid via tether-cutting reconnection between the two sets of sheared fields under the fan dome. The second, main flare phase, features the eruption of the sigmoid, the subsequent flare with parallel ribbons, and a quasi-circular ribbon. We propose the following multi-stage successive reconnections scenario for the main flare. First, tether-cutting reconnection is responsible for the formation and the eruption of the sigmoid structure. Second, the reconnection occurred in the wake of the erupting sigmoid produces the parallel flare ribbons on the both sides of the circular polarity inversion line. Third, the null-type reconnection higher in the corona, possibly triggered by the erupting sigmoid, leads to the formation of a large quasi-circular ribbon. For the first time we suggest a mechanism for this type of flare consisting of a double set of ribbons triggered by an erupting sigmoid in a large scale fan-spine type magnetic configuration.

Subclinical synovitis detected by macrophage PET, but not MRI, is related to short-term flare of clinical disease activity in early RA patients: an exploratory study.

IntroductionResidual subclinical synovitis can still be present in joints of rheumatoid arthritis (RA) patients despite clinical remission and has been linked to ongoing radiological damage. The aim of the present study was to assess subclinical synovitis by positron emission tomography (PET; macrophage tracer 11C-(R)-PK11195) in early RA patients with minimal disease activity without clinically apparent synovitis (MDA); and its relationship with clinical outcome and magnetic resonance imaging (MRI), respectively.MethodsBaseline PET and MRI of hands/wrists were performed in 25 early MDA RA patients (DAS 44 < 1.6; no tender/swollen joints) on combined DMARD therapy. PET tracer uptake (semi-quantitative score: 0–3) and MRI synovitis and bone marrow edema (OMERACT RAMRIS) were assessed in MCP, PIP and wrist joints (22 joints/patient; cumulative score).ResultsEleven of 25 patients (44 %) showed enhanced tracer uptake in ≥ 1 joint. Fourteen of these 25 (56 %) patients developed a flare within 1 year: 8/11 (73 %) with a positive, and 6/14 (43 %) with a negative PET. In the latter, in 5/6 patients flare was located outside the scan region. Median cumulative PET scores of patients with a subsequent flare in the hands or wrists were significantly higher than those of patients without a flare (1.5 [IQR 0.8–5.3] vs 0.0 [IQR 0.0–1.0], p = 0.04); significance was lost when all flares were considered (1.0 [IQR 0.0–4.0] vs 0.0 [IQR 0.0–1.0], p = 0.10). No difference in cumulative MRI scores was observed between both groups.ConclusionsPositive PET scans were found in almost half of early RA patients with MDA. Patients with a subsequent flare in hand or wrist had higher cumulative PET scores but not MRI scores, suggesting that subclinical arthritis on PET may predict clinical flare in follow-up.

Staphylococcus Aureus carriage and long-term Rituximab treatment for Granulomatosis with polyangiitis.

Objective. Chronic nasal carriage of Staphylococcus aureus (SA) increases the risk of relapse while Rituximab (RTX) is an effective agent for inducing and maintaining remission in patients with Granulomatosis with polyangiitis (GPA). We investigated whether B cell depletion and hypogammaglobulinemia that occur during RTX treatment increase the risk of chronic SA nasal carriage and subsequent disease flares, in GPA patients on long-term RTX maintenance therapy.Methods. Retrospective cohort study from a disease registry involving 29 GPA patients receiving RTX maintenance (median RTX dose of 9 g) during a median period of 49 months. Nasal swabs were collected prior and during RTX for a median of 3 and 9 swabs respectively. Persistent SA nasal carriage was defined with the presence of SA in more than 75% of nasal swabs.Results. SA nasal carriage did not change during RTX (p = 0.297). However, the rate of positive nasal swabs in GPA patients with transient SA nasal carriage during RTX maintenance increased from 0 prior RTX to 0.42 during RTX (p = 0.017). Persistent SA nasal carriage did not increase the risk of relapses (p = 0.844), of hypogammaglobulinemia (p = 0.122) and of severe infections (p = 0.144), but reduced the risk of chronic infections (p = 0.044). Change in SA carriage status during RTX did not influence the risk of relapses (p = 0.756), hypogammaglobulinamia (p = 0.474) and infections, either severe (p = 0.913) or chronic (p = 0.121).Conclusion. Long-term RTX maintenance therapy in GPA patients did not significantly influence SA nasal carriage status. Persistent SA carriage during long-term RTX treatment did not seem to increase the risk of relapses, but seemed to decrease the risk of hypogammaglobulinemia associated chronic infections.

Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study

ObjectiveTo assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission.MethodsACT-RAY...

THE PECULIAR RADIO-LOUD NARROW LINE SEYFERT 1 GALAXY 1H 0323+342

We present a multi-wavelength study of the radio-loud narrow line Seyfert 1 galaxy (NLSy1), 1H 0323+342, detected by Fermi Gamma Ray Space Telescope. Multi-band light curves show many orphan X-ray and optical flares having no corresponding {\gamma}-ray counterparts. Such anomalous variability behavior can be due to different locations of the emission region from the central source. During a large flare, {\gamma}-ray flux doubling time scale as small as $\sim$ 3 hours is noticed. We built spectral energy distribution (SED) during different activity states and modeled them using an one-zone leptonic model. The shape of the optical/UV component of the SEDs is dominated by accretion disk emission in all the activity states. In the X-ray band, significant thermal emission from the hot corona is inferred during quiescent and first flaring states, however, during subsequent flares, non-thermal jet component dominates. The {\gamma}-ray emission in all the states can be well explained by inverse-Compton scattering of accretion disk photons reprocessed by the broad line region. The source showed violent intra-night optical variability, coinciding with one of the high {\gamma}-ray activity states. An analysis of the overall X-ray spectrum fitted with an absorbed power-law plus relativistic reflection component hints for the presence of Fe K-{\alpha} line and returns a high black hole spin value of a=0.96 $\pm$ 0.14. We argue that 1H 0323+342 possesses dual characteristics, akin to flat spectrum radio quasars (FSRQs) as well as radio-quiet NLSy1s, though at a low jet power regime compared to powerful FSRQs.

SAT0255 Clinical and Radiographic Outcomes at 2 Years and the Effect of TOCILIZUMAB Discontinuation following Sustained Remission in the Second and Third Year of the ACT-RAY Study

BackgroundIn ACT-RAY, MTX-IR patients (pts) with moderate to severe RA were randomized to either an add-on (tocilizumab [TCZ]+MTX) or a switch (TCZ+placebo [PBO]) strategy. Data at 24 and 52 weeks...

Sorafenib Treatment Following Hematopoietic Stem Cell Transplant In Pediatric FLT3/ITD+ AML

Internal tandem duplications of the FLT3 gene (FLT3/ITD) portend poor outcome in both adult and pediatric AML and hematopoietic stem cell transplantation (HSCT) is often performed. Unfortunately, approximately 35% of patients will have disease recurrence despite HSCT and curative options are limited in that context. Sorafenib is an oral multi-target tyrosine kinase with demonstrable efficacy in this AML subtype. Moreover, retrospective studies in adults with FLT3/ITD+ AML suggest tolerability and potential clinical benefit of sorafenib when used in the post HSCT setting for treatment of early relapse or minimal residual disease (MRD) emergence. There is limited published data regarding sorafenib's tolerability and efficacy following HSCT in pediatric FLT3/ITD+ AML. We report here a retrospective review of our experience.We conducted a retrospective study of pediatric FLT3/ITD+ patients treated with allogeneic HSCT followed by sorafenib in the first 18 months following HSCT. Between March 2008 and March 2012, 13 FLT3/ITD+ pediatric patients at 7 HSCT centers met criteria for study inclusion. Median age at time of treatment was 14 years (range 6-21 years) and 6/14 (46%) were male. 9 patients underwent matched family donor HSCT and 4 had a matched unrelated donor. Sorafenib was initiated early after HSCT (median: 66 days, range 44-170 days) as prophylaxis in 5 patients who were considered to have very high risk features including failure to achieve clinical remission (CR) following first course of chemotherapy (N=2), high allelic ratio FLT3/ITD at diagnosis (N=1) and MRD at time of HSCT (N=2). For the remainder, sorafenib was given after sign of relapse (MRD or morphologic) at a median of 90 days (range 45-480 days) following HSCT. 11/13 patients received single agent therapy; 2 patients with morphologic relapse received additional chemotherapy (N=1) or radiotherapy (N=1).Among the entire group, post HSCT sorafenib therapy was initiated a median of 80 days following HSCT (range 44-480 days) at a median dose of 150 mg/m2/day (range 75-340 mg/m2/day) and continued for a median of 12 months (range 0.5-52 months). 9/13 patients (69%) experienced toxicity which was felt to be medically significant including thrombocytopenia (N=2), rash (N=3), anorexia (N=1), myelosuppression (N=3), infection (N=2) and life threatening cardiac dysfunction (N=1 in patient treated concomitantly with mitoxantrone). In 8/13 cases (61%) the toxicity resulted in reduction or temporary discontinuation of sorafenib yet all patients tolerated retrial of drug at the same or reduced dosing. One additional patient experienced dose limiting marrow hypoplasia at dosing of 340 mg/m2/day. Sorafenib did not appear to exacerbate GVHD. 8/13 (62%) patients had controlled GHVD at time of sorafenib initiation and only 2 patients had subsequent skin flare that was temporally associated with wean of immune suppression and did not preclude use of further sorafenib.Overall, 10/13 (77%) patients remain alive and 7/13 (54%) are disease free. Of 7 patients in continued CR, the median survival is 3.6 years from HSCT (range 1.75-5.6 years); 6/7 are off sorafenib therapy for a median of 10.5 months (range 7-36 months) after receiving treatment for a median of 19 months (range 8-52 months). 6/13 patients (46%) experienced progressive or recurrent disease while on therapy, 3 of whom have died: 2 from rapid disease progression despite sorafenib initiation and 1 from wild-type FLT3 recurrence. 3 additional patients with recurrent disease are receiving salvage therapy, 1 of whom has achieved a 2nd CR. Of particular interest is the outcome of patients who received sorafenib for MRD in the peri transplant period. All 5 remain alive and disease-free a median of 3.6 years from HSCT (range 1.75-5.6 years) and have been off sorafenib for a median of 12 months (range 7-36 months). Conversely, of the 5 patients who started treatment for morphologic recurrence, only 1/5 (20%) remain in CR. Of 3 additional patients who received prophylactic treatment for high AR or poor induction response, 2/3 have recurred, 1 of whom is now in 2ndCR with higher dose sorafenib in combination with conventional chemotherapy.Our study suggests that sorafenib is tolerable and may improve survival for pediatric patients who undergo HSCT for FLT3/ITD+ AML. Prospective study is necessary to further confirm tolerability and to determine the scope of clinical benefit for this high risk population. Disclosures:Off Label Use: Sorafenib use in AML will be discussed.

Recommendations for pimecrolimus 1% cream in the treatment of mild-to-moderate atopic dermatitis: from medical needs to a new treatment algorithm

Pimecrolimus 1% cream is an effective, non-corticosteroid, topical anti-inflammatory treatment for atopic dermatitis (AD). The aim of this article was to review published clinical data that have examined how pimecrolimus can address the medical needs of AD patients. Clinical studies have demonstrated that early treatment with pimecrolimus decreases the progression to disease flares, rapidly improves pruritus and significantly enhances quality of life. Patients find the formulation easy to apply, which may result in improved adherence with the treatment regimen. Pimecrolimus, in contrast to topical corticosteroids (TCSs), does not induce skin atrophy or epidermal barrier dysfunction and is highly effective for the treatment of AD in sensitive skin areas. Furthermore, pimecrolimus reduces the incidence of skin infections compared with TCSs and is not associated with other TCS-related side effects such as striae, telangiectasia and hypothalamic-pituitary-adrenal axis suppression. An additional benefit of pimecrolimus is its substantial steroid sparing effect. On the basis of these data, a new treatment algorithm for patients with mild-to-moderate AD is proposed in which pimecrolimus is recommended as a first line therapy for patients with established mild AD at the first signs and symptoms of disease. Pimecrolimus is also recommended for mild-to-moderate AD after initial treatment with a TCS. After resolution of lesions, maintenance treatment with pimecrolimus may effectively prevent subsequent disease flares. In conclusion, the clinical profile of pimecrolimus suggests that it may be considered the drug of choice for the treatment of mild-to-moderate AD in children as well as adults and particularly in sensitive skin areas.

Limited Risks of Major Congenital Anomalies in Children of Mothers With IBD and Effects of Medications

Concerns persist about the risk of major congenital anomalies in children of women with inflammatory bowel disease (IBD), and whether medication use affects risk. We assessed these risks, and variations in use of medications by women with IBD before, during, and after pregnancy. We accessed data on children born to women 15-45 y old from 1990 through 2010, using a mother-child linked dataset from an electronic database of primary care records containing medical diagnoses, events, and drug prescriptions from across the United Kingdom. We identified pregnant women with IBD, and all prescriptions for 5-aminosalicylates azathioprine/6-mercaptopurine, and corticosteroids were extracted from their primary care records. We calculated risks of major congenital anomaly in children of mothers with and without IBD, and in children exposed or not exposed to 5-aminosalicylates, azathioprine/6-mercaptopurine, or corticosteroids during their first trimester of fetal development. Logistic regression with a generalized estimating equation was used to provide risk estimates adjusted for confounders. We calculated proportions of women taking medications before, during, and after pregnancy and assessed whether cessation was associated with subsequent disease flares. Risks of a major congenital anomaly in 1703 children of mothers with IBD and 384,811 children of mothers without IBD were 2.7% and 2.8%, respectively. This corresponded to an adjusted odds ratio of 0.98 (95% confidence interval [CI], 0.73-1.31). In children of women with IBD, the adjusted odds ratios of a major congenital anomaly associated with drug use were 0.82 (95% CI, 0.42-1.61) for 5-aminosalicylates 0.48 (95% CI, 0.15-1.50) for corticosteroids, and 1.27 (95% CI, 0.48-3.39) for azathioprine/6-mercaptopurine. No increases in heart, limb, or genital anomalies were found in children of women with IBD; 31.2% of women discontinued 5-aminosalicylates and 24.6% discontinued azathioprine/6-mercaptopurine in early pregnancy. The risk of flares later in pregnancy was not related to cessation of medication. We found no evidence that IBD during pregnancy or medical therapy for IBD during pregnancy increases the risk of a major congenital anomaly in children. Patients should receive appropriate guidance on use of medication before and during pregnancy.

SAT0539 The Risk of Future Attacks in Patients with Incident Gout: a Population-Based

ObjectivesWhile there appears to be consensus that non-pharmacological uric acid lowering therapies (diet and lifestyle modifications) should be initiated in every patient presenting with gout, there is much less agreement...

THU0490 Canakinumab Treatment of Patients with Hyper-IgD Syndrome: An Open-Label, Multicenter, Pilot Study

BackgroundHyper-IgD and periodic fever syndrome (HIDS) is a recessively inherited autoinflammatory disease caused by melavonate kinase (MVK) gene mutations. It is characterized by recurrent, early-onset, 4-6 days-long acute episodes with...

AB0642 Efficacy of anakinra in gouty arthritis in real life population: a report of 36 cases.

BackgroundGout is a common arthritis that occurs particularly in subjects who have frequently associated comorbidities. These comorbid conditions could limit the use of conventional therapies (e.g. colchicine, non-steroidal anti-inflammatory drugs...

Initiation of Allopurinol at First Medical Contact for Acute Attacks of Gout: A Randomized Clinical Trial

ObjectiveStreamlining the initiation of allopurinol could result in a cost benefit for a common medical problem and obviate the perception that no treatment is required once acute attacks have resolved. Our objective was to test the hypothesis that there is no difference in patient daily pain or subsequent attacks with early versus delayed initiation of allopurinol for an acute gout attack. MethodsA total of 57 men with crystal-proven gout were randomized to allopurinol 300 mg daily or matching placebo for 10 days. All subjects received indomethacin 50 mg 3 times per day for 10 days, a prophylactic dose of colchicine 0.6 mg 2 times per day for 90 days, and open-label allopurinol starting at day 11. Primary outcome measures were pain on visual analogue scale (VAS) for the primary joint on days 1 to 10 and self-reported flares in any joint through day 30. ResultsOn the basis of 51 evaluable subjects (allopurinol in 26, placebo in 25), mean daily VAS pain scores did not differ significantly between study groups at any point between days 1 and 10. Initial VAS pain scores for allopurinol and placebo arms were 6.72 versus 6.28 (P=.37), declining to 0.18 versus 0.27 (P=.54) at day 10, with neither group consistently having more daily pain. Subsequent flares occurred in 2 subjects taking allopurinol and 3 subjects taking placebo (P=.60). Although urate levels decreased rapidly in the allopurinol group (from 7.8 mg/dL at baseline to 5.9 mg/dL at day 3), sedimentation rates and C-reactive protein levels did not differ between groups at any point. ConclusionsAllopurinol initiation during an acute gout attack caused no significant difference in daily pain, recurrent flares, or inflammatory markers.