Flare Rate Research Articles

Outcomes of gout in patients with cirrhosis: A national inpatient sample-based study.

Hyperuricemia is a prerequisite for the development of gout. Elevated serum uric acid (UA) levels result from either overproduction or decreased excretion. A positive correlation between serum UA levels, cirrhosis-related complications and the incidence of nonalcoholic fatty liver disease has been established, but it is unknown whether hyperuricemia results in worsening cirrhosis outcomes. We hypothesize that patients with cirrhosis will have poorer gout outcomes. To explore the link between cirrhosis and the incidence of gout-related complications. This was a cross-sectional study. The national inpatient sample was used to identify patients hospitalized with gout, stratified based on a history of cirrhosis, from 2001 to 2013 via the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality, gout complications and joint interventions. The χ 2 test and independent t-test were performed to assess categorical and continuous data, respectively. Multiple logistic regression was used to control for confounding variables. Patients without cirrhosis were older (70.37 ± 13.53 years vs 66.21 ± 12.325 years; P < 0.05). Most patients were male (74.63% in the cirrhosis group vs 66.83%; adjusted P < 0.05). Patients with cirrhosis had greater rates of mortality (5.49% vs 2.03%; adjusted P < 0.05), gout flare (2.89% vs 2.77%; adjusted P < 0.05) and tophi (0.97% vs 0.75%; adjusted P = 0.677). Patients without cirrhosis had higher rates of arthrocentesis (2.45% vs 2.21%; adjusted P < 0.05) and joint injections (0.72% vs 0.52%; adjusted P < 0.05). Gout complications were more common in cirrhosis. Those without cirrhosis had higher rates of interventions, possibly due to hesitancy with performing these interventions given the higher complication risk in cirrhosis.

Risk of systemic lupus erythematosus flares according to autoantibody positivity at the time of diagnosis

To estimate the risk of systemic lupus erythematosus (SLE) flares based on the autoantibody positivity at the time of SLE diagnosis. This retrospective cohort study included 228 patients with newly diagnosed SLE. Clinical characteristics including autoantibody positivity at the time of diagnosis of SLE were reviewed. Flares were defined as a new British Isles Lupus Assessment Group (BILAG) A score or BILAG B score for at least one organ system. Multivariable Cox regression analyses were performed to estimate the risk of flares according to autoantibody positivity. Anti-dsDNA, anti-Sm, anti-U1RNP, anti-Ro, and anti-La antibodies (Abs) were positive in 50.0%, 30.7%, 42.5%, 54.8%, and 22.4% of the patients, respectively. The incidence rate of flares was 28.2/100 person-years. Multivariable Cox regression analysis, adjusted for potential confounders, revealed that anti-dsDNA Ab positivity (adjusted hazard ratio [HR]: 1.46, p = 0.037) and anti-Sm Ab positivity (adjusted HR: 1.81, p = 0.004) at the time of diagnosis of SLE were associated with higher risk of flares. To better delineate the flare risk, patients were categorized as double-negative, single-positive, double-positive for anti-dsDNA and anti-Sm Abs. Compared with double-negativity, double-positivity (adjusted HR: 3.34, p < 0.001) was associated with higher risk of flares, while anti-dsDNA Ab single-positivity (adjusted HR: 1.11, p = 0.620) or anti-Sm Ab single-positivity (adjusted HR: 1.32, p = 0.270) was not associated with higher risk of flares. Patients who are double-positive for anti-dsDNA and anti-Sm Abs at the time of the diagnosis of SLE are at higher risk of flares and may benefit from stringent monitoring and early preventive treatment.

Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile Spondyloarthritis (BACK-OFF JSpA): study protocol for a randomized pragmatic trial

BackgroundThe effectiveness of biologic therapies, primarily tumor necrosis factor inhibitors (TNFi), for children with spondyloarthritis (SpA) has made inactive disease a realistic patient outcome. However, biologic therapies are costly, primarily delivered by subcutaneous or intravenous route, and have non-trivial side effects. Many patients and families want to know if biologic medications can be discontinued after inactive disease is achieved. It remains unclear whether medication dose should remain unchanged, tapered (increase the time between doses), or discontinued once when inactive disease is attained.MethodsThe Biologic Abatement and Capturing Kids’ Outcomes and Flare Frequency in Juvenile SpA (BACK-OFF JSpA) trial is a multicenter pragmatic trial that will randomize 198 participants ages 8–21 years old with SpA and sustained inactive disease on standard TNFi dosing to (1) continue standard TNFi dosing, (2) fixed longer dosing intervals of TNFi, or (3) stop TNFi. The trial will compare the hazard rate of protocol-defined flare and participants’ emotional health among the 3 groups over 12 months. Innovative aspects of this trial are the involvement of patient and parent stakeholders in the design and conduct of the study as well as an electronic health record-based enhanced recruitment strategy.DiscussionThis is the first randomized pragmatic trial to assess the efficacy of TNFi de-escalation strategies in children with JSpA with sustained inactive disease. This research will improve the evidence base that patients, caregivers, and rheumatologists use to make shared decisions about continued treatment versus de-escalation of TNFi therapy in this population.Trial registrationClinicalTrials.gov NCT04891640. Registered on 18 May 2021.

Hydroxychloroquine Therapy in Sarcoidosis-Associated Uveitis

ABSTRACT Background/purpose To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis Methods Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital. Results Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7–25) to 5.0 (IQR, 3–6.5) mg/day (p = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years (p = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects. Conclusion Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis. Abbreviations: AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d’Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature

Clinical characteristics of psoriatic arthritis and axSpA patients with uveitis

Introduction/ObjectiveTo describe the clinical characteristics and risk factors for uveitis flare in our psoriatic arthritis and axSpA patient cohorts and to describe possible associations of the different disease domains and uveitis flares. Methodology and methodsRetrospective analysis of patients followed prospectively in the SpA and PsA clinics at the Toronto western hospital (January 2004–December 2020). ResultsOf the 3306 included, 1724 patients had axSpA and 1582 PsA. 30.2% of the axSpA cohort, and 7.6% of the PsA population were diagnosed with uveitis. The annual rate of flares per person at risk was 12.1% in the axSpA cohort, vs 1.7 in the PsA. In the axSpA patients, 68% were HLA*B27+, compared 16% of the PsA patients. In the axSpA cohort, higher CRP (HR 1.009, p=.004) increased the risk of a uveitis flare, while biologic agents decreased the risk of flare (HR .702, p=.040) in patients with uveitis. In the PsA cohort, being HLA*B27+ (HR 3.084, p=.007) increased the risk of a uveitis flare, while being on a DMARD decreased the risk of a flare in patients with uveitis (HR .262, p=.0088). ConclusionsUveitis is a common complication seen in inflammatory arthritis, with a prevalence of 30% in the SpA vs 7.6% in PsA. Uveitis is more common in the axSpA population than in PsA. Even though HLA-B27 is more common in the axSpA population, it constitutes a risk for uveitis only in the PsA population.

P750 Biosimilar Infliximab Switching is Not Associated with Adverse Outcomes: A Real-World Effectiveness Analyses in a National U.S. Cohort of U.S. Military Veterans with Inflammatory Bowel Disease

Abstract Background Infliximab (IFX) biosimilars are widely available for Crohn’s disease (CD) and ulcerative colitis (UC). However, implementation of biosimilar switching has been highly variable in the U.S. Barriers to switching include patient and provider concerns of lower efficacy, immunogenicity, and safety. Biosimilar switching in Veterans Affairs (VA) was based on local facility policy rather than patient/provider selection and thus less prone to selection bias. The goal of this study is to evaluate the safety and effectiveness of biosimilar switching in a National U.S. Cohort of Veterans with CD and UC. Methods We conducted a retrospective cohort study of CD and UC patients who received maintenance originator IFX from 2017-2019 in the VA. CD and UC patients were identified using a previously validated algorithm and confirmed by chart review. Patents on maintenance IFX originator were identified by dispensed medication from Corporate Data Warehouse (CDW). Patients switched to IFX biosimilar after 2017 were identified in CDW by dispensed medication and confirmed by chart review. Adverse outcomes were defined as infusion reaction, serious infection (intravenous antibiotic, delay of IFX), immunogenicity (anti-IFX antibody or IFX escalation) or disease flare (escalation of steroid, IBD related Emergency department visit, hospitalization) confirmed by chart review. Adverse event rates at 12 months for patients continued on originator IFX were compared to patients switched to IFX biosimilar using univariate and multivariate logistic regression models adjusting for patient and non-patient factors. Results A total of 790 patients (492 CD, 298 UC) on originator IFX were identified during the study period. Of these, 380 patients were identified to have switched to IFX biosimilar and 410 patients continued on IFX originator during the study period. Overall adverse outcomes occurred in 35.6% of patients at 12 months (35.6% switch, 35.3% non-switch, p=0.87). No statistically significant difference in rates of infusion reaction, serious reaction, immunogenicity, or IBD flare were identified between switch and non-switch groups. In multivariate logistic regression including age, race, gender, concomitant medication, and VA priority status, no significant differences in adverse outcomes at 12 months were observed between switch and non-switch groups (aOR 1.09, 95% CI 0.76-1.42). Conclusion In a real-world national U.S. cohort of patients with CD and UC, we observed IFX biosimilar switching was not associated with adverse events compared to continuation on IFX originator. While this study may be underpowered to detect such a small difference, these findings provide further reassurance that IFX biosimilar switching for CD and UC is safe and effective.

Mycophenolate Mofetil for Systemic Lupus Erythematosus: Our 20-Year Experience.

Mycophenolate mofetil (MMF) has been long used in the treatment of systemic lupus erythematosus (SLE). Further studies are warranted to investigate its long-term use in maintenance treatment of lupus nephritis (LN). The purpose of this study was to describe our practice experience using MMF with regard to its indications, safety, tolerability, and treatment efficacy. We sought to identify rates of renal remission, flare and progression to end-stage renal disease (ESRD). In this retrospective chart review, we identified all patients treated with MMF between 1999 and 2019. Descriptive statistics were used to identify occurrence of remission, occurrence of flares, progression to ESRD, and occurrence of adverse effects. One hundred and one patients were treated with MMF for a mean duration of 69 months. The most common indication was LN (90%). Among patients with LN, 60% achieved complete remission and 16% achieved partial remission at one-year follow-up. Ten patients flared while on maintenance therapy and seven patients flared after treatment was discontinued. Of the 40 patients who were treated for at least five years, one patient developed a flare. Of the 13 patients who were treated for at least 10 years, none developed a flare.One patient on maintenance therapy progressed to ESRD. The most common adverse effects were leukopenia (9%), nausea (7%) and diarrhea (6%). Maintenance treatment with MMF constitutes an effective long-term treatment for lupus nephritis. Our practice demonstrates its tolerability over many years with few adverse effects, prevention of renal flares, and a low progression rate to ESRD.

REAL-WORLD EXPERIENCE WITH TOFACITINIB DOSE DE-ESCALATION IN PATIENTS WITH MODERATE AND SEVERE ULCERATIVE COLITIS

Abstract BACKGROUND Tofacitinib is associated with sustained steroid-free remission and improved quality of life in patients with ulcerative colitis (UC), with the lowest effective dose recommended for maintenance therapy. However, there is limited real-world data to guide decision on optimal maintenance dose. We aimed to evaluate treatment outcomes of tofacitinib dose de-escalation in patients with UC in a real-world cohort. METHODS Included were adults with moderate-severe UC treated with tofacitinib between 1/2012-1/2022. Duration of treatment induction with 10 mg twice daily was 8, 16, or &amp;gt;16 weeks. Dose de-escalation was defined as decrease to 5 mg twice daily. Primary outcome was UC flare, defined as UC-related hospitalization/surgery, reinduction with tofacitinib dose increase, corticosteroid, or change of therapy class. Predictors of UC flare were explored using univariable and multivariable Cox regression. RESULTS Among 162 patients, 54% were male and 71% were white with a median age of 38 years, with 41% and 51% having moderate and severe UC, respectively. Eighty-three (52%) patients continued induction dose while 79 (48%) underwent dose de-escalation. There was no significant difference in number of prior biologic use or baseline endoscopic Mayo score, however, patients who underwent de-escalation were less likely to be steroid dependent during induction (50% vs 70%,p=0.01). After a median follow-up of 12 months, cumulative incidence rates of UC flare at 12 months were similar in patients with and without dose de-escalation (56% vs 58%,p=0.81), though patients without dose de-escalation had higher rates of UC-related hospitalization (27% vs 14%,p=0.04) and change of therapy class (39% vs 12%,p&amp;lt;0.01) compared to those who de-escalated. Among patients with dose de-escalation, cumulative rates of UC flare at 12 months were higher in patients with ongoing severe disease (Mayo 3) at 6 months of tofacitinib (Figure 1). In univariable Cox regression, prolonged duration of induction course with 10 mg twice daily &amp;gt;16 weeks was protective of UC flare (HR 0.37,95% CI 0.16-0.85) while ongoing severe disease (Mayo 3) was associated with UC flare (HR 6.41,95% CI 2.23-18.44), which remained significant after adjusting for age, sex, duration of induction course, and use of corticosteroid at dose de-escalation (HR 6.05, CI 2.00-18.35) (Table 1). Twenty-seven (29%) patients with UC flare had dose re-escalated to 10 mg twice daily with 63% recapturing clinical response at 12 months. CONCLUSIONS In this real-world cohort of UC patients with tofacitinib de-escalation, we observed a 56% cumulative incidence of UC flare at 12 months. Observed factors associated with UC flare after dose de-escalation included shorter induction course &amp;lt;16 weeks and active disease at 6 months of tofacitinib. The majority were able to recapture clinical response after dose re-escalation.

Postoperative flares and peri-arthroscopic management of immunosuppressive medications in patients with rheumatic disease

PurposeTo determine the rate and characteristics of postoperative flares in rheumatic disease patients undergoing arthroscopic surgery, and the role of perioperative immunosuppression (IS) management in preventing or provoking these exacerbations. MethodsWe conducted a retrospective review of arthroscopic surgeries in patients with rheumatologic disease over 11 years. Patients taking IS at baseline and those without were matched 1:1 using propensity scores on age, sex, rheumatic disease type, and procedure complexity. Patients taking IS at baseline were sub-divided into those remaining on IS perioperatively versus those who held IS before surgery. Multivariable logistic regression identified risk factors for postoperative flares for the three IS groups, and survival analysis was used to compare the probability of remaining flare-free up to 12 weeks postoperatively. ResultsAfter matching, 428 patients (214 on various types of baseline IS, 214 not on baseline IS) were included, with 110 on baseline IS remaining on it perioperatively. Rates of postoperative flares were similar for those staying on vs holding their baseline IS (9.1% vs 9.6%) but flares were less frequent in patients not on baseline IS (1.9%). Patients who remained on perioperative IS did not have significantly less flares compared to patients taken off perioperative IS (OR 0.764 [0.267, 2.181]; p = 0.61). Patients not on baseline IS had a significantly higher probability ofremaining flare-free up to 12 weeks (p = 0.004). ConclusionRheumatic disease patients who hold IS medication before undergoing arthroscopy, out of concern for potential infection or complications, do not significantly increase their risk of flaring their autoimmune disease whether they had been taking csDMARDs or biologic agents. Those not taking any IS at baseline have a much lower risk of post-arthroscopic flaring, though as a group they likely harbor less of an autoimmune burden.

Anti-SARS-CoV-2 vaccination in adolescent and adult patients with juvenile-onset systemic lupus erythematosus: tolerability and impact on disease activity.

JSLE has a severe presentation and a remitting course. Patients with JSLE carry an increased vulnerability to infections, which also act as triggers of disease flare. Thus, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important tool in JSLE. The objective of this study is to evaluate the tolerability and the safety of anti-SARS-CoV-2 vaccination, including the booster, in a monocentric cohort of JSLE patients. Clinical records of JSLE patients who received at least one dose of any anti-SARS-CoV-2 vaccine were retrospectively reviewed. Data about disease activity, treatment, anti-SARS-CoV-2 vaccination and COVID-19 infection were collected. Sixty-five JSLE patients received at least one dose of anti-SARS-CoV-2 vaccination, while 46 patients completed the schedule with the booster. The rate of mild-moderate adverse events was 66%, mainly comprising fever, fatigue, arthromyalgias and pain at injection site. The rate of adverse events after the booster was similar to that registered after the first two doses. No significant changes after SARS-CoV-2 vaccination in BILAG and SLEDAI were observed. Disease flare rate (mainly LN) after immunization was 10.8%. Flares occurred predominantly in patients with moderate disease activity before immunization; accordingly, SLEDAI ≥4 identified patients at risk of flare while Lupus Low Disease Activity State (LLDAS) plays a protective role against post-vaccination flare. This study confirms that anti-SARS-CoV-2 vaccination in JSLE is well tolerated; a strict clinical monitoring and a thoughtful choice of vaccination timing should be devoted to patients not in LLDAS due to the risk of post-vaccine flare.

Hydroxychloroquine daily dose, hydroxychloroquine blood levels and the risk of flares in patients with systemic lupus erythematosus

BackgroundRecent guidelines for SLE recommend using a hydroxychloroquine (HCQ) dose less than 5.0 mg/kg/day to reduce the risk of retinopathy. To determine if this dose reduction would have an impact...

Low Profile GRIN Lenses With Integrated Matching Using 3-D Printed Ceramic

In this paper, we investigate a shortened horn antenna with high gain that is enabled by a 3D-printed gradient index (GRIN) lens composed of high permittivity zirconia <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$(ZrO_{2})$ </tex-math></inline-formula> . The baseline H-plane sectoral horn antenna is designed with length that is 1/3 of the optimal horn antenna and exhibits a low gain due to the high flaring rate of the horn. Increased gain is achieved by adding a flat GRIN lens at the horn aperture. High permittivity <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ZrO_{2}\,\,(\varepsilon _{r} = 23)$ </tex-math></inline-formula> enables lens miniaturization; however, when interfaced with air, reflections at the air interface increase the impedance mismatch. Two different methods for mitigating the reflections are studied. One is a simple <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\lambda /4$ </tex-math></inline-formula> matching layer that matches the bulk permittivity of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ZrO_{2}$ </tex-math></inline-formula> to air. As expected, the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\lambda /4$ </tex-math></inline-formula> layers reduce the reflections in part of the 13–18 GHz band but produce high reflection in other parts. The second approach is a GRIN lens with integrated tapered matching layer to match phase and impedance simultaneously. Three tapering methods are studied (exponential, Klopfenstein, linear) for impedance matching. Analytical expressions of the minimum thickness and permittivity distribution are derived. The lens is discretized for print and three types of unit cells are proposed to create a wide range of permittivities ranging from bulk ceramic to air. A <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$ZrO_{2}$ </tex-math></inline-formula> lens prototype printed with an XJet Carmel 1400 is measured and results show good agreement with simulations, including gain performance equivalent to a horn of 2.4x longer length. The measured gain and beamwidth of the lens are 5.4dB higher and 52° narrower than those of the shortened horn alone at 15 GHz, respectively.

The Effect of Leflunomide as Adjunctive Therapy With a TNF Inhibitor in Pediatric Patients With Uveitis.

To describe the effectiveness of leflunomide as adjunctive therapy with anti-tumor necrosis factor (anti-TNF) agents in pediatric patients with uveitis who are not able to tolerate methotrexate. A retrospective case series was performed of pediatric patients who were receiving leflunomide in conjunction with anti-TNF agent therapy after intolerance to a combination of methotrexate with anti-TNF therapy. Dose and duration of methotrexate, leflunomide, and anti-TNF therapy were recorded. Extensive history, demographics, laboratory data, and uveitis flare rate were obtained. A total of five children were included in the study. Most patients were initially receiving methotrexate and an anti-TNF agent was added subsequently due to inadequate response to monotherapy. After discontinuation of methotrexate, leflunomide was initiated with anti-TNF therapy. The replacement of methotrexate with leflunomide showed decreased side effects and was associated with lower flare rates and steroid-free remission. Leflunomide was found to be well tolerated and effective at maintaining uveitis quiescence in conjunction with anti-TNF agents in pediatric patients who do not tolerate methotrexate. [J Pediatr Ophthalmol Strabismus. 2023;60(6):417-420.].

Navigating Coronavirus Disease 2019 Vaccination and Uveitis: Identifying the Rates and Risk of Recurrent Uveitis after Coronavirus Disease Vaccination

To identify rates of uveitis reactivation both before and after the coronavirus disease (COVID) 2019 vaccine in subjects with a previous diagnosis of uveitis. Retrospective study. Subjects were identified from the Inflammatory Eye Disease Registry at Auckland District Health Board diagnosed with uveitis between January 1, 2010, and December 31,2020. Date of COVID vaccination was determined from the patient clinical record. Rate of flare was calculated for 3 months before vaccination and 3 months after each vaccination. Uveitis flare was defined as the presence of new uveitis activity or increased activity that required a change in uveitis treatment. A total of 4184 eyes of 3008 patients were included in the study with a total of 8474 vaccinations given during the study period. Median age was 54.8 years, and 1474 (49.0%) were female. Noninfectious etiology was most common, occurring in 2296 patients (76.3%) and infectious etiology occurring in 712 patients (23.7%). Rate of uveitis flare was 12.3 per 1000 patient-months at baseline, 20.7 after the first dose, 15.0 after the second dose, 12.8 after the third dose, and 23.9 after the fourth dose. The median period of quiescence before flare was 3.9 years. An increase in uveitis flare was seen in both infectious uveitis (baseline 13.1 compared with 20.2 after first dose, 154% increase) and noninfectious uveitis (baseline 12.4 compared with 20.9 after first dose, 169% increase). Risk factors for uveitis flare were identified to be recurrent uveitis, chronic uveitis, shorter period of quiescence, and first dose of vaccine. Median time to uveitis flare was 0.53 months after the first vaccination, 1.74 months after the second vaccination, and 1.35 months after the third vaccination. The current study demonstrates an increased risk of uveitis flare after the first dose of COVID vaccination. This risk was highest in those with previous recurrences, chronic uveitis, and shorter period of quiescence. Proprietary or commercial disclosure may be found after the references.

Long-term Experience with Anti-tumor Necrosis factor - α Therapy in the Treatment of Refractory, Non-infectious Intermediate, Posterior, and Panuveitis

ABSTRACT Purpose To study the efficacy and long-term effects of infliximab and adalimumab in patients with active refractory non-infectious intermediate, posterior, or panuveitis (NIPPU). Methods Retrospective, longitudinal study. Results Included were 61 patients (104 eyes) of whom 34 were males (55.74%). Mean age at diagnosis of uveitis was 26.5 ± 16.14 years. All patients had active uveitis at baseline (time of initiation of biological therapy). Median interval between the start of conventional immunomodulatory therapy (IMT) to the introduction of biological therapy was 13.0 (IQR 26.0) months. Ocular inflammation was effectively controlled in 92 eyes (88.46%). The most commonly used TNF-α inhibitor was adalimumab in 47 patients (77%). Mean follow-up time after baseline was 40 ± 34.08 months. In the year preceding the institution of TNF-α inhibitors, the average number of flares was 1.5 ± 1.1/year and it decreased to 0.08 ± 0.29/year in the first year after baseline (p < .0005). Forty-four eyes (42.30%) experienced flare over the entire follow-up period. Mean time to first flare was 14.5 ± 9.26 months. At baseline, the mean dose of prednisone was 25.5-±20.8 mg/day. A marked decrease to a mean prednisone dose of 7.85 ± 9.7 mg/day was observed at 6 months (p = .03). In patients treated with adalimumab, the mean time to prednisone dose ≤7.5 mg/day was 4.02 ± 4.89 months compared to 15.64 ± 21.34 months in patients treated with infliximab (p = .03). 64.3% of patients treated by infliximab had Behçet uveitis compared to 27.7% of patients treated by adalimumab. Eyes treated with adalimumab experienced first flare at a mean time of 14.11 ± 6.29 months, whereas eyes treated with infliximab experienced first flare at 18.29 ± 14.24 months after baseline (p < .0005). The risk for moderate and severe visual loss was lower with shorter duration of uveitis before initiating anti-TNF-α treatment (odds ratio, 0.003; 95% CI, 0.000–0.005; p = .023), better presenting logMAR VA (odds ratio, 0.266; 95% CI, 0.172–0.361; p < .0005) and when adalimumab was used (odds ratio, 0.354; 95% CI, 0.190–0.519, p < .0005). Conclusions Anti-TNF-α therapy was successful in controlling refractory NIPPU in the majority of cases. It significantly reduced flare rate, exerted steroid-sparing effects, and preserved visual potential. Adalimumab use, better initial visual acuity, and earlier introduction of anti-TNF- α therapy were associated with a lower risk of visual loss.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING)

BackgroundStudies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. MethodsA national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. Findings4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53–65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5–0.8) and 0.7 (0.6–0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2–2.0) and 1.4 (1.2–1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1–2), 1.2 (1.1–1.4) and 1.5 (1.2–1.8) for prednisolone ≤7.5 mg respectively]. InterpretationThere was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Reduced Rate of Disease Flares in Japanese Patients with Systemic Lupus Erythematosus: An Altered Balance between the Use of Glucocorticoids and Immunosuppressants in Recent Decades.

Objective This study examined whether or not the disease control in Japanese patients with systemic lupus erythematosus (SLE) had improved in recent years and its possible association with altered balance between the use of glucocorticoids and immunosuppressants. Methods We enrolled Japanese patients with SLE who visited our medical center during 2013-2017 (Group A, 75 patients) and compared them with patients encountered during 1999-2003 (Group B, 69 patients; not overlapping with Group A). Patient background characteristics, doses of glucocorticoids, and the use of immunosuppressants at the times of SLE onset and disease flares were reviewed from the medical records. Disease flare was defined as new British Isles Lupus Assessment Group 2004 A or B scores in at least one system. Results Lupus nephritis and neuropsychiatric manifestations were less frequently observed in Group A than in Group B (p=0.042 and p=0.045, respectively). Although the initial glucocorticoid dosage was similar between the groups, the inclusion rate of immunosuppressants in the initial SLE treatment was significantly higher in Group A than in Group B (56% vs. 6% in Group B, p<0.001). The median number of SLE flares per person-year was significantly lower in Group A than in Group B (0 vs. 0.3, respectively, p<0.001), and a propensity score-matched analysis indicated the association of SLE flare with the non-use of immunosuppressants in the initial treatment (p=0.012). The rates of infectious diseases and other complications were similar between the groups. Conclusion The recent aggressive use of immunosuppressants in Japan resulted in a reduction in the rate of SLE flare.

Stereotactic Body Radiation Therapy vs. Conventional External Beam Radiation Therapy for Painful Bone Metastases: A Systematic Review and Meta-Analysis of Randomized Trials

<h3>Purpose/Objective(s)</h3> The magnitude of benefit and toxicity of stereotactic body radiation therapy (SBRT) compared with conventional external beam radiation therapy (cEBRT) in treating symptomatic bone metastases is unclear due to the conflicting results from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to compare the efficacy and safety of SBRT and cEBRT in patients with previously unirradiated painful bone metastases. <h3>Materials/Methods</h3> We searched various databases and major oncologic conference proceedings from inception to Oct 2021 for RCTs comparing SBRT with cEBRT for previously unirradiated painful bone metastases. The outcomes of interest were efficacy (overall and complete pain response rates, local progression, overall survival (OS) and quality of life (QoL)) and safety (post-irradiation fractures, pain flares and radiation myelopathy). We assessed the methodologic quality of individual trials using the revised Cochrane risk-of-bias (RoB2) tool. We performed one-stage individual patient data meta-analysis using multilevel logistic regression model. Sensitivity analyses were conducted using two-stage frequentist and Bayesian meta-analyses. We adopted Synthesis Without Meta-analysis (SWiM) approach to summarize adverse events and quality of life outcomes. We assessed the certainty of the evidence for the efficacy outcomes using GRADE approach. <h3>Results</h3> Six RCTs including 894 patients were identified. Five of the included trials had low risk of bias. There was no significant difference in overall pain response rates at 3 months between SBRT and cEBRT (odd ratio (OR), 1.10; 95% confidence interval (CI), 0.84-1.44; P, 0.48; GRADE, moderate certainty). SBRT significantly improved complete pain response rates at 3 months (OR, 3.38; 95% CI, 1.88-6.07; P< 0.01; GRADE, high certainty) and reduced local progression rates (OR, 0.15; 95% CI, 0.04-0.53; P< 0.01; GRADE, high certainty), compared to cEBRT. Sensitivity analyses showed consistent findings. SBRT was associated with a modest increase in pain flare rates, compared to cEBRT. There were no significant differences between the two groups in OS, post-irradiation fracture and radiation myelopathy. The QoL was similar, except for improved perception of financial burden with SBRT at 4 weeks. <h3>Conclusion</h3> Among the patients with previously unirradiated symptomatic bone metastases, SBRT significantly improved complete but not overall pain response rates at 3 months and delayed local progression without adversely impacting on the quality of life and overall survival, compared to cEBRT. SBRT was associated with a modest increase in the pain flare rates, compared to cEBRT.

Extending optical flare models to the UV: results from comparing of TESS and GALEX flare observations for M Dwarfs

ABSTRACT The ultraviolet (UV) emission of stellar flares may have a pivotal role in the habitability of rocky exoplanets around low-mass stars. Previous studies have used white-light observations to calibrate empirical models which describe the optical and UV flare emission. However, the accuracy of the UV predictions of models has previously not been tested. We combined TESS optical and GALEX UV observations to test the UV predictions of empirical flare models calibrated using optical flare rates of M stars. We find that the canonical 9000-K black-body model used by flare studies underestimates the GALEX near-ultraviolet (NUV) energies of field age M stars by up to a factor of 6.5 ± 0.7 and the GALEX far-ultraviolet energies of fully convective field age M stars by 30.6 ± 10.0. We calculated energy correction factors that can be used to bring the UV predictions of flare models closer in line with observations. We calculated pseudo-continuum flare temperatures that describe both the white-light and GALEX NUV emission. We measured a temperature of 10 700 K for flares from fully convective M stars after accounting for the contribution from UV line emission. We also applied our correction factors to the results of previous studies of the role of flares in abiogenesis. Our results show that M stars do not need to be as active as previously thought in order to provide the NUV flux required for prebiotic chemistry, however, we note that flares will also provide more FUV flux than previously modelled.

Far-ultraviolet Flares on Accreting Protostars: Weak and Classical T Tauri Stellar Pair Analysis

The far-ultraviolet (FUV) emission of classical T Tauri stars (CTTSs) is known to play an important role in protoplanetary disk dispersal and giant planet formation, yet the role played by protostellar flares in these processes is largely unknown. We use nearby star-forming regions as laboratories to probe the FUV flare characteristics of CTTSs and test whether flares may be masked underneath accretion luminosity. Using AD Leo as our archetypal flare template, we pilot a novel analysis technique on three weak-lined T Tauri star (WTTS) and CTTS pairs: TWA-7/TWA Hya, RECX-1/RECX-11, and LkCa19/GM Aur. We find that flares contribute an upper limit of 0.064% ± 0.002%, 3.1% ± 0.1%, and 2.7% ± 0.3% to the total FUV energy budgets of TW Hya, RECX-11, and GM Aur, respectively. We also present predicted CTTS flare rates, which suggest that we would expect to observe roughly one 5σ flare on each of the CTTS archival light curves. We find one 5σ flare on TW Hya with E(1380–1745 Å) = (6.1 ± 0.7) × 1031 erg, but none are found on RECX-11 or GM Aur. Longer monitoring campaigns are required to provide more concrete constraints on the FUV flare frequency of accreting protostars. Optical TESS data of the targets were also analyzed to contextualize these results. Lastly, we report the first FUV flare on a WTTS (RECX-1), which is also the most energetic FUV flare event observed with the Hubble Space Telescope to date with E(1135–1429 Å) = (2.1 ± 0.1) × 1032 erg.