Flare Group Research Articles

P.016: A comparative analysis of kidney transplantation outcomes in systemic lupus erythematosus patients with disease flare vs. non-flare groups.

P.016: A comparative analysis of kidney transplantation outcomes in systemic lupus erythematosus patients with disease flare vs. non-flare groups.

Beware of misdiagnosis and incorrect treatment of acute gout flare and postoperative infections after arthroscopic surgery for knee gouty arthritis

To analyze the differences of clinical features of acute gout flare and postoperative infection under arthroscopy of knee gouty arthritis patients to offer guiding opinions of clinical diagnosis and treatment. Between January 2017 and December 2022, 235 patients with gouty knee osteoarthritis were admitted, and underwent arthroscopic debridement combined with synovectomy. Among them, 35 cases had fever with a temperature higher than 38 °C postoperatively while acute inflammatory appears under redness, swelling, heat and pain of the operated joints. There were 29 males and 6 females, with an average age of (41.48±13.90) years old. Among them 23 patients were diagnosed with acute gout attack, and recovered well after being given colchicine and prednisolone;12 patients were diagnosed with postoperative joint infection, and were cured after being given anti-infective treatments and cleaning and rinsing of the joint cavity. The two groups of patients were compared and analyzed in terms of preoperative general data, surgical conditions, hematology, joint fluid, limb function and other clinical characteristics. There were no significant difference in the preoperative general data between two groups. The onset of fever in the postoperative acute gout flare group occurred mostly within 48 hours, significantly earlier than that in the postoperative infection group(P=0.037). The visual analogue scale score was significantly higher in the acute gout flare group (5.32±1.38) score than in the postoperative infection group (2.45±0.68) score (P=0.000), while 14 patients with acute gout flare were accompanied by severe pain in other joints. Hematologically, indicators such as white blood cell counts and ratios were significantly higher in both groups. In terms of inflammatory indicators, IL-6, erythrocyte sedimentation rate, procalcitonin and other inflammatory indicators were significantly elevated in both groups, but there was no statistical difference between two groups. The C-reactive protein level in the postoperative infection group (220.97±116.30) mg·L-1 was higher than that in the postoperative acute gout attack group(120.67±82.45) mg·L-1(P=0.006). Blood uric acid (316.55±112.84) μmol·L-1 was higher in the acute postoperative gout flare group than in the postoperative infection group (159.14±126.92) μmol·L-1(P=0.001). In the joint fluid examination of the postoperative infection group, the glucose metabolism indicator was significantly lower than that of the acute gout flare group, and five of them had positive bacterial cultures. The symptoms of acute gout flare could be mistaken as postoperative infection due to their similarity, therefore requires careful differentiation. Differential diagnosis should be based on a combination of clinical signs, hematology and joint fluid findings, and targeted treatment should be given to avoid serious complications.

Psychological impact of life events in systemic lupus erythematosus patients - Differences between flares and remission.

Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients' electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors.

Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan–Meier’s curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan–Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

New Onset and Exacerbation of Autoimmune Bullous Dermatosis Following COVID-19 Vaccination: A Systematic Review.

Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination. We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine. We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation. Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.

COVID-19 Vaccination and Gout Flare Risk in Patients With Infrequent or Frequent Flares: A Prospective Cohort Study.

To assess post-COVID-19 vaccination gout flare risk with differing baseline flare burden. We prospectively studied gout patients with infrequent or frequent flares, defined as ≤1 flare/year or ≥2 flares/year, respectively. COVID-19 vaccine-naive patients managed with urate-lowering therapy between February and June 2021 were included and voluntarily decided on vaccination. Participants were followed for 12 weeks after enrollment or first vaccine dose. Gout flares and risk factors were compared between groups. Of 530 participants, 308 (58.1%) had infrequent flares and 222 (41.9%) had frequent flares at baseline, with 248 (142 infrequent and 106 frequent) receiving two-dose COVID-19 vaccination. Vaccination increased cumulative flare incidence at 12 weeks in the infrequent but not the frequent flare group (26.1% vs 10.8%, P = 0.001, compared with 60.4% vs 65.5%, P = 0.428). Flare incidence in the final 4 weeks of observation decreased significantly only in the vaccinated infrequent flare group (4.3% vs 12.0%, P = 0.017). Multivariable analyses showed that vaccination (odds ratio [OR] 2.82, 95% confidence interval [95% CI] 1.50-5.30, P = 0.001), flare in the preceding year (OR 1.95, 95% CI 1.03-3.71, P = 0.04), and body mass index (OR 1.09, 95% CI 1.01-1.19, P = 0.03) were independently associated with increased flare risk in the infrequent flare group. Baseline serum urate (mg/dl) was an independent risk factor in the frequent flare group (OR 1.23, 95% CI 1.05-1.45, P = 0.012). COVID-19 vaccination was associated with increased early gout flares only in patients with previously infrequent flares.

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry.

To determine the safety and efficacy of anifrolumab in patients with systemic lupus erythematosus (SLE) classified based on the Lupus Low Disease Activity State (LLDAS) in real-world clinical practice. This retrospective observational study involved SLE patients who started anifrolumab therapy. The primary end point was the retention rate over 26 weeks after initiating anifrolumab therapy; 45 patients followed up for 12 weeks or longer were analysed in the following groups to determine the safety and efficacy up to week 12 after treatment initiation: (i) non-LLDAS achievement group and (ii) minor flare group. Safety and efficacy were compared between the minor flare group and the standard of care (SoC) group (treated by adding glucocorticoids [GCs] or immunosuppressants) after adjustment with inverse probability of treatment weighting using propensity score (PS-IPTW). The retention rate of anifrolumab was 89.7% at week 26.The LLDAS achievement rates at week 12 were 42.9% and 66.7% in the non-LLDAS achievement and minor flare groups, respectively. In both groups, GC doses and SELENA-SLEDAI score significantly decreased. When the anifrolumab group with minor flare was compared with the SoC group or the GC dose increase group, the GC dose and SLEDAI score were significantly lower in the anifrolumab group than in either of the other groups; there was no significant difference in LLDAS achievement. At week 26 after initiating anifrolumab therapy, ∼90% of patients remained on therapy. Anifrolumab might lower disease activity without initiating GCs and reduce GC doses, especially in patients who experience minor flares after LLDAS achievement.

STATISTICS OF THERMAL PLASMA PARAMETERS AND NON-THERMAL X-RAY SPECTRA OF SOLAR FLARES WITH HELIOSEISMIC RESPONSE

We present the results of statistical analysis of various thermal plasma parameters and non-thermal X-ray spectra of helioseismically active (producing “sunquakes”) solar flares of the 24th solar cycle up to February 2014. Two samples of flares are compared: with helioseismic activity in the form of sunquakes and a sample of flares without photospheric disturbances. The dependences of the considered flare parameters on the energy of helioseismic disturbances are also investigated. Quantitative parameters of solar flares are taken from the statistical work of the Global Energetics series by Markus Ashwanden in 2014–2019. We consider thermodynamic plasma parameters derived from the analysis of RHESSI X-ray spectra and differential emission measure (from AIA EUV images), as well as the characterization of non-thermal X-ray spectra from RHE-SSI. Statistical analysis confirmed that helioseismically active solar flares are characterized by significantly larger fluxes of non-thermal X-ray emission compared to flares without photospheric perturbations. A good linear relationship between helioseismic energy and the total flux of non-thermal X-ray radiation and the total energy of accelerated electrons is found. It is shown that the power-law index of the nonthermal X‑ray spectrum is not the parameter by which one can separate the two groups of flares under consideration. The analysis of the X-ray thermal spectra shows a slight difference between the flares with the sunsets.

Urine and Plasma Complement Ba Levels During Disease Flares in Patients With Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Although the alternative complement pathway has been implicated in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the specific nature of its involvement is unclear. This study measured levels of urine and plasma complement fragment Ba at multiple time points in a group of patients with AAV. The complement fragment Ba was measured by enzyme-linked immunosorbent assay in serial urine and plasma samples from 21 patients with AAV who developed a renal flare, 19 who developed a nonrenal flare, and 20 in long-term remission. Urine Ba levels were corrected for urine creatinine concentration. Changes in Ba levels were modeled using mixed linear-effect models. A logistic regression model was fit to predict a renal flare using Ba levels at the time of flare versus the nonrenal flare and long-term remission groups. Data from 60 patients with AAV were used for this analysis; 53% were male, 93% were White, and 74% had antiproteinase3-ANCA. Urine Ba levels increased at renal flare (P< 0.001) but remained stable during a nonrenal flare or long-term remission. Plasma Ba levels were stable over time in all groups. Urine Ba levels predicted a renal flare with an area under the curve of 0.76 (P< 0.001), with a cutoff of 12.53 ng/mg urine creatinine yielding a sensitivity of 76.2% and a specificity of 68.4%. Urine Ba levels, but not plasma Ba levels, are increased at the time of a renal flare in AAV, suggesting intrarenal complement activation and highlighting the potential use of this biomarker for surveillance of active renal vasculitis.

Severe lupus flare is associated with a much higher risk of stroke among patients with SLE.

There are few data on the influence of lupus flare on stroke risk in systemic lupus erythematosus (SLE). In this study, we examined whether a severe lupus flare further increases the risk of stroke among SLE patients. Using the Taiwan's National Health Insurance Research Database, we conducted a retrospective population-based cohort study from 2000 to 2016. Each patient with SLE was matched to a non-SLE subject in age, sex, and index date. A severe flare of lupus was identified when an SLE patient was admitted for pulse therapy with intravenous methylprednisolone greater than 250 mg in a single hospitalization. SLE patients were divided into severe flare and non-severe flare groups. In total, 334 of 10,006 patients with SLE had a severe lupus flare, and the remaining 9672 patients were assigned to the non-severe flare group. Ischemic stroke occurred in 29 (8.7%), 485 (5%), and 384 (3.8%) of the patients in the severe flare, non-severe flare, and control groups, respectively. Hemorrhagic stroke occurred in 9 (2.7%), 123 (1.3%), and 37 (0.4%) of patients in the severe flare, non-severe flare, and control groups, respectively. Compared with patients in the non-severe flare group, patients with severe flare had a significantly higher risk of ischemic stroke (adjusted hazard ratio (aHR) = 7.44, 95% confidence interval (CI): 4.93-11.25 vs aHR = 1.52, 95% CI: 1.26-1.83) and hemorrhagic stroke (aHR = 22.49, 95% CI: 10.09-50.12 vs aHR = 4.47, 95% CI: 2.90-6.90). Severe lupus flare is associated with a much higher risk of ischemic and hemorrhagic strokes among SLE patients.

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

The influence of repeated flares in response to therapy and prognosis in lupus nephritis.

Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

Longitudinal trends of systemic lupus erythematous hospitalizations in the United States: a two-decade population-based study.

Longitudinal data are limited on systemic lupus erythematosus (SLE) hospitalizations. We aim to study longitudinal trends of SLE hospitalizations in the last 2 decades in the United States (U.S). Data were obtained from the National Inpatient Sample database (NIS). We performed a 21-year longitudinal trend analysis of NIS 1998-2018. We searched for hospitalizations for adult patients with a "principal" diagnosis of SLE (SLE flare group) and those with "any" diagnosis of SLE (all SLE hospitalization group) using ICD codes. All non-SLE hospitalizations for adult patients were used as the control. Multivariable logistic and linear regression were used appropriately to calculate adjusted p-trend for the outcomes of interest. Incidence of SLE flare hospitalization reduced from 4.1 to 3.2 per 100,000 U.S persons from 1998 to 2018 (adjusted p-trend < 0.0001). The proportion of all hospitalized patients with SLE admitted principally for SLE reduced from 11.3% in 1998 to 5.7% in 2018 (adjusted p-tend < 0.0001). The proportion of hospitalized blacks in the SLE flare and all SLE hospitalization groups increased from 37.7% and 26.9% in 1998 to 44.7% and 30.7% in 2018 respectively (adjusted p-trend < 0.0001). The proportion of hospitalized Hispanics and Asians disproportionally increased in SLE flare hospitalizations compared to the control group. The incidence of hospitalization for SLE flare has reduced in the last 2 decades in the U.S. The proportion of hospitalized patients with SLE admitted principally for SLE has reduced significantly over time. However, the burden of SLE hospitalizations among ethnic minorities has increased over time. Key Points • The incidence of hospitalization for SLE flare has reduced in the last 2 decades in the U.S. • The proportion of hospitalized patients with SLE admitted principally for SLE has reduced significantly over time. • The burden of SLE hospitalizations among ethnic minorities such as blacks has increased over time.

P1.12-04 The FLARE score and circulating neutrophils are associated with poor Covid-19 outcomes in patients with thoracic cancers

P1.12-04 The FLARE score and circulating neutrophils are associated with poor Covid-19 outcomes in patients with thoracic cancers

Predictors of flare in rheumatoid arthritis patients with persistent clinical remission/low disease activity: Data from the TARAC cohort.

To identify predictors of rheumatoid arthritis (RA) disease activity flare in RA patients who achieved low disease activity (LDA) or persistent remission from the observational Thai Army Rheumatoid Arthritis Cohort study.RA patients with persistent clinical remission, defined by disease activity score 28 (DAS28) < 2.6 and LDA defined by DAS28 ≤ 3.2 for 3 consecutive months, were recruited and followed-up for at least 2 years. The flare was defined by an escalation of DAS28 ≥ 1.2 plus their physicians’ decision to enhance RA treatment. Differences between sustained remission/LDA and flare groups were analyzed, by Chi-square test and unpaired Student t test. Multivariate Cox proportional hazard regression analysis was conducted to determine flare predictors.From 199 RA patients, female were 82.9%. Anticitrullinated peptide antibodies (ACPA) or Rheumatoid factor (RF) were found in 69.8% of patients. Flares occurred in 69 patients (34.9%). Multivariate analysis found that the timescale from symptoms emergence to DMARD commencement, the timescale from DMARD commencement to when RA patients showed remission/LDA, the occurrence of RF or ACPA, LDA (in contrast to remission) and the increased DAS28 score when remission/LDA was achieved and tapering DMARDs promptly when persistent remission/LDA was achieved were predictors of RA flares with hazard ratios of (95% confidence interval [CI]) of 1.017 (1.003–1.030), 1.037 (1.015–1.059), 1.949 (1.035–3.676), 1.926 (0.811–4.566), 2.589 (1.355–4.947), and 2.497 (1.458–4.276), respectively.These data demonstrated that early and aggressive DMARDs treatment approach could maintain remission espcially in seropositive patients. Tapering should be applied minimally 6 months after reaching remission.

The FLARE score, circulating neutrophils, and association with COVID-19 outcomes in patients with solid tumors.

2551 Background: Inflammation and neutrophils play a central role in severe Covid-19 disease. In previous data, we showed that the FLARE score, combining both tumor and Covid-19-induced proinflammatory status (proinflam-status), predicts early mortality in cancer patients (pts) with Covid-19 infection. We aimed to assess the impact of this score in a larger cohort and characterize the immunophenotype (IF) of circulating neutrophils. Methods: Multicenter retrospective cohort (RC) of pts with cancer and Covid-19 infection across 14 international centers. Circulating inflammatory markers were collected at two timepoints: baseline (-15 to -45d before Covid-19 diagnosis) and Covid-19 diagnosis. Tumor-induced proinflam-status was defined by high dNLR (neutrophils/(leucocytes-neutrophils)&gt;3) at baseline. Covid-19-induced proinflam-status was defined by +100% increase of dNLR between both timepoints. We built the FLARE score combining both Tumor and Infection-induced inflammation: T+/I+ (poor), if both proinflam-status; T+/I- (T-only), if inflammation only due to tumor; T-/I+ (I-only), if inflammation only due to Covid; T-/I- (favorable), if no proinflam-status. The IF of circulating neutrophils by flow cytometry was determined in a unicenter prospective cohort (PC) of pts with cancer during Covid-19 infection and in healthy volunteers (HV). Primary endpoint was 30-day mortality. Results: 524 pts were enrolled in the RC with a median follow-up of 84d (95%CI 78-90). Median age was 69 (range 35-98), 52% were male and 78% had baseline PS &lt;1.Thoracic cancers were the most common (26%). 70% had active disease, 51% advanced stage and 57% were under systemic therapy. dNLR was high in 25% at baseline vs 55% at Covid-19 diagnosis. The median dNLR increase between both timepoints was +70% (IQR: 0-349%); 42% had +100% increase of dNLR. Pts distribution and mortality across FLARE groups is resumed in the Table. Overall mortality rate was 26%. In multivariate analysis, including gender, stage and PS, the FLARE poor group was independently associated with 30-day mortality [OR 5.27; 1.37-20.3]. 44 pts were enrolled in the PC. Median circulating neutrophils were higher in pts with cancer (n=10, 56.7% [IQR: 39-78.4%]) vs HV (n=6, 35.8% [IQR: 25.6-21%]), and particularly higher in pts with cancer and severe Covid-19 infection (n=7, 88.6% [IQR: 80.9-94%] (p=0.003). A more comprehensive characterization of the IF of circulating neutrophils, including Lox1/CD62/CD64, will be presented at ASCO. Conclusions: The FLARE score, combining tumor and Covid-19-induced proinflam-status, can identify the population at higher risk for mortality. A better characterization of circulating neutrophils may help improve the prediction of Covid-19 outcomes in pts with cancer. [Table: see text]

Clinical and histological findings at second but not at first kidney biopsy predict end-stage kidney disease in a large multicentric cohort of patients with active lupus nephritis

ObjectiveTo investigate second kidney biopsy as predictor of end-stage kidney disease (ESKD) in active lupus nephritis (LN).MethodsPatients with biopsy-proven LN (International Society of Nephrology/Renal Pathology Society 2003) who had undergone...

Flexible Antagonist versus Agonist Flare Protocol in Women above 40 Undergoing IVF, A retrospective Cohort Study.

Several strategies have been proposed for ovarian stimulation in older women, such as using an increased daily dose of gonadotropins (300-450 IU per day) with GnRH agonist (long or micro dose flare protocols), or using GnRH antagonist protocols. The objective of this study is to compare the efficacy of flexible GnRH antagonist protocol and GnRH agonist flare - pituitary block protocols for ovarian stimulation in women above 40 years old undergoing IVF. This study was performed between January 2016 and February 2019. One hundred and fourteen women aged between 40 and 42 years who underwent IVF were divided into two groups; group I were treated by Flexible GnRH antagonist protocol (Antagonist group, n=68); and group II were treated by Flare GnRH agonist protocol (Flare group, n=46). Patients treated with the antagonist protocol had a significantly lower cancellation rate when compared with patients treated with flare agonist protocol (10.3% vs. 21.7%, p value 0.049). The other parameters evaluated did not show statistically significant differences. Our finding showed that both Flexible antagonist and Flare agonist protocols had comparable outcomes, with lower cycle cancellation rates for older patients treated with the antagonist protocol.

Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis.

Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN). Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry. There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0ng/mL); p=0.012]. ROC curve analysis demonstrated that HCQ levels≤1075ng/mL were associated with a 5.08 (95%CI 1.28-20.13; p=0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, p=0.013). We demonstrated that HCQ blood cut-off level under 1075ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.

What Is a Flare? The Manitoba Living With IBD Study.

Flare is a poorly defined term used by patients and clinicians to indicate inflammatory bowel disease (IBD) status. This study aimed to evaluate the validity of a single-item 7-point flare indicator relative to other measures of disease flare. The longitudinal Manitoba Living with IBD Study followed persons with IBD for 1 year; they completed biweekly online surveys and provided 3 stool samples. Disease flare on a single-item flare indicator with 7 possible responses developed for the study was defined by report of symptoms as "moderately" or "much" worse. The flare indicator was evaluated against 5 measures of disease activity: fecal calprotectin score (FCAL), a 2-point disease status indicator, a 4-point flare certainty indicator, the IBD Symptom Index short form (SIBDSI), and the short form IBD Questionnaire (SIBDQ). Participants in a flare, based on the 7-point measure, were matched to a nonflaring participant, and a stool sample was collected. Of the 155 IBD participants, almost half (n = 74) experienced a flare. Of those who flared, 97.0% endorsed active IBD on the 2-point indicator (controls 42.5%; P < .001); 91.9% endorsed active IBD on the 4-point certainty indicator (controls 32.9%; P < .001); 90.5% endorsed active disease on the SIBDSI (controls 34.2%; P < .001); and 48.5% had an elevated FCAL (controls 34.3%; P < .05). The mean SIBDQ was lower for the flare group compared with controls (43.9 [SD 11.1] vs 58.3 [SD 8.5]; P < .001), indicating worse disease. The 7-point flare indicator robustly identified symptomatic flares. This patient self-report indicator reflected meaningful changes in more complex clinical indices and had only weak concordance with the presence of inflammation.