Risk Of Flare Research Articles

1295-P: The Association between Risk of Gout Flares and Monosodium-Urate Burden Assessed Using Musculoskeletal Ultrasound in Patients with Gout

Objective: We aimed to investigate the association between the risk of gout flares and ultrasound (US)-detected monosodium urate (MSU) burden using two different US score. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal ultrasound examinations of their knees, ankles, and feet. The Outcome Measure in Rheumatology (OMERACT) and musculoskeletal ultrasound features-based (MSUS) score were used to quantify the MSU burden of gout. Odds ratios for the risk of frequent gout attacks were calculated. Results: We enrolled 1253 patients with gout (median age, 46 years; gout duration, 5 years; males, 95.9%) and a median of 3 flares over the past year. Of these, 275 (21.9%) patients had frequent (≥7) gout attacks. The OMERACT and MSUS median scores were 6 and 9, respectively. For each 5-point OMERACT and MSUS score increase, the risk of frequent gout attack increased 1.13-fold and 1.27-fold, respectively. The area under the curve (AUC) for the OMERACT and MSUS score was 0.654 (95% confidence interval [CI] 0.617-0.691) and 0.699 (95% CI: 0.663-0.735), respectively, (AUC difference 0.046, P-value for AUC difference, 0.013). Conclusions: The OMERACT and MSUS score were significantly associated with the risk of frequent gout attacks. The MSUS score outperformed the OMERACT in terms of frequent gout attack discrimination. Disclosure S.Yang: None. X.Lin: None. Y.Gao: None. N.Liang: None. Y.Han: None. H.Sun: None. S.Qu: None. H.Chen: None. Funding Key Technologies Research and Development Program of China (2019YFA0904500); National Natural Science Foundation of China (81870606, 82170904); Three-Year Action Plan (2022-2024) to Promote Clinical Skills and Innovation in Municipal Hospitals of Shanghai

#3191 RISK OF CKD IN LUPUS NEPHRITIS: CORRELATION WITH DURATION OF REMISSION AND DEVELOPMENT OF RENAL AND EXTRARENAL FLARES

Abstract Background and Aims Achievement of remission and prevention of SLE flares are important therapy targets in patients with SLE in order to avoid the development of systemic chronic damage. In patients with lupus nephritis, the correlation between the duration of remission, the occurrence of SLE flares and the development of CKD is unclear. The aims of this study are to investigate a) the risk of CKD in patients with lupus nephritis b) the correlation between the risk of CKD and the development of renal and extrarenal SLE flares c) the correlation between the risk of CKD and the achievement and duration of remission d) the probability and predictors of renal and extrarenal remission. Method This is a retrospective multicentric study of prospectively collected data. Patients were included if they were >18 years old, they had a histological diagnosis of lupus nephritis and they had at least 5 years of follow up after the diagnosis. CKD was defined as eGFR <60 ml/min/1.73m2 without active urinary sediment for at least 3 months. Remission was defined as normal renal function (serum creatinine <1.0 mg/dl, eGFR >60 ml/min/1.73m2), proteinuria <0.5 g/24h and cSLEDAI = 0 for at least 1 year. The probability of developing flares and achieving remission was estimated using Cox regression analysis. Results CKD developed in 57 patients out of the 303 included in the study (18.8%) during a median follow-up of 14.8 years. During the observation 257 patients achieved remission in a median time of 1.4 (0.7-3.6) years, while 46 patients never achieved it. 115 patients maintained remission until the end of follow-up (9.5 (5.8-14.5) years), while 142 developed a flare after a median time of 3.6 (2.3-5.9) years from the beginning of remission. Altogether, in these 142 patients, 174 SLE flares developed during a median follow-up of 17.8 (13.3-24.2) years: 132 renal flares (20 with serum creatinine increase, 112 with proteinuria) and 42 extra-renal flares. CKD developed in 11 patients with creatinine flares (55%), 19 patients with proteinuric flares (16.9%) and 1 patient with extra-renal flares (2.4%) (p<0.0001). The longer was the duration of remission, the lower the probability that remission was interrupted (Figure 1A) by the development of a SLE flare: the risk of flare reduced from 10% when the remission lasted less than 5 years, to 5% if the remission lasted 5-10 years and to 2% if the remission lasted more than 10 years (Figure 1B). CKD developed in 26 out of the 46 patients who never achieved remission (56%), in 31 patients among those who achieved remission but developed SLE flares (21.8%) and in none among those who maintained remission until the end of the observation (p<0.0001). We found that 3 years of persistent remission significantly reduced the risk of CKD development (Figure 2). At multivariate Cox regression analysis, age >40 years (OR: 1.017; 95% CI: 1.005-1.028; p = 0.004), therapy with hydroxychloroquine (OR: 1.384; 95% CI: 1.109-1.661; p = 0.021) and absence of arterial hypertension (OR: 0.699; 95% CI: 0.425-0.975; p = 0.011) were independent predictors of remission. Conclusion in patients with lupus nephritis, the risk of CKD is significantly higher if renal-extrarenal remission is not achieved or if it is interrupted by SLE flares. In particular, the risk of CKD is very high in patients who develop renal flares with creatinine increase. A longer duration of remission is related to a lower risk of SLE flares and of CKD: in particular, 3 years of remission protect from the development of CKD. Age older than 40 years, therapy with hydroxychloroquine and absence of arterial hypertension are associated with the achievement of remission.

#3830 TRAINED INNATE IMMUNITY IN RESPONSE TO NUCLEAR ANTIGENS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune disease directed against nuclear antigens, including those derived from apoptotic microparticles (MPs) and neutrophil extracellular traps (NETs). Innate immune cells display an hyperreactive phenotype in patients with SLE, with increased expression of immunostimulatory surface markers and increased production of proinflammatory cytokines. We hypothesize that the hyperreactive phenotype of innate immune cells in SLE is caused by the induction of trained immunity. Trained immunity is a de facto innate immune memory elicited by an initial stimulus that induces metabolic and epigenetic changes and results in a more vigorous inflammatory response to subsequent stimuli. Here we aim to investigate whether nuclear autoantigens derived from MPs and NETs can induce trained immunity in SLE patients. Method To investigate the capability of MPs and NETs to induce trained immunity we stimulated healthy PBMCs with isolated NETs and MPs or with plasma from SLE patients for 24 hours, washed and rested the cells for five days. Cells were restimulated with lipopolysaccharide (LPS) and Pam3CSK4. To test the activation status of innate immune cells, PBMCs were isolated from patients with SLE and healthy controls and stimulated the cells with different TLR agonists. Cytokine production was measured using ELISA. Immune cell subsets in SLE patients were analyzed by flow cytometry. We performed RNA sequencing and Chromatin immunoprecipitation (ChIP) sequencing for histone 3 lysine 4 trimethylation (H3K4me3) on monocytes from SLE patients and healthy controls. Results We found that in vitro both MPs and NETs, as well as plasma from SLE patients, can induce trained immunity. Initial stimulation with MPs, NETs or SLE plasma resulted in increased production of Tumor necrosis factor (TNF) and Interleukin (IL) 6 upon restimulation with different TLR agonists. Assessment of circulating immune cells showed higher percentages of monocytes in SLE patients compared to healthy controls, and we found that circulating monocytes from SLE patients produce increased levels of pro-inflammatory cytokines (IL-6, IL-1ß, TNF) after stimulation with Toll-like receptor agonists, indicating trained immunity. This is accompanied by increased expression of metabolism and inflammation-related genes, underscoring the hyperreactive phenotype typical in trained innate immune cells. Epigenetic analysis of monocytes revealed major changes in H3K4me3, an epigenetic mark associated with trained immunity. Conclusion Our findings provide new insight into the pathogenesis of SLE by showing that trained immunity can be elicited by SLE-related antigens present in MPs and NETs, and demonstrating that that circulating monocytes from SLE patients have a trained immunity phenotype. Trained immunity yields a possible biomarker for the risk of SLE flares and offers a new potential target for developing therapeutic strategies.

#2898 UNMET NEEDS AND POOR LONG-TERM RENAL OUTCOMES IN EUROPEAN PATIENTS WITH LUPUS NEPHRITIS

Abstract Background and Aims Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), associated with substantial morbidity and increased risk of end-stage renal disease (ESRD). Despite currently used therapies, a notable proportion of patients may not achieve sustained remission, leading to adverse disease outcomes. This study aims to summarize evidence on the long-term outcomes, burden of comorbidities, and real-world (RW) effectiveness of therapy in European patients with LN. Method A targeted literature review was conducted using MEDLINE/Pubmed and Embase to identify studies in patients with LN. Search strategies were developed for each database to identify relevant peer-reviewed articles published in English from March 2012 - March 2022 and conference abstracts from 2019 – March 2022. All records were screened according to pre-specified inclusion/exclusion criteria. Only studies conducted in a European setting were summarized here. Results Of 4,216 total records, 55 studies reported long-term outcomes of LN and RW effectiveness of treatment in European adults. Up to 36% of patients with SLE developed LN, and nearly all LN cases occurred within 5 years of SLE diagnosis. Patients with LN often suffered from serious infection (19-35%), cardiovascular disease (CVD) (26%), chronic kidney disease (CKD)/ESRD (6-22%) and were more likely to experience cardio- and cerebrovascular events than patients with SLE only (p = 0.001). Patients with LN had a higher risk of mortality compared to those with SLE only or other lupus manifestations (p<0.001), and deaths were often due to infections (8-32%), CVD (22-58%), or malignancies (5-27%). CKD/ESRD also contributed to poor survival – patients with ESRD had 3-times higher risk of death compared to those with LN only (p<0.001). The majority of RW studies evaluated effectiveness of standard of care (SOC) induction and/or maintenance therapy, mostly with mycophenolate mofetil and cyclophosphamide. Treatment response rates varied across the studies likely due to heterogeneity in study design, drug dosing, and patient population; comparative studies did not find significant differences in response rates between the regimens. Overall, 30-86% of patients with LN achieved complete renal response/remission (CRR) within the first year of starting SOC therapy. However, one study reported that only 38% of patients maintained CRR while on SOC over a 5-year period, suggesting inadequate long-term maintenance on existing therapies. Patients who were non-responders (NR) after 1 year had a significantly increased risk of mortality and CKD compared to responders (p<0.005). Patients achieving CRR had significantly longer CKD-free survival compared to NR at 15 years (95% vs 55%, p<0.0001), further highlighting the value of achieving response in terms of long-term renal outcomes. Despite initial response to current therapies, 20-35% of patients experienced a renal relapse/flare while on maintenance therapy, with one study noting significantly increased risk of proteinuric flares with azathioprine compared to other maintenance therapies (p = 0.01). Limited studies focused on treatment-experienced/refractory patients, with the majority evaluating rituximab (RTX)-based regimens. After one year of therapy, 29-64% of patients with refractory LN and 35% of patients with active LN despite SOC achieved CRR on RTX or belimumab, respectively. Conclusion European adults with LN have considerable comorbidity burden and poor long-term renal outcomes. Few patients achieve and maintain remission on SOC, and a notable proportion of patients experience renal relapse despite initial response to therapy. Given the impact that achieving CRR has on long-term outcomes, there is a need for effective therapies that provide sustained remission, especially for patients with severe/refractory LN.

Australian recommendations on perioperative use of disease-modifying anti-rheumatic drugs in people with inflammatory arthritis undergoing elective surgery.

Disease-modifying anti-rheumatic drugs (DMARDs) are effective treatments for inflammatory arthritis but carry an increased risk of infection. For patients undergoing surgery, there is a need to consider the trade-off between a theoretical increased risk of infection with continuation of DMARDs perioperatively versus an increased risk of disease flare if they are temporarily withheld. We used the Grading of Recommendations Assessment, Development and Evaluation methodology to develop recommendations for perioperative use of DMARDs for people with inflammatory arthritis undergoing elective surgery. The recommendations form part of the National Health and Medical Research Council-endorsed Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis. Conditional recommendations were made against routinely discontinuing conventional synthetic and biologic (b) DMARDs in the perioperative period but to consider temporary discontinuation of bDMARDs in individuals with a high risk of infection or where the impact of infection would be severe. A conditional recommendation was made in favour of temporary discontinuation of targeted synthetic DMARDs in the perioperative period.

SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.

Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

Monosodium urate crystals alter the circadian clock in macrophages leading to loss of NLRP3 inflammasome repression: Implications for timing of the gout flare.

Gout is caused by monosodium urate (MSU) crystal deposition within joints. This leads to acute episodes of inflammation ("gout flares") driven by NLRP3 inflammasome activation in macrophages. Gout flares are frequently present during late night/early morning. The reason for this timing is unclear. Recent evidence suggests the NLRP3 inflammasome is under circadian control. The purpose of this study was to determine whether MSU crystals cause changes in the circadian clock in macrophages leading to time-of-day differences in NLRP3 inflammasome activation. Levels of circadian clock components were measured in undifferentiated "monocytic" and PMA-differentiated "macrophagic" THP-1 cells cultured with/without MSU crystals. Caspase-1 activity was measured to assess NLRP3 inflammasome activity. MSU crystal exposure resulted in minimal effects on clock genes in THP-1 monocytes but BMAL1, CRY1, PER2, and REV-ERBα showed altered expression with reduced protein levels of BMAL1 and REV-ERBα in THP-1 macrophages. REV-ERBα activation or BMAL1 over-expression resulted in reduced MSU crystal-induced caspase-1 activity. BMAL1 knockdown resulted in a further increase in MSU crystal-induced caspase-1 activity, but only at times of day when BMAL1 levels were naturally high. MSU crystal-induced NLRP3 inflammasome activation was greatest at the time of day when BMAL1 levels were naturally low. MSU crystals alter the expression of circadian clock components in THP-1 macrophages leading to loss of BMAL1 and REV-ERBα-mediated repression of NLRP3 inflammasome activity and time-of-day differences in susceptibility to inflammasome activation. Our findings suggest that the nocturnal risk of gout flare is at least partially a consequence of altered circadian control of immune cell function.

E075 Predictive factors for successful biologic disease-modifying anti-rheumatic drugs dose tapering in rheumatoid arthritis

Abstract Background/Aims Use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) have revolutionised the management of rheumatoid arthritis (RA). However, their use is not without side effects including infection and malignancy risk. Recent EULAR and ACR guidelines support consideration of dose tapering in patients in sustained remission. This study looks at identifying predictive factors for successful bDMARD dose tapering, to help select patients who may benefit from it, whilst minimising the risk of flare. Methods We searched our local biologic database retrospectively for RA patients who were dose tapered in line with our local guideline, between June 2015 and December 2021. 91 patients were identified, 17 patients were excluded due to death or cessation of bDMARD for unrelated reasons. Clinical and demographic data collected included: age, gender, rheumatoid factor and/or anti-cyclic citrullinated peptide antibody positivity, biologic choice, concurrent use of conventional synthetic DMARD (csDMARD), number of previous bDMARDs, and overall annual cost-saving. Incidence of flares after tapering and outcome after resuming original dose of biologic were noted. Results Of the 74 patients included, 39 (53%) were on rituximab, 14 (19%) were on etanercept , 11 (15%) were on certolizumab pegol, 9 (12%) were on adalimumab, and 1 (1%) was on tocilizumab. The incidence of flare is highest in the first 6 months after being tapered (47%; n = 18). Of those who flared (n = 38), 84% regained control following re-introduction of original dose. After tapering, 67% (n = 18/27) of patients aged 70-89 remained in remission whilst more than 50% (n = 29/47) flared in younger age groups. Patients on rituximab were more likely to remain in remission. There were no notable differences in gender, seropositivity and concurrent csDMARD use. Despite reduced cost of biologics through use of biosimilars, we are estimated to save £68,783 per annum from dose tapering. Conclusion We find that patients in older age group or on rituximab have a higher chance of remaining in remission following bDMARD dose tapering. The risk of flare is not affected by gender, seropositivity or concurrent csDMARDs use. If patients were to flare post dose tapering, this is more likely to occur within the first 6 months after tapering. Disclosure M. Loh: None. C.J. Jones: Other; Received payment from Fresenius Kabi for participation in a focus group regarding publication of NICE TA 715. A. Peall: None. J. Trickey: None.

E056 C-reactive protein rise in rheumatology patients following COVID-19 vaccination

Abstract Background/Aims With widespread implementation of COVID-19 vaccine, there has been concern that it would trigger an immune activation due to its immunogenic properties. There is low-level evidence that patients with rheumatological diagnosis often have a disease flare following COVID-19 vaccination which not only has personal health implications but also wider socioeconomic implications. Inflammatory arthritis patients are classified as vulnerable patients requiring booster vaccinations. Therefore, there is a need to ascertain whether there is a risk of disease flare in this group of patients so as to counsel them appropriately in order to ensure flares are managed in timely manner. This study aims to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 30 days of receiving a COVID-19 vaccine using CRP as a surrogate marker. Methods A retrospective notes review was conducted of patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients that were currently on a disease-modifying anti-rheumatic drug (DMARD) or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination system (NIVS) and C-reactive protein (CRP) within 30 days of their vaccination. Results 1620 adults were identified from DAWN databases (mean age 61 years, 64% female). Three types of vaccination were used: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542/1620 (95.2% 1st dose), 1550/1620 (95.7% 2nd dose) and 1437/1620 (88.7% 3rd dose). 192/1542 patients (12.5%) had a CRP rise of greater than 10mg/L within 30 days of their vaccine, which was higher than baseline flare rate of 8.6% (p = 0.0004). Conclusion Patients with inflammatory arthritis and on DMARDS have high uptake of COVID-19 vaccine (95%) which is greater than the national average. A CRP rise greater than 10mg/L within 30 days of vaccination was observed in roughly 1 in 10 patients in our study population on all three doses which is consistent with other studies in the literature. Our results show statistically significant increase in the rate of disease flare (12.5% compared with baseline rate of 8.6%). However, SARS-CoV-2 infection has been shown many times to be an independent risk factor for rheumatic disease flare ranging from 20-40%. Therefore, patients with inflammatory arthritis should still be encouraged to receive COVID-19 vaccination. To maintain high levels of vaccine uptake, it is important to ensure that patients are aware of the risks of vaccinations and sufficiently safety netted so flares are managed early. As on-going booster vaccinations are planned for rheumatology patients, we recommend further research to better inform and counsel our patients. Furthermore, this study calls for diligence in monitoring patients with inflammatory arthritis for disease flare and for swift intervention to prevent losing disease control. Disclosure S. Kim: None. S. Gor: None. K. Yein: None. J. Michael: None. E. Price: None.

P013 A three-year audit of dose tapering biologic medications in a rheumatology service

Abstract Background/Aims Dose tapering of biologic therapies is supported by both ACR and EULAR guidelines. Identification of appropriate patients may deliver cost savings whilst minimising the risk of disease flare. To audit dose tapering activity for patients treated with bDMARD for rheumatoid (RA), psoriatic arthritis (PsA) and ankylosing spondylosis (AS) meeting locally agreed criteria over three years. Methods All patients treated with a bDMARD for RA, PsA or AS fulfilling criteria for dose tapering between 1st October 2019 - 1st October 2021 were identified from electronic health records (EHR). Rituximab patients were excluded due to reactive treatment responding to flare. Patients were required to have been on their bDMARD for = &amp;gt; one year, not prescribed oral steroids / treated with parenteral steroids in the past six months, no swollen joints in the past six months, and not failed dose tapering in the previous year. RA patients were ineligible if DAS ≥3.2 in the previous year; PsA if their biologic was prescribed by dermatology /active psoriasis; AS patients if BASDAI score of &amp;gt; 4 in past year. Records were flagged to prompt a shared decision-making discussion between the treating clinician and patient during routine appointments; additional patients were identified through clinical assessment. Failing dose tapering was defined as a post tapering flare requiring dose increase within one year. Patients were tapered by increasing the interval of a bDMARD. Results The number of patients that dose tapered increased from 24 in 2019 to 51 in 2021, making a total estimated NHS list saving of up to £170,000 per annum. (Table 1). Tapering was unsuccessful for 7/116 (6%) due to post tapering flares. Patients flaring after tapering were reassessed urgently and had their bDMARD dose reviewed. More patients were eligible than identified from EHR search due to missing data in coding; 787 (61%) across all years. Conclusion Dose tapering was well tolerated in eligible patients making this a safe and acceptable initiative. Use of EHR data and behavioural prompts for clinicians supported this in practice. Cost savings were reinvested to increase pharmacy support for homecare prescription management. Disclosure H. Light: None. J. Firth: None. J. Bluett: Grants/research support; JB has received a research grant from Pfizer. Other; JB has received travel/conference fees from UCB, Pfizer and Eli Lilly. K. Kinsey: None.

Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

COVID-19 vaccination experience in patients with rheumatoid arthritis treated at a single VA medical center

BackgroundFollowing the introduction of the COVID-19 vaccines, there has been uncertainty as to whether receiving the COVID-19 vaccine will result in overactivation of the immune system and subsequently lead to an autoimmune disease flare.The purpose of this study was to assess whether rheumatoid arthritis (RA) patients who received the mRNA COVID-19 vaccine are at increased risk for disease flare. MethodsWe conducted a single-center retrospective and prospective study at the Louis Stokes Cleveland VA Medical Center between 12/2021 and 2/2022. We included 100 patients with rheumatoid arthritis (RA) who were actively on immunosuppressive therapy and received three doses of thePfizer-BioNTech vaccine. A survey questionnaire was used to collect data about their RA and if they developed symptoms post vaccination. Our primary end point was to determine incidence of flare of RA after COVID-19 vaccine. Secondary end points were to estimate the side effect profile from the vaccine, and to check if patients developed a COVID-19 infection after they received the vaccine. ResultsNone of the patients reported symptoms of RA flare within two months of receiving the 3 doses of the vaccine. Most common vaccine side effects were soreness over the injection site (n = 14), headache (n = 11), fatigue(n = 7) and myalgias(n = 4). 5 patients developed a COVID-19 infection prior to receiving the vaccine, 8 after being vaccinated, 3 of the 8 within 5 months from the second dose and 5 out of the 8 within 3 months from the third vaccine dose. ConclusionRA patients receiving the COVID-19 Pfizer mRNA vaccine do not appear to commonly develop major symptoms, flares or side effects following the vaccine. Further research with larger numbers of patients with rheumatoid arthritis as well as those with other autoimmune disease is needed to better understand the safety and effectiveness of COVID-19 vaccine.

Identification of biomarkers that predict renal flare in childhood-onset lupus nephritis with mycophenolate acid.

Children-onset lupus nephritis (cLN) occurs>50% of patients with systemic lupus erythematosus. Mycophenolic acid (MPA) is the first-line agent for the induction and maintenance treatment of LN. This study was to explore the predictors of renal flare in cLN. Data from 90 patients were included in population pharmacokinetic (PK) models to predict MPA exposure. Cox regression models and restricted cubic spline were performed in 61 patients to identify the risk factors for renal flare, baseline clinical characteristics and MPA exposures as potential covariates. PK best fitted a two-compartment model of first-order absorption and linear elimination, with delayed absorption. Clearance increased with weight and immunoglobulin G (IgG), but decreased with albumin and serum creatinine. During follow-up of 1040 (658-1359) days, 18 patients experienced a renal flare, after a median time of 932.5 (663.5-1316) days. Each 1-mg·h/L increase of MPA-AUC was associated with a 6% decreased risk of an event (HR=0.94; 95% CI: 0.90-0.98), while IgG significantly increased this risk (HR=1.17; 95% CI: 1.08-1.26). ROC analysis showed that MPA-AUC0-12h<35mg·h/L and IgG>17.6g/L had a good prediction of renal flare. Of restricted cubic spline, the risk of renal flares decreased with higher MPA exposure but reached a plateau when AUC0-12h>55mg·h/L, while substantially increases when IgG is>18.2g/L. Monitoring MPA exposure together with IgG could be very useful during clinical practice to identify patients with a potential high risk of renal flare. This early risk assessment would allow for the treat-to-target and tailored medicine.

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.

Discontinuation of Conventional Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis and Excellent Disease Control

This open-label randomized clinical trial assessed the 12-month risk of disease activity flares after discontinuation of conventional synthetic DMARDs (csDMARDs) compared with continuing half-dose csDMARDs in adult Norwegian patients with rheumatoid arthritis and excellent disease control.

Do different platforms of coronavirus vaccines have different impacts on psoriasis flares?

This study evaluated the impacts on psoriasis flares of 3 vaccine platforms: inactivated, viral vector and mRNA. Respectively, 198 and 96 psoriasis patients with and without COVID-19 vaccination during the study period. Group comparison revealed no increased risk of psoriasis flaring after COVID-19 vaccination. The vaccinated group received 425 doses of vaccine (140 inactivated, 230 viral vector and 55 mRNA). Patients' self-reported symptoms included all three platforms causing psoriasis flare, but the highest was among patients administered with mRNA vaccines. Most flares were mild to moderate, and most patients (89.8%) managed their flare-up lesions without rescue therapy. In conclusion, our study showed that the rate of psoriasis flare was not significantly different between vaccinated and unvaccinated groups. Factors that might explain psoriasis flare include vaccine-related psychological stress and side effects from vaccination. Different platforms of corona vaccines seemed to have different impact of psoriasis flares. Based on our results and the recommendations of several consensus guidelines, the benefits of COVID vaccinations outweigh the risks to patients with psoriasis. Patients with psoriasis should receive a COVID vaccine as soon as one is available.

Pregnancy and medications for inflammatory bowel disease: An updated narrative review.

Inflammatory bowel disease (IBD) is often diagnosed during the peak reproductive years of young women. Women with active IBD around conception are at a significantly increased risk of disease relapse during pregnancy, which is associated with poor pregnancy and neonatal outcomes. Given these substantial risks, it is prudent that disease remission should ideally be achieved before conception. Unfortunately, some patients may experience a disease flare-up even if they are in a state of remission before pregnancy. Patients must continue their IBD medications to reduce the risk of disease flare and subsequent poor outcomes during the gestational and postpartum periods. When treating IBD flare-ups during pregnancy, the management is quite similar to the therapeutic approach for non-pregnant patients with IBD, including 5-aminosalicylate, steroids, calcineurin inhibitors (CNIs), and biologic therapies. While the data regarding the safety of CNIs in pregnant women with IBD is limited, the findings in our recent meta-analysis suggest that CNIs may be safer to use in those with IBD than in solid organ transplant recipients. There are several types of biologics and small-molecule therapies currently approved for IBD, and physicians should thoroughly understand their clinical benefits and safety profiles when utilizing these treatments in the context of pregnancy. This review highlights recent studies, including our systematic review and meta-analysis, and discusses the clinical advantages and safety considerations of biologics and small molecules for pregnant women with IBD.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: a prospective Chinese cohort study.

Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment (P = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Incidence, features and outcome of disease relapse after COVID-19 vaccination in patients with idiopathic inflammatory myopathies.

Vaccination against coronavirus disease (COVID-19) is relatively safe in patients with idiopathic inflammatory myopathies (IIM), however, myositis flares following vaccination have been poorly studied. We aimed to evaluate the frequency, features and outcomes of disease relapses in patients with IIM following COVID-19 vaccination. A cohort of 176 IIM patients were interviewed after the 3rd wave of the COVID-19 pandemic and followed prospectively. Relapses were determined using the disease state criteria and the outcome of the flares with myositis response criteria, calculating the total improvement score (TIS). A total of 146 (82.9%) patients received a vaccination, 17/146 (11.6%) patients had a relapse within 3 months, and 13/146 (8.9%) patients within one month. The relapse rate of unvaccinated patients was 3.3%. Three months after the post-vaccination relapses, 70.6% of the patients (12/17) achieved an improvement of disease activity (average TIS score: 30±15.81; 7 minor, 5 moderate and 0 major improvements). Six months after flares improvement was detected in 15/17(88.2%) of relapsed patients (average TIS score: 43.1±19.53; 3 minimal, 8 moderate and 4 major). Forward stepwise logistic regression analysis revealed that the active state of myositis at the time of injection (p<0.0001; OR:33; CI:9-120) was significantly associated with the occurrence of a relapse. A minority of the vaccinated IIM patients had a confirmed disease flare after COVID-19 vaccination and the majority of the relapses improved after individualized treatment. An active disease state at the time of vaccination probably contributes to the increased risk of a post vaccination myositis flare. This article is protected by copyright. All rights reserved.

Safety considerations for withdrawal of nucleos(t)ide analogues in patients with chronic hepatitis B: First, do no harm.

Nucleos(t)ide analogues (NA) are widely used to treat hepatitis B virus (HBV) infection, but they cannot eradicate the virus and treatment duration can be lifelong if the endpoint is set at seroclearance of the hepatitis B surface antigen (HBsAg). As an alternative strategy, finite NA therapy without the prerequisite of HBsAg seroclearance has been proposed to allow treatment cessation in patients with sustained undetectable HBV viremia for two to three years. However, reactivation of viral replication almost always follows NA withdrawal. Whereas HBV reactivation might facilitate HBsAg seroclearance in some, it could lead to serious acute flare-ups in a certain proportion of patients. Occurrence and consequences of NA withdrawal flares are complicated with various factors involving the virus, host, and treatment. Accurate risk prediction for severe flares following NA cessation is essential to ensure patient safety. The risks of life-threatening flares in patients who discontinued NA according to the stopping rules of current guidelines or local reimbursement policies have recently been quantitatively estimated in large-scale studies, which also provided empirical evidence to help identify vulnerable patients at risk of devastating outcomes. Moreover, risk predictors were further explored and validated to hopefully aid in patient selection and management. In this narrative review with a focus on patient safety, we summarize and discuss current literature on the incidence of severe flares following NA cessation, risk stratification for candidate selection, rules of posttreatment monitoring, and indications for treatment resumption. We also share our thoughts on the limitations of existing knowledge and suggestions for future research.