Prevention Of Flares Research Articles

#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.

P170 Identifying predictors of axial spondyloarthritis flare onset using daily patient-reported data collected via a smartphone app

Abstract Background/Aims Smartphone apps for self-tracking symptoms and behaviour can offer novel insights into axial spondyloarthritis (axSpA) self-management and the experience of flares. Previous studies have predicted weekly flare occurrence in axSpA using physical activity data, and weekly flare occurrence in other rheumatic diseases using symptom data. However, no study has yet used daily flare, symptom and behaviour data to predict flare onset. The aims of this study were to examine the association between daily self-reported symptom and behaviour data with axSpA flare onset using data collected via a smartphone app. Methods A secondary analysis of 136 participants (Mage=52, 70% male) used clinical data collected at the Royal United Hospital for Rheumatic Diseases (Bath) and daily self-tracking data collected via the Project Nightingale smartphone app from 2018-21. Self-tracking data for 8 daily and 13 optional symptoms were scored on a 5-point scale. Participants recorded daily whether an axSpA flare started, continued, stopped or there was no flare. Paired t-tests were used to examine differences in symptoms during flare compared to non-flare days. A mixed effects binary logistic regression model was computed, with flare onset as the binary outcome, participant ID as the random effect, and the change (difference) in each symptom score from the preceding day as fixed effects. Odds ratios (OR) are reported to indicate the increased likelihood of flare onset given a one-point change in symptom score. Results Periods of flare were associated with greater anti-inflammatory use, lower confidence in self-management, more fatigue, worse mood, more pain, reduced exercise, worse sleep quality, and greater stress (p<.001), and lower adherence, more frequent chest pain, more hot flushes and greater impact of the menstrual cycle (p<.01) compared to periods without flare. The predictive model found that changes in certain symptoms and behaviours from the day preceding flare were associated with higher likelihood of flare onset: increased pain score (OR = 3.13, 95% CI [2.70, 3.70]), fatigue score (OR = 1.28, 95% CI [1.15, 1.43]) and anti-inflammatory use (OR = 1.25, 95% CI [1.08, 1.45]), and decreased amount of exercise (OR = 1.16, 95% CI [1.05, 1.30]). Conclusion This is the first study to use daily flare and symptom data to predict flare occurrence. Increases in pain, fatigue and anti-inflammatory use and decreased exercise from the day preceding flare significantly increased the likelihood of flare onset. Potential future integration of predictive flare features into smartphone apps for disease self-management could contribute to more effective prevention and targeting of imminent flares, to enhance individuals’ self-efficacy, disease outcomes and quality of life. Critically, such app development will require consideration of the needs and perspectives of people living with axSpA for optimal user experience. Disclosure A. Kypta-Vivanco: None. R. Barnett: None. R. Sengupta: Honoraria; Dr. Raj Sengupta has received honoraria or consultancy fees from Abbvie, Biogen, Novartis, Celgene, Lilly, Chugai, MSD and UCB. Grants/research support; Dr. Raj Sengupta has received grants/ research support from AbbVie, Celgene, Novartis and UCB. Other; Dr Raj Sengupta is also on the advisory boards for AbbVie, Biogen, Chugai, Lilly, Novartis and UCB.

Nutritional factors in the prevention and treatment of gout

Introduction and purpose: Despite the fact that effective urate lowering therapy and anti-inflammatory drugs for the treatment of gout are commonly available, there is considerable interest in novel treatment approaches. Gouty patients often have a multitude of comorbidities, which lead to concern over drug–drug interactions and medication adverse events. Thus, diet modifications are examined as a way of nonpharmacological treatment of gout. In this review, we explore the potential impact of nutritional factors on hyperuricemia and clinical gout outcomes. A search was conducted using PubMed and Google Scholarship databases.
 Brief description of the state of knowledge: Management in patients with gout should be holistic. Incorrect nutrition may lead to hyperuricemia. Studies to date suggest that avoidance of certain foods and beverages can decrease the frequency of gout flares. Weight loss may be beneficial for prevention as well as treatment of gout and its comorbidities. The impact of various types of diet on the course of gout has been given particular attention and recent research suggests that vegetarian, mediterranean and dash diets may be beneficial for gouty patients. Also, some vitamins and omega-3 PUFA have favorable effects and the potential clinical use in gout treatment.
 Conclusions: We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients. Although piecemeal modifications of various nutrients often provide incomplete dietary recommendations, understanding the role of nutritional factors in gout development would be helpful for patients in choosing their healthy diet.

Reset of Inflammatory Priming of Joint Tissue and Reduction of the Severity of Arthritis Flares by Bromodomain Inhibition.

We have recently shown that priming of synovial fibroblasts (SFs) drives arthritis flares. Pathogenic priming of SFs is essentially mediated by epigenetic reprogramming. Bromodomain and extraterminal motif (BET) proteins translate epigenetic changes into transcription. Here, we used a BET inhibitor (I-BET151) to target inflammatory tissue priming and to reduce flare severity in a murine experimental arthritis model. BALB/c mice were treated by intraperitoneal injection or by local injection in the paw with I-BET151, which blocks the interaction of BET proteins with acetylated histones. We assessed the effects of I-BET151 on acute arthritis and/or inflammatory tissue priming in a model of repeated injections of monosodium urate crystals or zymosan into the mouse paw. I-BET151 was given before arthritis induction, at peak inflammation, or after healing of the first arthritis bout. We performed transcriptomic (RNA-Seq), epigenomic (ATAC-Seq), and functional (invasion, cytokine production, migration, senescence, metabolic flux) analyses of murine and human SFs treated with I-BET151 in vitro or in vivo. Systemic I-BET151 administration did not affect acute inflammation but abolished inflammatory tissue priming and diminished flare severity in both preventive and therapeutic treatment settings. I-BET151 was also effective when applied locally in the joint. BET inhibition also inhibited osteoclast differentiation, while macrophage activation in the joint was not affected. Flare reduction after BET inhibition was mediated, at least in part, by rolling back the primed transcriptional, metabolic, and pathogenic phenotype of SFs. Inflammatory tissue priming is dependent on transcriptional regulation by BET proteins, making them promising therapeutic targets for prevention of arthritis flares in previously affected joints.

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.

Clinical aspects of cutaneous lupus erythematosus.

Lupus erythematosus (LE) is an autoimmune inflammatory disease with a wide clinical spectrum from life-threatening multi-organ inflammation in systemic lupus erythematosus (SLE) to limited skin disease in cutaneous LE (CLE). The etiology of CLE is still not fully understood but a multifactorial genesis with genetic predisposition and certain environmental factors as triggers for the development are generally accepted features. Lesions can be induced and aggravated by UV-irradiation and smoking is linked to more severe forms of skin disease and to co-morbidity. Drugs, including many common medicines like antihypertensives, are known to induce subacute CLE (SCLE). The mechanisms involved have recently been shown to be part of the IFN-I pathway and new, specific treatments are currently in clinical trials. CLE is currently classified in subtypes based on clinical presentation and duration into acute CLE (ACLE), SCLE, and chronic CLE (CCLE). Distinct subtypes can be seen in individual patients or coexist within the same patient. Because of the confluent and overlapping picture between these subsets, serology, and histopathology constitute an important role guiding towards correct diagnose and there is ongoing work to update the classification. The Cutaneous Lupus Area Severity Index (CLASI) is a validated tool to measure activity and damage both in clinical trials but also for the clinician to evaluate treatment and follow the course of the disease among patients. CLE is known to have substantial impact on the life of those affected. Several tools have been proposed to measure QoL in these patients, currently Skindex-29 is probably the most used. Patient education is an important part of prevention of flares, including UV-protection and smoking cessation. First-line treatment includes topical corticosteroids as well as topical calcineurin inhibitors with the addition of systemic treatment with antimalarials in more severe or therapy resistant cases. Treatment specifically targeting CLE has been lacking, however novel potential therapies are in later phase clinical trials. In this review we aim to describe the different subsets of the cutaneous form in LE with focus on clinical aspects.

Preventive plasmapheresis for rituximab related flare in cryoglobulinemic vasculitis

IntroductionRituximab monotherapy represents the main therapeutic option for cryoglobulinemic vasculitis (CV) with severe organ involvement. However, initial worsening of the CV, known as rituximab-associated CV flare (=CV flare), has been described and are associated with high mortality rates. The aim of the present study is to evaluate the outcomes of plasmapheresis initiated before or during rituximab treatment, as prevention of CV flare. MethodsWe conducted a retrospecttive study in our tertiary referral center from 2001 to 2020. We have included all patients with CV receiving rituximab and divided them in two groups whether they had flare prevention by plasmapheresis or not. We evaluated rituximab-related CV flare incidence in both groups. CV flare was defined as the onset of a new organ involvement or worsening of the initial manifestations within 4 weeks following rituximab. ResultsAmong the 71 patients included, 44 received rituximab without plasmapheresis (control = CT cohort) and 27 received plasmapheresis before or during rituximab treatment (preventive plasmapheresis = PP cohort). PP was given to patients thought to have a high risk of CV flare, with significantly more severe diseases than patients in the CT cohort. Despite this, no CV flare was observed in the PP group. In the other hand, 5 flares occurred in the CT cohort. ConclusionOur results show that plasmapheresis is efficient and well tolerated to prevent rituximab-associated CV flare. We believe that our data support the use of plasmapheresis in this indication, especially in patients with high risk of CV flare.

Efficacy and safety of adalimumab for inflammatory flare prevention in paediatric non-infectious anterior uveitis with peripheral retinal vascular leakage: a study protocol for a single-centre, randomised controlled trial

IntroductionPaediatric patients with chronic anterior uveitis are more prone to suffer from the chronic course of intraocular inflammation and adverse effects of long-term immunomodulatory therapy, either topical glucocorticosteroids or systemic...

Dexamethasone Coanalgesic Administration in Steroid Naïve and Steroid Non-Naïve Patients for the Prevention of Pain Flares after Palliative Radiotherapy for Bone Metastases.

Dexamethasone could be an effective prophylactic agent for the prevention of pain flares after palliative radiotherapy (RT) for uncomplicated bone metastases. To date, there are no data on its prophylactic coanalgesic (opioid-sparing) effect after RT in patients with complicated bone metastases compared to uncomplicated ones, which is the aim of our study. Twenty-nine American Society of Anaesthesiologists (ASA) III-IV patients, aged ≥18, treated with single-fraction 8 Gy/1 or multi-fraction 20 Gy/5 RT for painful uncomplicated bone metastases (steroid naïve patients, n = 14) or complicated ones (steroid non-naïve patients, n = 15), were examined retrospectively. All patients received parenteral dexamethasone (4 mg or 8 mg daily, 1 hour before RT, followed by the same dose for the next 4 days) along with their background and breakthrough pain opioid intake (morphine equivalents) during their 5-day in-hospital stay. Pain severity (numeric rating scale) and analgesic consumption were recorded at admission, daily during the hospital stay, and for 10 days following treatment. Binary logistic regression was used to determine predictive factors for pain flare occurrence. A higher ASA score is the only determinant positively influencing opioid consumption (P = 0.018) and pain flare as well (OR = 15.00; 95% CI: 2, 24-100, 48; P = 0.005). Lower dose 4 mg dexamethasone was revealed as a moderate analgesic agent in steroid naïve patients with no side effects, whereas in steroid non-naïve patients the predominantly higher dose 8 mg dexamethasone had minimal impact on pain flares prevention at the expense of more pronounced immunosuppression (P = 0.039). Irrespective of the supporting evidence of dexamethasone potential for prevention of RT-induced pain flare, our data failed to reveal its efficacy in the real practice world (a case mix of uncomplicated and complicated bone metastases). Further dose-effect bigger studies are needed, identifying optimal doses of dexamethasone intake and its optimal duration in high-risk patients.

When underlying biology threatens the randomization principle - initial gout flares of urate-lowering therapy.

Flare is the dominant feature of gout and occurs because of inflammatory response to monosodium urate crystals; prevention of gout flares should be the major goal of gout care. However, a paradoxical increase in the risk of flare following initiation of urate-lowering therapy presents considerable challenges for proving the expected long-term benefits of flare prevention in clinical trials. Nevertheless, excluding from enumeration flares that occur in the initial post-randomization period (which can last several months to 1 year) can threaten the core benefits of randomization: the characteristics of the remaining participants can differ from those who were randomized, introducing potential bias from confounding (both measured and unmeasured); participants who drop out or die are excluded from the analysis, introducing potential selection bias; and, finally, ignoring initial flares underestimates participants’ experience during the trial. This Perspective discusses these issues and recommends measures that will allow for high-level evidence that preserves the randomization principle, to satisfy methodological scrutiny and generate robust evidence-based guidelines for gout care.

Use of Dexpanthenol for Atopic Dermatitis-Benefits and Recommendations Based on Current Evidence.

Background: Atopic dermatitis (AD) is an inflammatory skin disease of multiple phenotypes and endotypes, and is highly prevalent in children. Many people of all ages, including active adolescents, pregnant women, and the elderly, suffer from AD, experiencing chronicity, flares, and unexpected relapse. Dexpanthenol has multiple pharmacological effects and has been employed to treat various skin disorders such as AD. We aimed to summarize the up-to-date evidence relating to dexpanthenol and to provide a consensus on how to use dexpanthenol effectively for the treatment of AD. Methods: The evidence to date on the application and efficacy of dexpanthenol in AD was reviewed. The literature search focused on dexpanthenol use and the improvement of skin barrier function, the prevention of acute flares, and its topical corticosteroid (TCS) sparing effects. Evidence and recommendations for special groups such as pregnant women, and the effects of dexpanthenol and emollient plus in maintenance therapy, were also summarized. Results: Dexpanthenol is effective and well-tolerated for the treatment of AD. Dexpanthenol improves skin barrier function, reduces acute and frequent flares, has a significant TCS sparing effect, and enhances wound healing for skin lesions. Conclusion: This review article provides helpful advice for clinicians and patients on the proper maintenance treatment of AD. Dexpanthenol, as an active ingredient in ointments or emollients, is suitable for the treatment and maintenance of AD. This paper will guide dermatologists and clinicians to consider dexpanthenol as a treatment option for mild to moderate AD.

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis.

BackgroundImproved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn’s disease (CD active).MethodsColonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.ResultsThe majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.ConclusionThis study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.

OA37 Secukinumab treatment in children and adolescents with enthesitis-related arthritis and juvenile psoriatic arthritis: efficacy and safety results from a Phase 3 study

Abstract Background/Aims Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two conditions that represent paediatric correlates of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively. Secukinumab has demonstrated efficacy and safety in adult patients with PsA, ankylosing spondylitis, and non-radiographic axSpA. This study evaluated efficacy and safety of secukinumab using a randomized, double-blind, placebo-controlled flare prevention design in patients with active ERA and JPsA. Methods Patients (aged 2 to < 18 years) classified as ERA or JPsA according to ILAR criteria of ≥ 6 months’ duration with active disease were included. The 2-year study consisted open-label subcutaneous secukinumab (75/150 mg in patients <50/ ≥50 kg) treatment at baseline, and at Weeks 1, 2, 3, 4, 8, and 12 in treatment period (TP) 1. Responders who achieved at least JIA ACR 30 response at Week 12 were randomized into the double-blind TP2 to continue secukinumab or placebo every 4 weeks until disease flare, or up to Week 100. Primary endpoint was time to flare in TP2; key secondary endpoints included JIA ACR 30/50/70/90/100, inactive disease, juvenile arthritis disease activity score (JADAS), enthesitis and active joint counts, and safety. Analysis of time to flare in TP2 included proportion of patients with disease flare, Kaplan-Meier estimate of median days for time to flare, hazard ratio (HR) estimate, and stratified log-rank test P-value. Intent-to-treat (ITT) analysis using non-responder imputation (NRI) and as-observed analysis were performed for JIA ACR 30/50/70/90/100 responses and inactive disease. Results 86/97 (88.7%) screened patients were enrolled in TP1 (mean age, 13.1 years; female, 33.7%; ERA, n = 52; JPsA, n = 34) with a mean JADAS-27 score of 15.1 and enthesitis count of 2.6 at baseline. At Week 12, 75/83 (90.4%) patients achieved JIA ACR 30 and entered TP2. There were 21 flares in placebo-treated and 10 flares in secukinumab-treated patients during TP2. Primary endpoint was met: secukinumab-treated patients had significantly longer time to flare versus placebo, resulting in a 72% reduced flare risk (HR: 0.28; 95% CI: 0.13-0.63; P<0.001). There were minor differences between the ITT and as-observed analysis in JIA ACR responses and inactive disease in TP1. Improvement in JADAS-27 score was observed in patients in both ERA and JPsA categories (mean JADAS-27 score of 4.6). Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in secukinumab and placebo groups were comparable in entire TP. No new safety signals were observed in patients receiving secukinumab (injection-site reaction, n = 1; overall patient-years=141.5). Conclusion In children and adolescents with ERA and JPsA, efficacy of secukinumab was demonstrated with significantly longer time to flare versus placebo, with sustained improvement of signs and symptoms up to Week 104. Efficacy was observed in ERA and JPsA patients along with a favorable safety profile. Disclosure A.V. Ramanan: Consultancies; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. Honoraria; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. H.I. Brunner: Consultancies; Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer. Member of speakers’ bureau; Pfizer, Roche, GlaxoSmithKline. Grants/research support; Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, Pfizer. I. Foeldvari: Consultancies; Novartis, Eli Lilly, Pfizer. E. Alexeeva: Member of speakers’ bureau; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. Grants/research support; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. N.A. Ayaz: None. I. Calvo: Consultancies; Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia. Member of speakers’ bureau; Sobi, Novartis, Novartis, GlaxoSmithKline, Pfizer, Amgen, Clementia. O. Kasapcopur: None. V.G. Chasnyk: None. M. Hufnagel: Grants/research support; Astellas, F. Hoffmann-La Roche, Novartis. Z. Zuber: None. G. Schulert: Consultancies; Sobi, Novartis. S. Ozen: None. A. Popov: None. C. Scott: None. B. Sözeri: None. E. Zholobova: Member of speakers’ bureau; Abbvie, Pfizer, Roche, Novartis. Grants/research support; Pfizer, Novartis. X. Zhu: Other; Employee of Novartis. S. Whelan: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Ravelli: Consultancies; AbbVie, Pfizer. Honoraria; AbbVie, Pfizer, Novartis, Reckitt-Benkiser, Angelini. Member of speakers’ bureau; Novartis. Grants/research support; Novartis, Pfizer. A. Martini: Consultancies; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. Honoraria; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. D.J. Lovell: Consultancies; AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie. Member of speakers’ bureau; Abbott, Novartis, DSMB member: Forest Research, NIH-NIAMS, Canadian Arthritis Society. N. Ruperto: Honoraria; Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.

Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis: results from the PREVENT-JIA trial

ObjectivesTo investigate the ability of high-sensitivity C-reactive protein (hsCRP) and S100A12 to serve as predictive biomarkers of successful drug withdrawal in children with clinical remission of juvenile idiopathic arthritis (JIA).MethodsThis...

Diagnosing and Managing Hidradenitis Suppurativa in Pediatrics

Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease that presents as exquisitely tender abscesses, draining fistulae, and sinus tracts. HS can lead to significant impairments in patients' quality of life, especially for children and adolescents who face challenges related to self-esteem and physical and emotional development. Severe long-term physical sequelae of inadequately treated HS include extensive scarring, urogenital strictures, immobility, and squamous cell carcinoma; emotional sequelae include depression, anxiety, and suicidal ideation. Many of the devastating long-term sequelae associated with HS can be prevented with early recognition and proper collaborative management. This article reviews strategies to aid pediatricians in early diagnosis of HS and provides clinical pearls for management and prevention of disease flares. [Pediatr Ann. 2022;51(3):e123-e127.].

Low-dose belimumab for patients with systemic lupus erythematosus at low disease activity: protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionSLE is a chronic inflammatory systemic autoimmune disease with relapsing–remitting pattern. B-lymphocyte stimulator was involved in the pathogenesis of SLE. The humanised monoclonal antibody belimumab with 10 mg/kg was effective...

Dietary supplements for chronic gout.

Dietary supplements are frequently used for the treatment of several medical conditions, both prescribed by physicians or self administered. However, evidence of benefit and safety of these supplements is usually limited or absent. To assess the efficacy and safety of dietary supplementation for people with chronic gout. We updated the original search by searching CENTRAL, MEDLINE, Embase, CINAHL, and four trials registers (August 2020). We applied no date or language restrictions. We also handsearched the abstracts from the 2010 to 2019 American College of Rheumatology and European League against Rheumatism conferences, and checked the references of all included studies. We considered all published randomised controlled trials (RCTs) or quasi-RCTs that compared dietary supplements with no supplements, placebo, another supplement, or pharmacological agents for adults with chronic gout for inclusion. Dietary supplements included, but were not limited to, amino acids, antioxidants, essential minerals, polyunsaturated fatty acids, prebiotic agents, probiotic agents, and vitamins. The major outcomes were acute gout flares, study withdrawal due to adverse events (AEs), serum uric acid (sUA) reduction, joint pain reduction, participant global assessment, total number of AEs, and tophus regression. We used standard methodological procedures expected by Cochrane. Two previously included RCTs (160 participants) met our inclusion criteria; we did not identify any new trials for this update. As these two trials evaluated different diet supplements (enriched skim milk powder (SMP) and vitamin C) with different outcomes (gout flare prevention for enriched SMP, and sUA reduction for vitamin C), we reported the results separately. One trial (120 participants), at unclear risk of selection and detection bias, compared SMP enriched with glycomacropeptides (GMP) with un-enriched SMP, and with lactose, over three months. Participants were predominantly men, aged in their 50s, who had severe gout. The results for all major outcomes were imprecise, except for pain. None of the results were clinically significant. The frequency of acute gout attacks, measured as the number of flares per month, decreased in all three groups over the three-month study period. The effects of enriched SMP (SMP/GMP/G600) compared with the combined control groups (SMP and lactose powder) at three months in terms of mean number of gout flares per month were not clinically significant (mean (standard deviation (SD)) flares per month: 0.49 (1.52) in SMP/GMP/G60 group versus 0.70 (1.28) in the control groups; absolute risk difference: mean difference (MD) -0.21 flares per month, 95% confidence interval (CI) -0.76 to 0.34; low-quality evidence). The number of withdrawals due to adverse effects was similar between groups (7/40 in SMP/GMP/G600 group versus 11/80 in control groups; (risk ratio (RR) 1.27, 95% CI 0.53 to 3.03); there were 4% more withdrawals in the SMP/lactose groups (10% fewer to 18% more; low-quality evidence). Serum uric acid reduction was similar across groups (mean (SD) -0.025 (0.067) mmol/L in SMP/GMP/G60 group versus -0.010 (0.069) in control groups; MD -0.01, 95% CI -0.04 to 0.01; low-quality evidence). Pain from self-reported gout flares (measured on a 10-point Likert scale) improved slightly more in the GMP/G600 SMP group compared with controls (mean (SD) -1.97 (2.28) in SMP/GMP/G600 group versus -0.94 (2.25) in control groups; MD -1.03, 95% CI -1.89 to -0.17). This was an absolute reduction of 10% (95% CI 20% to 1% reduction; low-quality evidence), which may not be of clinical relevance. The risk of adverse events was similar between groups (19/40 in SMP/GMP/G600 group versus 39/80 in control groups; RR 0.97, 95% CI 0.66 to 1.45); the absolute risk difference was 1% fewer adverse events (1% fewer to 2% more), low-quality evidence). Gastrointestinal events such as nausea, flatulence and diarrhoea were the most commonly reported adverse effects. Data for participant global assessment were not available for analysis; the study did not report tophus regression. One trial (40 participants), at high risk of selection, performance, and detection bias, compared vitamin C alone with allopurinol, and with allopurinol plus vitamin C, in a three-arm study. We only included data from the vitamin C versus allopurinol comparison in this review. Participants were predominantly middle-aged men, and their severity of gout was representative of gout in general. Allopurinol reduced sUA levels more than vitamin C (MD 0.10 mmol/L, 95% CI 0.06 to 0.15), low-quality evidence. The study reported no adverse events; none of the participants withdrew due to adverse events. The study did not assess the rate of gout attacks, joint pain reduction, participant global assessment, or tophus regression. While dietary supplements may be widely used for gout, this review found no high-quality that supported or refuted the use of glycomacropeptide-enriched skim milk powder or vitamin C for adults with chronic gout.

P065 A case of fibrodysplasia ossificans progressiva in Kenya

Abstract Background Fibrodysplasia Ossificans Progressiva (FOP) is an extremely rare and disabling disorder affecting 1 in 2 million individuals worldwide. It is caused by mutations in bone morphogenetic protein which leads to extra-skeletal ossification of soft tissues in a characteristic cranio-caudal pattern. Hallux valgus, episodic flares and progressive functional disability are characteristic features. The cause of death is often cardio-respiratory failure following thoracic insufficiency. The objective of our case study is to describe a rare but interesting case of fibrodysplasia ossificans progressiva (FOP) in an African setting. Methods This was a retrospective case review Results Two-year-old boy presented with painful firm masses of bony consistency over the axilla, neck, occiput and the forehead for seven months. He developed progressive inability to lift the arms, flex his neck and had a characteristic stiff posture while walking. The masses had a waxing and waning nature lasting about 4–5 days but with no complete resolution. He was previously treated with antibiotics for lymphadenitis which was diagnosed by biopsy of the neck mass at a different health facility. On examinationhe had bony masses on the posterior aspect of the neck tender on palpation and attached to the underlying subcutaneous tissue. Similar masses were found on his anterior and posterior chest wall measuring 1 cm by 1 cm anteriorly and larger masses- measuring 5 cm by 5 cm posteriorly. He had bilateral hallux valgus and both elbows held in fixed flexion. His fingers had varying degrees of fixed flexion. The lower limbs were unaffected. Laboratory evaluation within normal ranges. extensive dystrophic soft tissue calcification around both elbows outlining the joint capsules. dystrophic soft tissue calcification in the bilateral axillae extensive “sheet like” soft tissue dystrophic calcifications overlying the posterior elements of the vertebral column separate from the vertebrae. Histology showed muscle replacement by hyaline cartilage and bone with intervening fibromyxoid stroma. Discussion & Conclusions This case is meant to raise awareness of this rare disease across Africa. The misdiagnosis of FOP approaches 90% of cases worldwide. Definitive genetic testing of FOP is now available and can now confirm a diagnosis before the appearance of heterotopic ossifications. Clinical suspicion of FOP early in life on the basis of malformed great toes can lead to early clinical diagnosis. Current management focuses on early diagnosis, avoidance of trauma and optimization of function. A short course of oral steroids is beneficial in prevention of flares.

Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives.

Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions remain unanswered, such as the relationships between diet, hyperuricemia and gout flares or the mechanisms by which urate induces inflammation. Recent advances have identified gene variants associated with gout incidence. Nevertheless, genetic origins of gout combined to diet-related possible uric acid overproduction account for the symptoms in only a minor portion of patients. Hence, additional factors must be at play. Here, we review the impact of epigenetic mechanisms in which nutrients (such as ω-3 polyunsaturated fatty acids) and/or dietary-derived metabolites (like urate) trigger anti/pro-inflammatory responses that may participate in gout pathogenesis and severity. We propose that simple dietary regimens may be beneficial to complement therapeutic management or contribute to the prevention of flares in gout patients.

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

BackgroundImmune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients. MethodsInstitutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab. ResultsTwenty-two patients were identified. Two were treated prophylactically. Twenty were treated for management of irAEs. Median time to irAE onset from ICI start was 48 days (range 8–786) and from irAE onset to tocilizumab 32 days (range 1–192). Median time to irAE resolution from tocilizumab was 6.5 days (range 1–93). Clinical improvement/benefit was demonstrated in 21/22 patients. Median CRP prior to ICI administration was 32 mg/l (range 0.3–99), at the onset of irAE 49.5 mg/L (range 0.3–251, P = 0.047) and after tocilizumab 18 mg/L (range 0.3–18, P = 0.0011). Tocilizumab was well tolerated with self-limiting and transient toxicities in 11 (50%) patients. From start of ICI, median progression-free survival was 6 months (range 3.9–18.8) and median overall survival was not reached. ConclusionsTocilizumab was a well-tolerated and effective steroid-sparing treatment for both management of irAEs, as well as prevention of flare of pre-existing auto-immune disorders. Prospective trials to evaluate its efficacy and impact on cancer outcomes compared with standard strategies are required.