Remission In Arthritis Research Articles

Juvenile idiopathic arthritis management: insights into the utilization of intra-articular corticosteroid injections

ABSTRACT Background Juvenile idiopathic arthritis (JIA) is a common chronic rheumatic disease in children, requiring careful management to reduce both short- and long-term morbidity. In this study, our objective was to assess the clinical features of patients diagnosed with JIA who received intra-articular corticosteroid injections (IACI). Methods In this retrospective study, we evaluated the clinical and laboratory characteristics of 225 JIA patients monitored from January 2012 to October 2023 at a tertiary care center. We focused on patients who underwent intra-articular corticosteroid injections (IACI) as part of their treatment. Triamcinolone hexacetonide (TH) was used due to its demonstrated safety and efficacy. Results Our analysis revealed that IACI, particularly utilizing TH, was a widely employed and effective adjunct therapy, contributing to rapid symptom relief and local disease control. Patients receiving IACI exhibited earlier symptom onset, younger age at diagnosis, longer follow-up durations, and higher cumulative treatment burden (p < 0.001, p < 0.001, p < 0.01, p < 0.001 respectively). Despite inconclusive acute-phase reactants, a higher frequency of ANA positivity and elevated initial lymphocyte counts were associated with increased IACI use (p < 0.001, p < 0.001 respectively). Importantly, on a joint basis, a high percentage of arthritis remission following IACI underscores its efficacy and favorable safety profile. Conclusions Notably, the high percentage of arthritis remission achieved with intra-articular corticosteroid injections (IACI) on a joint-specific basis highlights its efficacy and favorable safety profile. A lymphocyte count exceeding 5000/mm3 at the time of diagnosis may serve as an early indicator for considering intra-articular steroid administration. These findings emphasize the need for nuanced and individualized treatment strategies in JIA management to optimize outcomes for affected children.

Clinical and Ultrasonographic Remission in Bio-naïve and Bio-failure Patients with Rheumatoid Arthritis at 24Weeks of Upadacitinib Treatment: The UPARAREMUS Real-Life Study.

Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week24. The proportion of patients achieving clinical remission with different composite indexes at week12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. After 12weeks and 24weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24weeks,63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Potential difficult-to-treat psoriatic arthritis real-world prevalence and contributing factors.

The challenge of achieving low disease activity or remission in psoriatic arthritis (PsA) is an unmet need for many patients. Persistent disease activity in PsA may require treatment adjustments due to its complex pathogenesis and varied tissue involvement, highlighting the need for dedicated definitions. This study evaluates patients' frequency and contributing factors with potential "difficult-to-treat PsA (D2TPsA)", similar to the EULAR definition of D2T rheumatoid arthritis. A retrospective study was conducted at two tertiary centres to define potential D2TPsA, defined as failure of ≥1 conventional synthetic disease-modifying anti-rheumatic drug (DMARD) and ≥2 biological or targeted synthetic DMARDs with different mechanisms of action. Of the 171 patients included in the study, 116 (67.8%) were women; the average age was 48.16 ±11.23 years. D2TPsA was detected in 33 patients (19.3%). This group exhibited a longer disease duration, higher disease burden (median number of tender and swollen joints, patient and physician global evaluation, morning stiffness, erythrocyte sedimentation rate and C-reactive protein, DAPSA), HLA-B27 positivity, and higher prevalence of peripheral involvement. Secukinumab usage and mean glucocorticosteroid dosage were significantly higher in the D2TPsA group. Comorbidities such as fibromyalgia (FM) and diabetes mellitus (DM) and the median number of comorbidities were significantly higher in D2TPsA. In multivariate analysis, FM, DM, and HLA-B27 positivity were independently associated with D2TPsA. This study underscores the impact of comorbidities on PsA disease activity and emphasises the need for further research to differentiate treatment challenges influenced by comorbidities from true treatment resistance.

“It means almost forgetting that you've got a disease”: An OMERACT study to define independence in the context of rheumatoid arthritis remission from the patient perspective

AimsOur previous work identified pain, fatigue, and independence as missing from the ACR/EULAR rheumatoid arthritis (RA) remission criteria from the patient perspective. Validated measures exist for pain and fatigue, but not for independence. As a first step towards developing such a measure, this study aimed to understand ‘Independence’ in the context of RA remission from the patient perspective. MethodsInternational qualitative research study comprising five focus groups of 19 participants with RA. Data were analysed using reflexive thematic analysis. ResultsFive overarching themes were identified, underpinned by a construct of “stages of independence”. Independence means at least being ‘physically and functionally able’ but may go beyond this and enable ‘participation beyond function’, ‘cognitive independence’, and ‘having or taking control’. There was no agreement on whether assistance is an aid to independence or undermines ability to achieve independence (‘assistance is complicated’). The construct “Stages of independence” acknowledges that Independence may mean different things to different patients and there may be other factors beyond disease activity that hold patients in each of these stages. ConclusionThese novel data suggest a desirable definition of independence includes full active participation without the need to consider or work around disease activity, and cognitive independence from thoughts of RA. Independence in RA remission is a complex concept and next steps will be to seek patient and professional agreement on the most important issues raised in these focus groups to take forward to developing a measure for independence in the context of RA remission from the patient perspective.

Differences and Similarities in the Feet of Metatarsalgia Patients with and without Rheumatoid Arthritis in Remission.

Objectives: Metatarsalgia continues to be a problem in patients with rheumatoid arthritis (RA) in remission (remRA), as well as in the non-rheumatic population, with a mechanical origin. Identify and compare clinical, morphological, disability, synovitis (ultrasound), and radiological osteoarticular damage characteristics in two groups of patients with lesser-ray metar-tarsalgia, with remRA, and without RA. Methods: Cross-sectional study with 84 patients with remRA (mRA) and 60 patients without RA (nmRA). The study evaluated five clinical variables (pain, Foot Function Index (FFI), joint mobility, digital deformities, and foot type), a radiological variable (osteoarticular damage), and an ultrasound variable (metatarsal synovitis). The data were analysed using descriptive and correlational techniques. Results: There were no significant differences in sex, age, body mass index (BMI), or degree of pain. Both groups showed a high prevalence of limited joint mobility for the ankle and first metatarsal phalanx (DF1st MTPJ) and digital deformities, with no statistically significant differences. Similarly, there were no differences in lesser-ray synovitis. On the other hand, there were differences in mRA with greater disability and activity limitation (FFI), LDD (lesser-ray digital deformities) stiffness, first-ray deformities, radiological damage, synovitis in 1st MTPJ, and positive Doppler (five patients). Conclusions: Metatarsalgia presents similarities in both populations. Biomechanical factors may influence the symptoms and presence of synovitis in patients with RA in remission. Other characteristics are more frequent in mRA, which could be related to the disease; thus, future research should include both biomechanical and ultrasound exploration of the foot in the valuation of patients in remission.

E067 Bimekizumab maintained efficacy responses through 52 weeks in biologic disease-modifying antirheumatic drugnaïve patients with psoriatic arthritis who were responders at week 16: results from BE OPTIMAL, a phase 3, activereference study

E067 Bimekizumab maintained efficacy responses through 52 weeks in biologic disease-modifying antirheumatic drugnaïve patients with psoriatic arthritis who were responders at week 16: results from BE OPTIMAL, a phase 3, activereference study

Drug effectiveness of 2nd and 3rd TNF inhibitors in psoriatic arthritis – relationship with the reason for withdrawal from the previous treatment

ObjectiveTo investigate real-world retention and remission rates in PsA patients initiating a 2nd or 3rd TNFi and the association with reason for discontinuation from the previous TNFi-treatment. MethodsProspectively collected routine care data from 12 European registries were pooled. Retention rates (Kaplan-Meier estimation) and crude/LUNDEX-adjusted rates of Disease Activity Score 28 and Disease Activity index for PSoriatic Arthritis (DAS28 and DAPSA28) remission were calculated and compared with adjusted Cox regression analyses and Chi-squared test, respectively). ResultsWe included 5233 (2nd TNFi) and 1906 (3rd TNFi) patients. Twelve-month retention rates for the 2nd and 3rd TNFi were 68% (95%CI: 67–70%) and 66% (64–68%), respectively. Patients who stopped the previous TNFi due to AE/LOE had 12-month retention rates of 66%/65% (2nd TNFi), and 65%/63% (3rd TNFi), respectively. Patients who stopped the previous TNFi due to LOE after less vs more than 24 weeks had 12-month retention rates of 54%/69% (2nd TNFi), and 58%/65% (3rd TNFi). Six-month crude/LUNDEX-adjusted DAS28 remission rates were 48%/35% and 38%/27%, and DAPSA28 remission rates were 19%/14% and 14%/10%, for the 2nd and 3rd TNFi. ConclusionTwo-thirds of patients remained on TNFi at 12months for both the 2nd and 3rd TNFi, while one-third and one-quarter of patients were in DAS28 remission after 6months on the 2nd and 3rd TNFi. While drug effectiveness was similar in patients who stopped the previous TNFi due to AE compared to overall LOE, drug effectiveness was better in patients who had stopped the previous TNF due to secondary LOE compared to primary LOE.

Deconvolution of synovial myeloid cell subsets across pathotypes and role of COL3A1+ macrophages in rheumatoid arthritis remission.

Monocyte/macrophage (Mo/Mp) is a critical cell population involved in immune modulation of rheumatoid synovitis (RA) across different pathotypes. This study aims to investigate the contribution of Mo/Mp clusters to RA activity, and the biological function of particular subtypes in RA remission. We integrated single-cell RNA sequencing datasets from 4 published and 1 in-house studies using Liger selected by comparison. We estimated the abundance of Mo/Mp subtypes in bulk RNA-seq data from the 81 patients of the Pathobiology of Early Arthritis Cohort (PEAC) using deconvolution analysis. Correlations between Mo/Mp subtypes and RA clinical metrics were assessed. A particular cell type was identified using multicolor immunofluorescence and flow cytometry in vivo and successfully induced from a cell line in vitro. Potential immune modulation function of it was performed using immunohistochemical staining, adhesion assay, and RT-qPCR. We identified 8 Mo/Mp clusters. As a particular subtype among them, COL3A1+ Mp (CD68+, COL3A1+, ACTA2-) enriched in myeloid pathotype and negatively correlated with RA severity metrics in all pathotypes. Flow cytometry and multicolor immunofluorescence evidenced the enrichment and M2-like phenotype of COL3A1+ Mp in the myeloid pathotype. Further assays suggested that COL3A1+ Mp potentially attenuates RA severity via expressing anti-inflammatory cytokines, enhancing Mp adhesion, and forming a physical barrier at the synovial lining. This study reported unexplored associations between different pathologies and myeloid cell subtypes. We also identified a fibroblast-and-M2-like cluster named COL3A1+ Mp, which potentially contributes to synovial immune homeostasis. Targeting the development of COL3A1+ Mp may hold promise for inducing RA remission.

Biomarker combination predicting imminent relapse after discontinuation of biological drugs in patients with rheumatoid arthritis in remission.

Compared to conventional disease-modifying antirheumatic drugs (DMARDs), biological DMARDs demonstrate superior efficacy but come with higher costs and increased infection risks. The ability to stop and resume biological DMARD treatment while maintaining remission would significantly alleviate these barriers and anxieties. The objective of this study was to identify biomarkers that can predict an imminent relapse, hopefully enabling the timely resumption of biological DMARDs before relapse occurs. Forty patients with rheumatoid arthritis who had been in remission for more than 12 months were included in the study. The patients discontinued their biological DMARD treatment and were monitored monthly for the next 24 months. Out of the 40 patients, 14 (35%) remained in remission at the end of the 24-month period, while 26 (65%) experienced relapses at different time points. Among the relapse cases, 13 patients experienced early relapse within 6 months, and another 13 patients had late relapse between 6 months and 24 months. Seventy-three cytokines in the sera collected longitudinally from the 13 patients with late relapse were measured by multiplex immunoassay. Using cytokines at two time points, immediately after withdrawal and just before relapse, volcano plot and area under the receiver operating characteristic curves (AUC) were drawn to select cytokines that distinguished imminent relapse. Univariate and multivariate logistic regression analyses were used for the imminent relapse prediction model. IL-6, IL-29, MMP-3, and thymic stromal lymphopoietin (TSLP) were selected as potential biomarkers for imminent relapse prediction. All four cytokines were upregulated at imminent relapse time point. Univariate and multivariate logistic regression showed that a combination model with IL-6, MMP-3, and TSLP yielded an AUC of 0.828 as top predictors of imminent relapse. This methodology allows for the prediction of imminent relapse while patients are in remission, potentially enabling the implementation of on- and off-treatments while maintaining remission. It also helps alleviate patient anxiety regarding the high cost and infection risks associated with biological DMARDs, which are the main obstacles to benefiting from their superb efficacy.

Latest Treatment Perspectives for IBD-related Arthritis - a review

Introduction: IBD-related arthritis (spondyloarthropathy) is the most common extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD) and is often considered a formidable clinical challenge. Emergence of TNFα-antagonists has revolutionised the clinical approach to management of IBD-related arthritis and remains the mainstay of the therapy. However, its use presents several limitations, underscoring the need for new treatment modalities. Recently, new agents have been approved for the management of IBD, although their influence on IBD-related arthritis has been scarcely investigated. Aim of the Study: The aim of the study was to collect and analyse current literature regarding the efficacy of new agents used for treating IBD-related arthritis. Methods and Materials: Extensive research was conducted using the PubMed, ScienceDirect database and Google Scholar, with the primary focus on literature from the past 5 years. Firstly, potential novel treatment options for IBD-related arthritis were obtained. The names of the drugs were juxtaposed with terms related to “IBD-related arthritis” to gather data regarding their efficacy in said condition. Additionally, references from selected articles were included in the analysis. Results: Emerging treatment options show promising results in achieving remission of IBD-related arthritis. However, our study revealed research gap as the current literature lacks large-scale, prospective studies that assess the efficacy of the aforementioned agents in achieving a resolution of IBD-related arthritis. Therefore, the results of our study encourage further research, with special emphasis on large-scale randomised controlled trials.

Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission.

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare - CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells - further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention.

Window of opportunity in psoriatic arthritis: the earlier the better?

ObjectivesTo investigate whether there is a window of opportunity for psoriatic arthritis (PsA) patients and to assess which patient characteristics are associated with a longer diagnostic delay.MethodsAll newly diagnosed, disease-modifying...

PSORIATIC ARTHRITIS: PROBLEMS AND SOLUTIONS (CASE REPORT)

The purpose of this study is to evaluate the effectiveness of therapy for psoriatic arthritis with tumor necrosis factor inhibitor α–Adalimumab. Material and methods. Retrospective and prospective analyses of psoriatic arthritis course were performed in a patient along with a comprehensive examination before and after administering therapy with a tumor necrosis factor inhibitor α-Adalimumab. The diagnosis of the patient was made on the basis of psoriatic arthritis classification criteria, the assessment of psoriatic rashes was performed according to PASI index. The laboratory study included complete blood cell count and biochemical blood tests. The patient underwent X-ray examinations of the joints and magnetic resonance imaging of the lumbosacral spine in the STIR mode. Study results. The patient's first manifestations of psoriasis were detected at the age of 12 years. At the age of 22, the patient had pain in the lower back of VAS 2-3 points, as well as enthesites in the area of the lateral epicondyle of humerus, wings of the iliac bones, trochanter major, the upper edge of the patella and tibial tuberosity, the PASI index was 17.3 points. In order to relieve pain, the patient took non-steroidal anti-inflammatory drugs. Against the background of therapy with non-steroidal anti-inflammatory drugs, the intensity of pain in the lower back decreased, but enthesites persisted. At the age of 35, the patient was diagnosed with psoriatic arthritis, activity III, stage II, dactylitis, enthesites, PASI index 38.5 points; right-sided active sacroiliitis, ASDAS ESR index activity was 3.92 points, joint functional insufficiency of the 2nd degree. Methotrexate therapy was prescribed. There was no positive dynamics against the background of treatment, in connection with this, therapy with genetically engineered biological drugs was initiated. We observed positive dynamics in the clinical course of psoriatic arthritis when Adalimumab was included in the treatment: after the 2nd week of treatment, the articular syndrome subsided, joint pain decreased when evaluated on a scale of 2-3 points, the number of psoriatic plaques on the trunk and limbs decreased as well, the index of psoriatic rashes was 5.3 points. After 8 weeks from the start of therapy with Adalimumab, regression of pathological skin rashes was noted, the index of psoriatic rashes was 0 points. Conclusions. Therapy with Adalimumab in the patient resulted in regression of psoriatic manifestations on the skin, suppression of psoriatic arthritis activity. The study showed the clinical effectiveness of a genetically engineered biological drug – Adalimumab in achieving persistent clinical remission of psoriatic arthritis.

Assessment of quality of life and physical activity in patients with oligoarticular juvenile idiopathic arthritis in remission.

The purpose of this study was to evaluate physical activity (PA) and health-related quality of life (HRQOL) in children with oligoarticular juvenile idiopathic arthritis (JIA) in remission in comparison with healthy peers and to determine the disease-related factors affecting PA levels. This study was conducted with 50 oligoarticular JIA patients in remission and 50 healthy peers between 9 and 14years. Demographic and clinical characteristics, laboratory parameters, and treatments were noted from electronic medical records. HRQOL was assessed with the Pediatric Quality of Life Inventory (PedsQL). PA was evaluated with the Physical Activity Questionnaire for Children (PAQ-C). Oligoarticular JIA patients had significantly lower self-reported median PedsQL scores in the domains of school functioning and social functioning compared to the control group (67.5 (10) vs. 75 (25), p = 0.001 and 70 (15) vs. 85 (26.3), p < 0.001, respectively). The median PAQ-C score was 2.6 (1.1) in patients with JIA and 3 (0.9) in their healthy peers (p = 0.02). The PAQ-C score was 2.8 (1.2) in patients < 8years at the disease onset and 2.3 (1) in those aged ≥ 8years (p = 0.022). There was no significant difference in the number of affected joints, type of affected joint, MTX and biologic agent treatment, and remission with or without drugs with the total score of the PedsQL and PAQ-C. All PedsQL domains were positively correlated with the PAQ-C. Conclusion: Oligoarticular JIA patients demonstrated lower PA and HRQOL scores compared to healthy controls despite favorable disease control. What is Known: • Oligoarticular JIA has fewer functional limitations and disabilities compared to other JIA subtypes. • As JIA can affect all aspects of a child's life, there is a need to improve the quality of life related to the disease. What is New: • It should be considered that patients with oligoarticular JIA may show lower PA and HRQOL scores compared to healthy controls despite favorable disease control. • Since there may be a relationship between PA and HRQOL, factors that may affect PA should be investigated to provide a holistic approach to JIA treatment.

Efficacy and safety of baricitinib in treatment of systemic lupus erythematosus: a systematic review and meta-analysis

BackgroundSLE is an autoimmune disease marked by broad immunological dysregulation and multi-system inflammation. Baricitinib is one of the novel treatments for SLE. We conducted this meta-analysis to evaluate its safety and effectiveness in treating SLE.MethodWe looked for all published randomized controlled trials in PubMed, Scopus, Web of Science, and Cochrane and included all RCTs comparing baricitinib and placebo in the treatment of SLE. Review Manager 5.4 program was used for data analysis.ResultsThree trials with a total of 1849 individuals were included. Participants in the baricitinib group were significantly more likely to attain SRI-4 response than those in the placebo group [RR = 1.11, 95% CI (1.02, 1.21), P = 0.01]. Additionally, baricitinib performed better than the placebo in terms of reduction of ≥ 4 points from baseline in SLEDAI-2 K score [RR = 1.13, 95% CI (1.04, 1.22), P = 0.004]. In terms of SLEDAI-2 K remission of arthritis or rash, baricitinib was also superior to placebo [RR = 1.08, 95% CI (1.00, 1.17), P = 0.04]. Treatment-emergent adverse events did not differ significantly [RR = 1.01, 95% CI (0.97, 1.05), P = 0.61].ConclusionBaricitinib is potentially safe and effective in the treatment of SLE. It has successfully met the study’s primary endpoint and some secondary endpoints highlighting its potential to improve the outcomes of SLE. Despite achieving an SRI-4 response, glucocorticoids sparing and some other secondary outcomes weren’t reached by baricitinib.

Molecular profiling of clinical remission in psoriatic arthritis reveals dysregulation of FOS and CCDC50 genes: a gene expression study.

In psoriatic arthritis (PsA), the primary goal of treatment is clinical remission. This study aimed to characterize the molecular profile underlying the induced clinical remission in patients with PsA, comparing the remission state and the healthy condition. Whole blood transcriptomic analysis was performed on groups of 14 PsA patients in TNFi-induced clinical remission (DAPSA ≤ 4), 14 PsA patients with active disease (DAPSA > 14), and 14 healthy controls (HCs). Then, all differentially expressed genes (DEGs) derived from remission vs. HC comparison were analyzed for functional and biological characteristics by bioinformatics software. The gene expression of 12 genes was then validated by RT-qPCR in an extended cohort of 39 patients in clinical remission, 40 with active disease, and 40 HCs. The transcriptomic analysis of PsA remission vs. HCs highlighted the presence of 125 DEGs, and out of these genes, 24 were coding genes and showed a great involvement in immune system processes and a functional network with significant interactions. The RT-qPCR validation confirming the down- and upregulation of FOS (FC -2.0; p 0.005) and CCDC50 (FC +1.5; p 0.005) genes, respectively, in line with their role in orchestrating inflammation and bone metabolism processes, may be related to PsA pathophysiology. The transcriptomic profile of clinical remission in PsA is similar to a healthy condition, but not identical, differing for the expression of FOS and CCDC50 genes, which appears to play a key role in its achievement.

Treatment of active systemic lupus erythematosus with baricitinib: A meta-analysis of randomized controlled trials.

This study aimed to evaluate the safety and effectiveness of baricitinib in patients with systemic lupus erythematosus (SLE). We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to find relevant publications. Using data from randomized controlled trials (RCTs), we performed a meta-analysis to investigate the safety and efficacy of baricitinib in patients with active SLE who did not respond well to standard treatments. A total of 1849 individuals (1235 experimental participants and 614 controls) from three RCTs on baricitinib were included. A reduction of ≥ 4 points from baseline in SLEDAI-2K score in the baricitinib 4mg group was greater than the placebo group's reduction (odds ratio [OR] = 1.407, 95% confidence interval [CI] 1.123-1.763, p = .003). The baricitinib 4mg group significantly outperformed the placebo group in terms of SLEDAI-2K remission of arthritis or rash (OR = 1.327, 95% CI = 1.059-1.663, p = .014). Other effectiveness outcomes such as the SRI4 response did not substantially improve in the baricitinib 4mg group when compared with the placebo group. And there were no significant increase in the efficacy outcomes in the baricitinib 2mg group than in the placebo group. However, there was a substantially higher incidence of severe adverse events (SAE) and serious infections in the baricitinib 4mg group (OR = 1.493, 95% CI = 1.002-2.225, p = .049; OR = 2.303, 95% CI = 1.147-4.622, p = .019) compared to the placebo group. There were no differences between the baricitinib 2mg and placebo groups in any of the safety outcome data. Meta-analysis reveals that baricitinib 4mg is beneficial for treating active SLE in terms of a reduction of ≥ 4 points from baseline in SLEDAI-2K score and SLEDAI-2K remission of arthritis or rash. However, the higher frequency of SAEs and serious infections was observed in the group receiving baricitinib 4mg.

OA21 Are novel anti-IL5 biologics triggering rheumatoid arthritis?

Abstract Introduction Biologics are being increasingly used for the treatment of inflammatory diseases across a wide range of specialties. Of particular interest, it is well established that monoclonal therapy for one inflammatory disease may paradoxically trigger another inflammatory disease, for example TNF therapy triggering multiple sclerosis, and IL-17 therapy for psoriasis linked to inflammatory bowel disease. Here we report the case of a patient who developed anti-CCP positive rheumatoid arthritis soon after starting a novel anti-IL-5 biologic used to treat his severe eosinophilic asthma. Case description This 77-year-old gentleman with a background of severe eosinophilic asthma presented to our early arthritis clinic 18 months after having been started on either mepolizumab or a long-acting IL-5 blocker as part of a clinical trial. Prior to starting biologics, his asthma had been poorly controlled with salbutamol, Fostair, tiotropium inhalers and low-dose corticosteroids. Within weeks, he developed symmetrical arthralgias involving small joints, particularly his wrists and knuckles, as well as significant early morning stiffness lasting more than one hour. On examination, he had clinical synovitis in the wrists and metacarpophalangeal joints bilaterally, as well as right shoulder capsulitis with limiting range of motion. Blood tests revealed a raised CRP of 24mg/L, WCC 8.77 10*9/L, rheumatoid factor of 263.2 iu/mL and anti-CCP antibody of &amp;gt; 300 U/mL. Ultrasound imaging of the hands and wrists bilaterally showed grade II grey scale with grade II power Doppler, and some erosions in the wrists bilaterally. There was hypoechogenicity of the left extensor carpi ulnaris tendon with some associated grey scale and power Doppler. He was diagnosed with rheumatoid arthritis as per the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) diagnostic criteria and started on prednisolone 10mg daily as a rescue therapy to reduce the inflammation, followed by sulfasalazine one month later as the disease modifying agent. He was followed-up in rheumatology clinic two months later and showed significant improvements: the pains and swellings of his joints had settled, and whilst he still gets early morning stiffness this is not so debilitating. His inflammatory markers had also resolved with CRP &amp;lt;5.0mg/L and WCC 9.31 10*9/L. Discussion We report a case of new onset rheumatoid arthritis associated with the commencement of an anti-IL-5 biologics for severe asthma. To our knowledge, this has only been reported in the literature on a handful of occasions and in each case the patients were on oral corticosteroids with the majority being weaned off in parallel to developing the new symptoms [1,2]. As such there has been a challenge in associating the development of arthritis with the initiation of the anti-IL-5 biologic, as opposed to the withdrawal of steroids unmasking a pre-existing disease. Emerging evidence has implicated a core role for regulatory eosinophils (rEos) in the resolution of rheumatoid arthritis (RA) [3]. In murine models of RA, an expansion of rEos in the synovium was sufficient to bring about remission of arthritis. Inhibiting the IL-5 pathway would subsequently induce relapse of the arthritis [3]. Further studies are required to characterise the significance of these findings in clinical cohorts and to identify whether there is an actual association between novel anti-IL-5 biologics and rheumatoid arthritis. Key learning points Our improved understanding of the mechanisms underlying inflammatory diseases has led to the increased use of biological therapies in treating these conditions. However, these therapies may be paradoxically triggering other inflammatory diseases, particularly autoimmune rheumatological diseases. Here we have identified a patient who developed anti-CCP positive rheumatoid arthritis soon after commencing a novel anti-IL5 for severe asthma. Mechanistically, this may be related to the depletion of regulatory eosinophils tipping the balance towards pro-inflammatory pathways in the synovial joints. More work is required to identify whether this phenomenon is being more widely observed in clinical practice, and if so how we can best manage it going forwards.

Neutrophil autophagy induced by monosodium urate crystals facilitates neutrophil extracellular traps formation and inflammation remission in gouty arthritis.

Neutrophil extracellular traps (NETs) are composed of chromatin filaments coated with granular and cytosolic proteins, which contribute to the pathogenesis and progression of immune-related diseases. NETs are frequently observed in gouty arthritis, but the related mechanisms remain poorly understood. The aim of our study was to systematically elucidate the molecular mechanisms of self-remitting effects in gouty arthritis, and the causative relationship between neutrophil autophagy and NETs. The air pouch and paw edema model were used to simulate gouty arthritis in mice. Neutrophil infiltration and the formation of NETs were found in gouty arthritis. Interestingly, monosodium urate (MSU) crystals could induce the formation of NETs, degrade inflammatory factors, and alleviate the inflammatory response in gouty arthritis. In addition, MSU crystals resulted in profound molecular alterations in neutrophils using RNA-seq analysis, including autophagy activation. MSU crystals could activate neutrophil autophagy in vitro, and autophagy activators and inhibitors could regulate the formation of NETs. Furthermore, we explored the mechanism of autophagy-induced NETs. Autophagy related protein 7 (ATG7) produced by neutrophils stimulated with MSU crystals worked synergistically with p53 to enter the nucleus, promoting peptidyl arginine deiminase 4 (PAD4) expression, and inducing the formation of NETs. Finally, we substantiated that neutrophil autophagy regulates the severity of gouty arthritis via the formation of NETs in PAD4 -/- mice. Our results indicated that the autophagy of neutrophils regulates the formation of NETs and degrades inflammatory factors. Regulating autophagy and interfering with the formation of NETs represents a potential therapeutic approach against gouty arthritis during clinical practice.

Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study

ObjectivesWe aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA).MethodsWe used data from the ReFlaP, an international multi-centre cohort...