Higher Disease Activity Scores Research Articles

P138 Inequity in Clinical Commissioning Group funding across England for high-cost biologic drugs in rheumatoid arthritis

Abstract Background/Aims Biologic, and targeted, disease-modifying antirheumatic drugs (bDMARDs/tDMARDs) are recommended for patients in England with high disease activity score rheumatoid arthritis (HDAS-RA) who do not respond to two or more conventional synthetic DMARDs. To prescribe bDMARDs/tDMARDs in England, prescribers must apply for funding via their local clinical commissioning group (CCG). The project aim was to review whether CCGs across England had defined high cost drugs pathways for bDMARDs/tDMARDs use in HDAS-RA and if so, what this pathway looked like regarding drug choice, order of availability, and ability to prescribe as monotherapy. Methods We submitted a freedom of information (FOI) request in October 2021 to all CCGs within England to obtain their high cost drug pathway for bDMARDs/tDMARDs use in HDAS-RA. We then manually reviewed the pathways to determine whether the CCG specified an order of drug prescribing. Data was also gathered on whether CCGs allowed abatacept (ABT), rituximab (RTX), and golimumab (GOL) to be prescribed as monotherapy. Results All 107 CCGs in England responded to the FOI request. 69 out of 107 CCGs (65%) had a pathway for bDMARDs/tDMARDs prescribing. 60 out of 69 CCGs (87%) specified an order for drug prescribing in RA. Within their pathways, CCGs generally fell into 3 prescribing preferences. Table 1 summarises these pathway recommendations. 39 (57%), 59 (86%), and 6 (9%) CCGs allowed ABT/RTX/GOL to be prescribed as monotherapy respectively. RTX monotherapy was specifically allowed outside of special indications such as cancer, interstitial lung disease and multiple sclerosis. Conclusion These findings show there is significant variation across England regarding which bDMARDs/tDMARDs patients can receive for HDAS-RA resulting in a postcode lottery. Several studies support the use of ABT/RTX/GOL as monotherapy and registry data shows that 30-40% of RA patients are administered ABT/RTX/GOL as monotherapy for methotrexate intolerance/contraindication. Lack of NICE appraisal, however, means some CCGs mandate individual funding requests for monotherapy prescribing. We would like to use these results to help negotiate equitable access to bDMARDs/tDMARDs nationwide. Disclosure O. Buckeldee: None. R. Khanna: None. L. Snell: None. L. Attipoe: None.

Evaluation of the Role of Affective Temperamental Features, Automatic Thoughts, and Symptom Interpretation on Disease Activity in Patients with Axial Spondyloarthritis.

Axial spondyloarthritis is a systemic and chronic inflammatory disease. Psychological liability to depression and anxiety influences the disease process, prognosis, and treatment outcomes of other medical conditions. Early detection and treatment of these psychiatric conditions would also help in improving the physical functioning of patients with axial spondyloarthritis by reducing the patient's anxiety and depression symptoms. We evaluated the affective temperamental features, automatic thoughts, symptom interpretation, and their relationship with disease activity in patients with axial spondyloarthritis. A total of 152 patients diagnosed with axial spondyloarthritis are recruited. Axial spondyloarthritis disease activity was calculated by Bath Ankylosing Spondylitis Disease Activity Index. Depression and anxiety levels were screened with Hospital Anxiety and Depression Scale while affective temperament was evaluated with Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-autoquestionnaire version and automatic thoughts were screened with Symptom Interpretation Questionnaire, and Automatic thoughts questionnaire. It was observed that 48% (n = 73) were female. The mean age was 43.5 (10.5) years, Bath Ankylosing Spondylitis Disease Activity Index score was 3.97 (1.14). According to the Bath Ankylosing Spondylitis Disease Activity Index scale, 53.30% (n = 81) of the patients were in high disease activity. We found that HAD-depression, HAD-anxiety, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-autoquestionnaire version, Symptom Interpretation Questionnaire, and Automatic Thoughts Questionnaire scores were significantly higher in the high disease activity group. Patients' temperament characteristics and mood disorders may affect composite disease activity scores such as Bath Ankylosing Spondylitis Disease Activity Index. In patients with high disease activity scores despite receiving appropriate treatment, mood disorders may need to be evaluated. There is a need to develop disease activity scores unaffected by mood disorders.

Factors Leading to Diagnostic and Therapeutic Delay of Rheumatoid Arthritis and Their Impact on Disease Outcome.

Objective To identify the factors which leadto delay in diagnosis and initiation of disease-modifying anti-rheumatic drugs (DMARDs) inrheumatoid arthritis (RA) patients and their impact on disease outcome and functional ability. Methodology This cross-sectional study was conducted from June 2021 to May 2022 at the Department of Rheumatology and Immunology, Sheikh Zayed Hospital, Lahore. Inclusion criteria were patients aged >18 years who were diagnosed with RA, based on American College of Rheumatology (ACR) criteria 2010. Delay was defined as any sort of delay which leads to delay in diagnosis or initiation of treatment of more than three months. The factors and impact on disease outcome were measured by using Disease Activity Score-28 (DAS-28) for disease activity and Health Assessment Questionnaire-Disability Index (HAQ-DI) for functional disability. The collected data were analyzed with Statistical Package for Social Sciences (SPSS) version 24 (IBM Corp., Armonk, NY, USA). Results One hundred and twenty patients were included in the study. Mean delay in referral to a rheumatologist was 36.75±61.07 weeks. Fifty-eight (48.3%) patients with RA were misdiagnosed before presentation to a rheumatologist. Sixty-six(55%) patients had the perception that RA is a non-treatable disease. Delay in diagnosis of RA from onset of symptoms (lag 3) and delay in start of DMARDs fromonset of symptoms (lag 4) were significantly associated with increased DAS-28 and HAQ-DI scores (p-value 0.001). Conclusion The factors which led to diagnostic and therapeutic delay were delayed consultation with a rheumatologist, old age, low education status and low socioeconomic status. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies had no role in diagnostic and therapeutic delay. Many RA patients were misdiagnosed with gouty arthritis and undifferentiated arthritis before consulting a rheumatologist. This diagnostic and therapeutic delay compromises RA management leading to high DAS-28 and HAQ-DI in RA patients.

Dry eye disease and high disease activity score (DAS-28) in rheumatoid arthritis: An underrated combination.

To determine the association of dryness of eyes with rheumatoid arthritis severity. The cross-sectional, observational study was conducted at the Jinnah Medical College Hospital, Karachi, from December 2020 to May 2021, and comprised adult patients of either gender with rheumatoid arthritis who were diagnosed on the basis of clinical and serological investigations. Data was collected using a structured pre-tested questionnaire. Ocular Surface Disease Index questionnaires with Tear Film Breakup Time were used to assess the severity of dry eyes. Disease Activity Score-28 with erythrocyte sedimentation rate was used to assess the severity of rheumatoid arthritis. Association between the two was explored. Data was analysed using SPSS 22. Of the 61 patients, 52(85.2%) were females and 9(14.8%) were males. The overall mean age was 41.7±12.8 years, with 4(6.6%) aged <20 years, 26(42.6%) aged 21-40 years, 28(45.9%) aged 41-60 years and 3(4.9%) aged >60years. Further, 46(75.4%) subjects had sero-positive rheumatoid arthritis, 25(41%) had high severity, 30(49.2%) had severe Occular Surface Density Index score and 36(59%) had decreased Tear Film Breakup Time. Logistic Regression analysis showed there were 5.45 times higher odds of having severe disease among the people with Occular Surface Density Index score >33 (p=0.003). In patients with positive Tear Film Breakup Time, there were 6.25 higher odds of having increased disease activity score (p=0.001). Disease activity scores of rheumatoid arthritis were found to have strong association with dryness of eyes, high Ocular Surface Disease Index score and increased erythrocyte sedimentation rate.

Red blood cell distribution width at diagnosis as a predictor factor in chronic phase-chronic myeloid leukemia patients treated with first-generation tyrosine kinase inhibitors

BACKGROUND: Chronic myelogenous leukemia is a hematological disorder of stem cells resulting from uncontrolled and unregulated growth of myeloid cells in the bone marrow. Since the introduction of tyrosine kinase inhibitors (TKIs), therapy has dramatically improved survival in these patients. TKIs treatment targeting BCR-ABL significantly improves the prognosis of patients with chronic myelogenous leukemia. To date, the validity of scoring systems is insufficient for predicting prognosis, and there are few studies of scoring systems for predicting treatment response and clinical efficacy of TKIs. OBJECTIVES: The objective of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict treatment response in chronic myeloid leukemia-chronic phase (CP) patients treated with first-generation TKI. PATIENTS AND METHODS: A prospective and retroprospective cohort study was conducted on chronic myeloid leukemia-CP patients treated with first-generation TKI at Iraqi Hematological Centers. The collection period was from December 2020 to November 2021. Patients were treated with first-generation TKIs as initial therapy and were followed up to assess the response by polymerase chain reaction (PCR). The assessment of RDW was done at baseline and then at 3, 6, 12, and 18 months after initiation of therapy. RESULTS: There were 150 patients included in this study. The mean age of patients was 43.7 ± 14 years (range: 18–84 years). Males were representing 48.6% and females 51.3%. The classification of baseline RDW showed that the majority of patients (53%) had high RDW. The RDW showed significant change over time, in which, it was significantly decreasing over time (P &lt; 0.05). Association between PCR over time and baseline RDW category showed that the high baseline RDW was associated with higher mean PCR at 3, 6, 12, and 18 months (P &lt; 0.05). The correlation between RDW at baseline and PCR at 3, 6, 12, and 18 months showed that there was a significant positive weak correlation between baseline RDW and PCR at 6, 12, and 18 months. The association between baseline RDW and the response showed that high baseline RDW was associated with higher failure rate at 6 and 12 months (P &lt; 0.05). CONCLUSION: RDW could be used in the prediction of response to treatment. Furthermore, high RDW showed significant association with high disease activity score, high white blood cell count, and lower hemoglobin, in addition to association and correlation with PCR level.

Assessment of Epstein-Barr virus, Candida albicans, and some periodontal pathogens in rheumatoid arthritis patients with periodontitis.

To comparatively investigate the periodontal results and microbial load in subgingival biofilm samples (SBS) in rheumatoid arthritis subjects and healthy volunteers. One hundred twenty subjects were classified into different cohorts: healthy (H-C); periodontitis with good systemic health (H-P); rheumatoid arthritis (RA) and good periodontal health (RA-C); and periodontitis with RA (RA-P). The periodontal parameters were recorded, and SBS were collected to determine periodontal pathogens including Epstein-Barr Virus (EBV) and Candida albicans using reverse transcription-polymerase chain reaction (RT-PCR). Subjects that had greater disease course, determined by moderate or high disease activity scores 28 (DAS28), suffered from worse oral health conditions (higher plaque index, gingival index, bleeding on probing, probing depth, and excessive clinical attachment loss) than those with low DAS28 scores. A higher prevalence of Treponema denticola (T. denticola) was observed in the RA-P group. Cyclic citrullinated peptide was associated with the occurrence of T. denticola and Campylobacter rectus. DAS28 using C-reactive protein (DAS28-CRP) had a significant association with Capnocytophaga gingivalis and EBV. The duration of the RA disease was associated with the presence of T. denticola. Subgingival microbial difference could reliably discriminate RA from healthy individuals. Especially, T. denticola and EBV may play a key role in periodontitis associated with RA.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p= .006), being male (p= .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p= 0.008) and high (DAS28 > 5.1) (p= 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p> 0.05). This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

Impact of disease burden or inflammation on nutritional assessment by the GLIM criteria in female patients with rheumatoid arthritis.

In 2018, the Global Leadership Initiative on Malnutrition (GLIM) released a global standard for evaluating malnutrition. The etiologies of malnutrition in the GLIM criteria includes disease burden/inflammation, but how this view affects nutritional assessment remains unclear. This study aimed to investigate the impact of disease burden/inflammation on the proportion of malnourished patients defined by GLIM criteria, and how differences in methods for determining disease burden/inflammation in GLIM criteria affect existing nutritional indices among patients with rheumatoid arthritis (RA). We also investigated factors associated with malnutrition in RA patients. Data from 135 female RA patients (66.8±12.6 years) were cross-sectionally analyzed. Among the etiologies of malnutrition, disease burden/inflammation was defined as: (1) moderate or higher disease activity score (disease activity score composite of the 28-joint score and erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2) [DAS-malnutrition (MN)]; (2) elevated C-reactive protein (CRP) ≥0.5mg/dL (CRP-MN); and (3) presence of RA (RA-MN). In each of the three conditions, nutritional indicators between well-nourished and malnourished groups were compared by analysis of covariance. Factors associated with malnutrition were analyzed with logistic regression analysis. The frequencies of malnutrition as defined by DAS-MN, CRP-MN, and RA-MN were 39%, 30%, and 71%, respectively. When malnutrition was defined by the DAS-MN and/or the CRP-MN, grip strength and serum ceruloplasmin, iron, and zinc levels showed significant differences between the well-nourished and malnourished groups (p<0.05). The use of targeted synthetic or biological disease-modifying antirheumatic drugs (ts-/b-DMARD) (OR=0.29; 95% CI 0.11-0.82), grip strength (OR=0.83; 95% CI 0.75-0.91), subjective reduction in walking speed (OR=5.24; 1.85-14.86) were significantly associated with malnutrition as determined by DAS-MN. Differences in disease burden/inflammation affect nutritional assessments. The number of malnourished patients with RA was negatively associated with the use of ts-/b-DMARDs and high physical function in women.

Disease trajectory of SLE clinical endpoints and covariates affecting disease severity and probability of response: Analysis of pooled patient-level placebo (Standard-of-Care) data to enable model-informed drug development.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Many investigational agents have failed or shown only modest effects when added to standard of care (SoC) therapy in placebo-controlled trials, and only two therapies have been approved for SLE in the last 60 years. Clinical trial outcomes have shown discordance in drug effects between clinical endpoints. Herein, we characterized longitudinal disease activity in the SLE population and the sources of variability by developing a latent disease trajectory model for SLE component endpoints (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI], Physician's Global Assessment [PGA], British Isles Lupus Assessment Group Index [BILAG]) and composite endpoints (Systemic Lupus Erythematosus Responder Index [SRI], BILAG-based Composite Lupus Assessment [BICLA], and Lupus Low Disease Activity State [LLDAS]) using patient-level historical SoC data from nine phase II and III studies. Across all endpoints, in predictions up to 52 weeks from the final disease trajectory model, the following baseline covariates were associated with a greater decrease in SLE disease activity and higher response to placebo + SoC: Hispanic ethnicity from Central/South America, absence of hypocomplementemia, recent SLE diagnosis, and high baseline disease activity score using SLEDAI and BILAG separately. No discernible differences were observed in the trajectory of response to placebo + SoC across different SoC medications (antimalarial and immunosuppressant such as mycophenolate, methotrexate, and azathioprine). Across all endpoints, disease trajectory showed no difference in Asian versus non-Asian patients, supporting Asia-inclusive global SLE drug development. These results describe the first population approach to support a model-informed drug development framework in SLE.

Risk factors for rheumatoid arthritis-associated interstitial lung disease: a retrospective study.

The objective of this study was to assess clinical and imaging features of rheumatoid arthritis (RA) associated with interstitial lung disease (ILD), (RA-ILD) group, in comparison to RA without ILD (RA-C) and to identify the associated factors to ILD. This was a retrospective comparative study (from June 2015 to March 2022) including RA patients aged ≥18 years. The RA-C control group was matched according to age (±2 years), gender, and RA duration (±2 years). General data, RA characteristics, ILD features, and treatment modalities were recorded. Statistical analysis was performed to determine the predictive factors of ILD. A total of 104 patients were included (52 RA-ILD and 52 RA-C); sex ratio was 0.36. Mean age was 66.3±11 years (RA-ILD) versus 65.6±10.8 years (RA-C) (p=0.72). In comparison to RA-C, RA-ILD patients were significantly higher smokers (p=0.01) and physically inactive (p=0.01). Regarding RA features, RA-ILD patients have significantly increased positive anti-citrullinated peptide antibody (ACPA) (p=0.01), ACPA rate (p<0.001), erosive disease (p<0.001), and disease activity score (p<0.001). Mean time to ILD diagnosis was 5.85±7.16 years. Chest high-resolution computed tomography (HRCT) patterns of disease were identified: nonspecific interstitial pneumonia (NSIP) (28.8%), usual interstitial pneumonia (UIP) (17.3%), organizing pneumonia (OP) (25%), acute interstitial pneumonia (13.5%), and respiratory bronchiolitis (3.8%). Multivariate analysis identified smoking, high baseline DAS28 (disease activity score 28) and ACPA positivity as predictive factors of ILD. Our results confirmed the reported associated factors of ILD in RA (smoking, higher disease activity, ACPA positivity). Thus, we need to target the modifiable factors by supporting and educating RA patients to quit smoking and intensify disease modifying anti-rheumatoid drugs (DMARD) to reach remission.

Homocysteine Level Status in Patients with Rheumatoid Arthritis in Duhok: in Relation to Disease. Activity Score

Rheumatoid arthritis (RA) causes high rate of the mortality. Cardiovascular disease (CVD) is markedly elevated in RA partly due to accelerated atherosclerosis (AS) from chronic inflammation. Homocysteine’ elevation (Hcys) strongly related to the AS and CVD’s progression in RA. Current study aims to evaluates Hcys level status and its relation with disease activity (DA) and inflammation marker (CRP) in Duhok RA patients. Sixty-four RA patients (case) were involved in this study with equal number of healthy individuals (control), means± SD of their age were 47.78 ± 14.08 and 46.98 ± 15 respectively. ratio of females to males was (8.1 and 7.0) in case and control respectively. Blood was analyzed and RA related laboratory and biochemical markers were investigated. The results revealed that Means±SD of Hcys was higher in case comparing to control (17.30±8.52 and 7.2±3.4) respectively. RA patient with high DA score recorded higher percentage intra group of increased Hcys level (52%). This study concludes that there is a strong association between Hcys level and RA activity, severity and inflammation process in RA Duhok patients. Hcys could play role as a predictor marker helping physicians for good monitoring and managing RA disease

Homocysteine Level Status in Patients with Rheumatoid Arthritis in Duhok: in Relation to Disease. Activity Score

Rheumatoid arthritis (RA) causes high rate of the mortality. Cardiovascular disease (CVD) is markedly elevated in RA partly due to accelerated atherosclerosis (AS) from chronic inflammation. Homocysteine’ elevation (Hcys) strongly related to the AS and CVD’s progression in RA. Current study aims to evaluates Hcys level status and its relation with disease activity (DA) and inflammation marker (CRP) in Duhok RA patients. Sixty-four RA patients (case) were involved in this study with equal number of healthy individuals (control), means± SD of their age were 47.78 ± 14.08 and 46.98 ± 15 respectively. ratio of females to males was (8.1 and 7.0) in case and control respectively. Blood was analyzed and RA related laboratory and biochemical markers were investigated. The results revealed that Means±SD of Hcys was higher in case comparing to control (17.30±8.52 and 7.2±3.4) respectively. RA patient with high DA score recorded higher percentage intra group of increased Hcys level (52%). This study concludes that there is a strong association between Hcys level and RA activity, severity and inflammation process in RA Duhok patients. Hcys could play role as a predictor marker helping physicians for good monitoring and managing RA disease

Protective Effect of Perilla Oil Against Dextran Sodium Sulfate-Induced Colitis in Mice Challenged with a High-Fat Diet.

This study investigated the effect of perilla oil (PO) on an ulcerative colitis mouse model. Five-week-old male C57BL/6J mice were divided into HD (high-fat diet control), HDD (high-fat diet along with dextran sodium sulfate [DSS] administration), HDD + FO, HDD + PO, and HDD + OO where HDD + FO, HDD + PO, and HDD + OO groups were treated with fish oil (FO), PO, and olive oil (OO), respectively. Biochemical analysis of serum, quantitative polymerase chain reaction, and western blotting of colon tissue were conducted to measure inflammatory marker levels. Administration of DSS resulted in colon shortening and a higher disease activity score than HD group. These symptoms were significantly reversed in the oil-treated groups. The body weight loss after DSS administration was significantly lower in the HDD + PO and HDD + OO groups than in the HDD and HDD + FO groups. PO significantly attenuated the levels of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in the serum and colon. The mRNA expression levels of proinflammatory markers in the colon were reduced, whereas those of tight junction proteins and epithelial defense barrier-associated markers were increased by PO treatment. The protein expression of p-p65 was significantly lower in the PO-treated group than the HDD group. In summary, this study revealed that PO improved colitis in the DSS-induced mouse model, indicating its potential role in managing conditions such as ulcerative colitis.

Foot function in rheumatoid arthritis: Correlation between the Rheumatoid and Arthritis Outcome Score and performance-based physical tests.

Foot function is usually assessed using self-reported outcome measures which remain subjective in patients with rheumatoid arthritis (RA). Physical performance tests were recommended for functional assessment in lower limb osteoarthritis. However, foot function assessment's guidelines in RA are lacking. We aimed to investigate the correlation between a self-reported outcome measure and two performance-based physical tests for assessing foot function in RA patients. A cross-sectional study was performed over 7months' period including RA patients. We used Rheumatoid and Arthritis Outcome score (RAOS) as a self-reported functional tool. Physical performance tests were 4-min walk test (4-MWT) and Timed up and go test (TUGT). Fifty RA patients were included with 96% females and a mean age of 54.7±10.4years. Foot involvement occurred since the diagnosis of RA in 36% of patients. Foot pain was reported by 68% of patients (48% forefoot), and foot stiffness in 46% of patients. Skin lesions of the feet were found in 78% of patients, 90% had foot deformities and 56% had inflammatory disorders of feet. Radiographic lesions were found in 94% of patients. The most impaired RAOS subscales were Sports and Recreation and Quality of life. Poor physical-based performance was found in 34% of RA patients according to 4-MWT, in 42% of RA patients according TUGT, and in 46% of patients based on at least one performance test. RAOS was negatively correlated to the 4-MWT and positively correlated in the subscales pain, other symptoms, activities of daily living, and Sport/Rec of the RAOS. Poor performance-based physical tests were significantly associated with advanced age, sedentary lifestyle, higher disease activity score and impaired functional status. Foot-related parameters significantly associated with poor performance-based physical tests were: foot pain, foot deformity and inflammatory disorders. Multivariate analysis identified foot deformities and higher functional impairment as predictive factors for lower gait speed (4-MWT) and older age and higher functional impairment for higher duration of TUGT. RAOS was significantly associated with performance-based physical function. In the era of connected technologies, these results encourage the regular assessment of rheumatoid foot function by the RAOS score through a connected programme using wearable trackers.

Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R.

Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (TFH) subsets and follicular T regulatory (TFR) cells, in the pathomechanism of the disease. In this study, we aimed to analyze the distribution of the circulating counterparts of these cells and their association with disease characteristics and B cell disproportions in SLE. We found that the increased percentage of activated circulating TFH (cTFH) and cTFR cells was more pronounced in cutaneous lupus; however, among cTFH subsets, the frequency of cTFH17 cells was decreased in patients with lupus nephritis. Furthermore, the decreased proportion of cTFH17 cells was associated with low complement C4 levels and high disease activity scores. We also investigated whether the blocking of the IL-21 receptor (IL-21R) with an anti-IL-21R monoclonal antibody inhibits the B cell response, since IL-21 primarily produced by TFH cells potentially promotes humoral immunity. We observed that anti-IL-21R inhibited plasmablast generation and immunoglobulin production. Our study demonstrated that, besides cTFR/cTFH imbalance, cTFH17 cells play a crucial role in SLE pathogenesis, and modulating cTFH-B cell interaction through the IL-21/IL-21R pathway may be a promising therapeutic strategy to suppress the pathological B cell response.

Pulmonary hypertension in juvenile-onset systemic lupus erythematosus: a case series.

Systemic lupus erythematosus (SLE) is a rare multisystem autoimmune disorder with a variable clinical phenotype. Pulmonary hypertension (PHTN) is a recognised (and not uncommonly asymptomatic) complication of the condition with an associated poor prognosis in adults. It is relatively rare in juvenile-onset SLE (JSLE). We present a retrospective descriptive case series of four female children aged 4 to 15 years at presentation of JSLE and aged 8 to 27 years at time of diagnosis of PHTN from the United Kingdom. All cases were identified through the UK JSLE Cohort Study. Of 665 children with JSLE in the UK cohort study to date (data from 2006-2020), four (0.6%) were identified as having PHTN. 3/4 of the PHTN cases presented with cardiovascular symptoms and / or signs at presentation.3/4 were treated with Rituximab and had a good long-term outcome. Shared clinical features include high baseline disease activity scores. JSLE has a high associated cardiovascular morbidity and mortality and early identification of treatable complications such as PHTN is vital. We suggest that children with high baseline disease activity scores and those presenting with cardiovascular symptoms and signs are most likely to have concurrent PHTN. Routine echocardiography is an effective screening tool and should be used as part of a standard diagnostic work-up.

Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.

The study of autoantibody isotypes in autoimmune diseases is useful for identifying clinically relevant endotypes. This study was undertaken to study the prevalence and clinical significance of different isotypes and IgG subclasses of anti-peptidylarginine deiminase 4 (anti-PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). In 196 RA subjects and 64 healthy controls, anti-PAD4 antibody types were determined using enzyme-linked immunosorbent assay. We investigated associations between anti-PAD4 antibodies and clinical outcomes, and relevant features were confirmed in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG2, anti-PAD4 IgG3, anti-PAD4 IgG4, anti-PAD4 IgA, and anti-PAD4 IgE antibodies were more frequent in RA patients than healthy controls (P < 0.001). Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE were associated with distinct clinical features. Anti-PAD4 IgG1 was predictive of progressive radiographic joint damage (odds ratio [OR] 4.88, P=0.005), especially in RA patients without baseline joint damage (40% versus 0%, P=0.003) or in those negative for anti-cyclic citrullinated peptide and/or rheumatoid factor (OR 32; P=0.009). IgG1 was also associated with higher levels of C-reactive protein (P=0.006) and interleukin-6 (P=0.021). RA patients with anti-PAD4 IgG3 had higher baseline joint damage scores (median Sharp/van der Heijde score 13 versus 7, P=0.046), while those with anti-PAD4 IgE had higher Disease Activity Score in 28 joints (median 4.0 versus 3.5, P=0.025), more frequent rheumatoid nodules (31% versus 16%, P=0.025), and more frequent interstitial lung disease (ground-glass opacification) (24% versus 9%, P=0.014). Anti-PAD4 IgG1 antibody associations with joint damage were corroborated in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE antibodies identify discrete disease subsets in RA, suggesting that heavy chain usage drives distinct effector mechanisms of anti-PAD4 antibodies in RA.

P32 Therapeutic dilemma due to gut complications with spondyloarthritis

Introduction/BackgroundTumor necrosis factor (TNF) inhibitor therapy is one of the primary modalities of treating spondyloarthritis. However, infections secondary to biologic use is a common complication. Clostridium difficile is a gut colonizer which may become pathogenic in the presence of dysbiosis and antibiotic use. Symptomatic clostridium difficile infection(CDI) due to adalimumab(ADA) use causing lymphocytic colitis(LC) is rarely reported. We present a case of axial plus peripheral spondyloarthritis on adalimumab who developed CDI and presented a therapy related dilemma.Description/MethodWe present a case of a 52-year-old lady who was diagnosed as HLAB27 positive axial spondyloarthritis with bilateral sacroiliitis on MRI bilateral sacroiliac joint in 2016. She failed two non-steroidal antinflammatory drugs (NSAID) with high disease activity scores(BASDAI 8.6, BASFI 6.2, Spinal VAS 9). She was eventually initiated on injection adalimumab in 2017. There was clinical improvement after 6 months of initiating ADA. Repeat MRI spine and SI joint showed resolution of inflammatory changes with adalimumab. Sulfasalazine was added in the treatment protocol due to peripheral arthralgia, however she developed a drug rash to it and it was stopped. In September 2021, she developed recurrent non-bloody watery diarrhoeal episodes. Adalimumab was stopped and she tested positive for Clostridium difficile on three occasions. She received multiple courses of vancomycin, fidoxamycin and metronidazole with partial resolution of diarrhoea. Adalimumab was rechallended in January 2022 since her disease activity was worsening in the absence of NSAID and biologic use. However, it was paused again due to worsening of diarrhoea. Gastroenterology conducted a Colonoscopy and biopsy of colonic polyps which showed increased number of intraepithelial lymphocytes with no thickening of subepithelial collagen plate suggestive of lymphocytic colitis (LC). It was postulated that CDI may have been the trigger for her LC. She has been started on local corticosteroid therapy(budesonide) for her LC. At this junction, we were faced with the decision of restarting adalimumab for her which may have been the original cause of her CDI.Discussion/ResultsWe present this case in view of a dilemma regarding which problem occurred first Did immunosuppression due to adalimumab lead to CDI? Literature is not suggestive of increased risk of CDI with adalimumab, especially in a non-inflammatory bowel disease (IBD) background. Was the lymphocytic colitis triggered by the CDI or was clostridium difficile just incidentally detected on a background of LC? There is a well documented associated of LC with autoimmune conditions and use of NSAIDs along with proton pump inhibitor is another trigger for it. TNF alpha inhibitor is one of the treatment modalities of refractory LC. Would it be appropriate to restart ADA for her since she responded well despite there being a risk of recurrence of a CDI? Finally, what is the role of gut dysbiosis in the role of CDI and LC in this situation. Presently, she is planned to be treated with local steroid therapy for her LC. ADA will be rechallenged once her gut has responded to the steroid course. In the event of her gut worsening on a rechallenge, she will be given a trial of Infliximab.Key learning points/ConclusionThe case highlights the crucial point of thinking of causes of diarrhea apart from well documented conditions of ulcerative colitis/Crohn’s disease in an immunosuppressed spondyloarthritis patient. A detailed stool examination including bacterial and parasitic examination is crucial in recurrent diarrhea. The threshold for colonoscopy should be low when episodes are refractory to treatment. The case-based conference gives us an opportunity to receive feedback regarding further management approaches in this case.

The role of ultrasonographic synovial assessment in rheumatoid arthritis patients with concomitant fibromyalgia.

This study aimed to compare the prevalence and musculoskeletal ultrasonography (US) findings of rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) according to the 1990 American College of Rheumatology (ACR) FM classification criteria or the 2016 ACR FM diagnostic criteria. This cross-sectional study included 63 patients (17 males, 46 females; mean age: 48.2±7.1 years; range, 18 to 62 years) with RA. Medical history and laboratory data were obtained from electronic records. Clinical examination, composite disease activity measures, functional status, and the German 7-joint ultrasound score were assessed to evaluate disease activity and synovial inflammation. The patients were divided into three groups: patients who met only the 2016 ACR criteria, patients who met only the 1990 ACR criteria, and patients who met both criteria. In patients with RA, concomitant FM prevalence was 34.9% according to the 2016 ACR FM diagnostic criteria versus 23.8% according to the 1990 ACR FM classification criteria. Rheumatoid arthritis patients with FM had high tender joint count and disease activity scores, while musculoskeletal US findings were similar. Patients who met only the 2016 ACR FM diagnostic criteria had significantly higher gray-scale US and power Doppler US synovitis scores than patients who satisfied only ACR 1990 FM classification criteria (p=0.03 and p=0.02, respectively). Synovial inflammation is a prominent sign in RA patients diagnosed with FM according to the 2016 ACR FM diagnostic criteria. The higher disease activity seen in the presence of FM in RA patients is associated with FM rather than synovitis.

Assessment of Quality of Life among Patients with Periphera Spondyloarthropathy

Background: Peripheral spondyloarthropathy refers to spondyloarthropathy with predominant peripheral (arthritis, enthesitis or dactylitis) involvement which leads to significant disability. Objective: To assess the quality of life in patient with peripheral spondyloarthropathy (pSpA). Methodology: The study was a cross sectional study conducted in the Department of Physical Medicine and Rehabilitation, BSMMU, Dhaka, from March 2021-February 2022. A total of 105 patients diagnosed with pSpA attending the study place were purposively selected for the study. Patients with concurrent systemic inflammatory rheumatic disease such as RA, SSc, lupus, Dermatomyositis were excluded from the study. Disease activity was measured by the validated Bengali version of The Ankylosing Spondylitis Disease Activity Score (ASDAS), including C-reactive protein (ASDAS-CRP) while health related quality of life was assessed by the validated Bengali version of Short Form Health Survey (SF) 12v2 instrument. Results: The mean age of the study participants was 38.8(±9.8) years where 68 (64.8%) were male. The mean duration of disease was 4.3(±3.3) years where 55 (52.4%) had up to 3 years’ duration of disease. The mean ASDAS-CRP was 3.9 ±0.8 where 69(65.7%) had very high Disease Activity Score. All (100.0%) study participants had arthritis and inflammatory back pain. HLA B27 was present in most of the study participants (N=101, 96.2%) and 99 (94.3%) had enthesitis. The mean Physical Component Summary (PCS) and Mental Component Summary (MCS) was 34.0(±7.8) and 41.3 (±7.7) respectively. There was weak negative correlation between age and PCS of SF-12 scores (r=-0.233, p=0.017). There was negative correlation between duration of the disease and PCS of SF-12 scores (r=-0.339, p&lt;0.001) and MCS (r=-0.290, p=0.003). Again, there was moderate inverse correlation ASDAS-CRP and PCS of SF-12 scores (r=-0.406, p&lt;0.001) and MCS of SF-12 scores (r=- 0.461, p&lt;0.001). Conclusion: Majority of the patients .....