Posters Abstracts



   Table of Contents   POSTER ABSTRACT Year : 2022  |  Volume : 17  |  Issue : 5  |  Page : 25-203

Posters Abstracts

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Date of Web Publication26-Nov-2022

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DOI: 10.4103/0973-3698.362016

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,. Posters Abstracts. Indian J Rheumatol 2022;17, Suppl S1:25-203
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Myofibroblast and pro-fibrotic cytokines in fibrosis of IgG4-related disease patients from South Asia: Preliminary data

Josna Joseph, V Prabhu, Meera Thomas1, K Rekha2, Thomas Alex1, John Mathew*; Departments of Clinical Immunology and Rheumatology, 1Pathology and 2Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India

Background: Myofibroblasts are specialized, activated fibroblasts found generally in fibrotic tissue and has excessive collagen secretion and contractile properties. There exists a paucity of data on the mechanistic role of pro-fibrotic cytokines in Indian IgG4-RD patients. Efficient treatment strategies could be devised, if the exact pathomechanism of myofibroblast activation in IgG4-RD associated fibrosis could be known.

Objective: To analyse ambispectively the presence of myofibroblasts and pro-fibrotic cytokines, IFN gamma and IL-33 involved in IgG4-RD associated fibrosis by immunohistochemical staining of biopsy samples from South Asian patients.

Methods: Archived biopsy samples of definite/ probable/ possible cases of IgG4-RD, classified according to classification criteria (1), taken from patients who attended the OPD and IPD of our tertiary care centre during January 2015 – January 2020 (12 nos.) were selected for this study. The paraffin sections were examined qualitatively for fibrosis and the excessive collagen deposition by histological staining like Hematoxylin and Eosin, Masson's Trichrome. Also, semi-quantitatively for the presence of alpha-Smooth muscle actin (α-SMA) expressing myofibroblasts and the involvement of pro-fibrotic cytokines (IFN-gamma, IL-33) by Immunohistochemistry. The presence of myofibroblasts and fibrogenic cytokines detected was semi quantitatively scored (+mild, ++moderate, +++ severe) and analysed.

Results: In the biopsy tissue sections of classified cases of IgG4-RD, myofibroblasts were present in 10/12 patients, moderate levels in 4 (33%) and very high (+++) in 3(25%). When IFN-gamma expressed at low levels in 6 (50%) and absent in 6 (50%), all the patients showed IL-33 expression with very high levels in half of the samples (6, 50%).

Conclusion: Profibrotic cytokine, IL-33 shows upregulation in the biopsy samples of IgG4-RD patients, suggesting a plausible role in fibrosis regulation. Further studies are warranted to identify earlier markers of fibrosis onset.

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Prevalence of LTBI in patients with autoimmune diseases and in general population and specificity of Interferon Gamma Response Assay

Yogitha Chennault, S Chandrashekara, P Renuka; ChanRe Rheumatology and Immunology Centre and Research, Bengaluru, Karnataka, India

Background and Aims: In India, there are limited information on the prevalence of LTBI in the Autoimmune rheumatic disease population. To estimate the prevalence of LTBI positivity by Interferon gamma response assay (IGRA) among the patients with ARD and to compare the predictability of Tuberculosis in patients exposed to biologicals.

Methods: A retrospective database study, 1064 patients who were tested with IGRA from 2019 to 2022, were collected. The primary diagnosis, IGRA results and the Tuberculosis relapse during the follow-up with biologic exposure were collected.

Results: Among 1064 patients were tested, 941 for pre-assessment to biologics and 121 to exclude TB and 2 were excluded from analysis. IGRA was positive in 125 (13.28%) biologic screening and 40 (33.06%) when tested for TB screening and 816 (86.72%) patients screened for biologics were negative and 81 (66.94%) were suspects. 9 (0.85%) patients, developed active TB out of which 6 were screened for biologics and 2 (33.3%) were positive and 1 received prophylaxis and 4 (66.7%) negative and received biologics. 3 out of 9 were suspected and have developed active TB in 2 (66.67%) with IGRA negative out of which 1 had past TB infection and 1 (33.33%) with IGRA positive had developed active TB. Specificity of the IGRA in patients receiving biologics is 97.25% and in suspects is 66.95%. [Table 1].

Conclusion: In patients who received biologics, 6 out of them have developed a flare out of which 4 (66.67%) were negative and 2 patients have developed flare despite prophylaxis out of which 1 had received prophylaxis after biologics in view of high disease activity. In suspected patients, 3 have developed active disease and out of which 1 had positive IGRA and had developed active disease despite prophylaxis and in 2 patients with IGRA negative, 1 had past TB infection.

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Rheumatology training in India: What needs to be done: A consultant perspective

Divya Lala1,2, Kunal Patil3, Yojana Gokhle4; 1Department of Rheumatology, Reliance Hospital, 2Department of Rheumatology, Fortis Hospital, 4Department of Rheumatology, Lokmanya Tilak Municipal Medical College, Sion Hospital, Mumbai, 3Sanjivani Rheumatology Clinic, Dr D. Y. Patil Medical Collage, Kolhapur, Maharashtra, India

Background: Rheumatology is an emerging specialty of medicine in India. Rheumatology training needs to be structured and comprehensive. We surveyed rheumatology consultants regarding their perception and perspectives about rheumatology training in India.

Objectives: This study was aimed to explore the unmet need for improvement in training and the changes that need to be introduced to improve the training.

Methods: An online questionnaire was circulated virtually to randomly chosen rheumatology consultant across India. Questionnaires had fixed responses as well as open end responses which was designed to assess duration of rheumatology training, interdepartmental rotation, procedure needs to be trained, development of structured referral system and structured programme of rehabilitation etc.

Results: The questionnaires were virtually sent to 80 consultants among which 52 responded (52/80). Mean duration practice experience was 10.4 (+/-6.2) most of being from private setup (40/52). 70% consultant underwent training in India.58 % responded that duration of training should be of 3 year.100% respondent felt that there should be rheumatology training in UG and PG training days. Other department rotation included in curriculum should be biochemistry (92%), radiology (92%) physiotherapy (82%) occupation therapy (52%). 84% respondent felt there should be exchange programme amongst Indian institution. 76 % respondent felt there need of training for structured programme for rehabilitation.

Conclusion: Rheumatology training in India can be improved by training during UG and PG curriculum. There should be interdepartmental rotation during rheumatology training. There should be uniform curriculum across India along with exchange programme amongst institution.

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Oxidative stress and inflammation in healthy subjects residing in polluted zones of a metropolitan city in India: A cross-sectional study

Uma Kumar, Maumita Kanjilal, Maheswari Thangavelu, Lakshmy Ramakrishnan1; Departments of Rheumatology and 1Cardiac Biochemistry, All India Institute of Medical Sciences, New Delhi, India

Background: Air pollution is an important factor risk factor for oxidative stress and inflammation leading to immune response.

Objectives: To study the prevalence of oxidative stress and inflammation in healthy subjects residing in the most polluted zones of Delhi -NCR.

Methods: A cross-sectional study was conducted on healthy subjects between 18 to 60 years of age, residing in highly air polluted zones of Delhi NCR, India for the past 10 years and whose houses were within a one-kilometre radius distance from the air quality monitoring stations. AIIMS Human Ethics Committee approved the study. Pregnant and lactating females were excluded.

Results: 350 healthy subjects were recruited. The mean age of subjects was 37.09±9.65 years with male-to-female ratio being 1:1. The mean body mass index (BMI) was found to be 25.83 ± 5.25 kg/m2. The inflammatory markers IL-6, TNF-α, and Hs-CRP were elevated in 87% (306/350), 15% (54/350) and 17% (61/350) subjects respectively. Markers of oxidative stress were elevated in 76% of subjects; Malondialdehyde (MDA) in 68% (239/350) and total oxidant status (TOS) in 76% (266/350) while both were elevated in 54% (190/350) subjects. Antioxidant total antioxidant status (TAS), Glutathione (GPX1) and superoxide dismutase (SOD) were reduced by 66% (230/350), 9% (31/350) and 36% (127/350) subjects respectively. There was a positive correlation between IL-6 and TOS and a negative correlation between IL-6 and TAS. Correlation of IL-6 with markers of oxidative stress OSI shown in [Table 1].

Table 1: Spearman-rank correlation coefficient analysis of IL-6 with markers of oxidative stress

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Conclusion: 76% subjects residing in the selected polluted zones of Delhi, NCR had elevated levels of TOS while 87% participants had elevated inflammatory markers reinforcing the fact that oxidative stress and inflammation are interconnected. Individuals between the age group 18-40 years were more prone to oxidative stress due to their more outdoor activities.

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To study correlation between seropositivity and disease severity in rheumatoid arthritis

K P Rohith, J Deepthy, M Gautam1, Ramakant1; Departments of General Medicine and 1Indian Navy Hospital Ship Asvini, Mumbai, Maharashtra, India

Background: The rheumatoid factor (RF) and anti- citrullinated protein antibodies (ACPA) blood test is the most commonly adopted test for the diagnosis of rheumatoid arthritis (RA). RA patients who are seropositive for RF and/or ACPA face a greater likelihood of developing more aggressive symptoms.

Objectives and Methods: Our goal was to study the demographic, clinical characteristics and disease severity, as well as their correlation with RF or/and ACPA seropositivity, among a series of 61 RA patients aged >18 years who attended rheumatology clinic at INHS Asvini, Mumbai.

Results: Of the 61 RA patients included in this study all were male. Demographic data: Mean age of population was 40.84 +/- 10.40 years, Habits: Smoking-17 (27.8%) and Alcohol-16 (26.2%), 23 patients had comorbidities. Average duration of RA was 4.13 years (SD: 3.97). Forty patients were seropositive (RF positive: 32, CCP positive: 22, both positive: 15) and 21 were seronegative [Table 1]. Twenty-two (36.1%) patients had abnormal findings on X-ray of hand at the time of evaluation. Subcutaneous was the most common extra articular manifestation seen in 7 (11.5%), one each had ILD and colitis, none had red eye/dry eye or dry mouth [Table 2]. Skeletal deformity was present in 13 patients. Mean with SD of ESR, CDAI and DAS 28 was -18.70 mm Hr (12.362), 11.549 (10.3335) and 4.467 (6.7795) respectively. cDMARDs: 93.4% patients were on methotrexate therapy, 37.7% and 9.8 % were on hydroxychloroquine and leflunomide therapy respectively. Almost 64% of patients were on steroid therapy. bDMARDs usage was seen in about 36% patients. No significant associations between seropositivity and disease severity was seen based on CDAI and DAS 28 scoring system (Coefficient: 0.204, p value: 0.17). However mean CDAI and DAS 28 score was higher in seronegative group. (10.038 vs. 14.429, 3.396 vs. 6.229).

Table 1: Clinical disease activity index and disease activity scores 28 scoring in seropositive and seronegative group

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Conclusion: RF and ACPA seropositivity and seronegativity status RA patients were found to have similar disease severity based on articular- extra articular manifestations, CDAI and DAS 28 scoring system. Both scoring systems had similar results in both groups.

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Study on monitoring of methotrexate liver toxicity with ultrasound abdomen in rheumatoid arthritis: A retrospective observational study

Anjana G Varier, Hima Sreekumar, S R Lekshmi, Vishad Viswanath; Institute for Rheumatology and Immunology Sciences, Thiruvananthapuram, Kerala, India

Background: Methotrexate has been the anchor drug for treatment of Rheumatoid Arthritis (RA) for decades. Hepatic fatty infiltration, fibrosis with a potential to progress to cirrhosis, is one of the most severe adverse effects of long-term methotrexate treatment. Concerns about hepatotoxicity has led to the implementation of guidelines for intensive monitoring, including the use of surveillance liver biopsy, imaging and liver function tests at regular intervals of methotrexate treatment. In this Study we look at the utility of screening Ultrasound Abdomen in monitoring of methotrexate liver toxicity.

Objective: To assess the Outcome of screening Ultrasound Abdomen in monitoring of liver toxicity in Rheumatoid Arthritis patients on Methotrexate.

Methods: This study is a retrospective Observational study of RA patients under follow-up in our institution. Seropositive RA patients with atleast one Ultrasound Abdomen done during treatment period were selected. The Outcome was assesed as Stopped, Tapered or continued methotrexate according to Ultrasound liver finding.

Results: 60 patients were studied. The mean age of patients were 52 years with mean duration of illness 10 years. Mean duration of treatment was 3 years.12 patients stopped methotrexate treatment based on USG finding out of which 2 patients had Grade I fatty liver with transaminitis, 1 patient had Grade II fatty liver with transaminitis, 4 patients had Grade II fatty liver without transaminitis, 1 patient had grade III fatty liver with transaminitis, 2 patients had cirrhosis with transaminitis and 2 patients had cirrhosis without transaminitis. 58% of patients who stopped methotrexate had cumulative dose less than 1500 mg of methotrexate.

Conclusion: Chronic liver disease can occur with normal liver function tests. Periodic screening of RA patients with Ultrasound abdomen during treatment could help in reducing risk of long term methotrexate liver toxicity.

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Disease perceptions, anxiety and depression in patients with rheumatoid arthritis: A cross-sectional study

P M Ankush, Nishant G Kamble, Sayan Mukherjee, Abilash V Krishnan, Mukesh K Maurya, Urmila Dhakad; Department of Clinical Immunology and Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India

Background: Rheumatoid arthritis (RA) is the most common autoimmune arthritis worldwide. Treatment of RA includes pharmacotherapy and physical therapy. Research based on Leventhal et al's common-sense model of illness has shown that the way patients make sense of their disease can strongly influence their quality of life. Depression and anxiety are also associated with functional disability and pain perception of RA patients.

Objectives: To study Disease Perceptions and prevalence of Anxiety and Depression in patients with RA.

Methods: Patients diagnosed with RA as per ACR 2010 criteria, attending OPD were interviewed. Pregnant females, patients with infections, psychiatric disorder, CKD, Heart Failure, chronic lung and liver disease were excluded. Disease perception was measured using Brief Illness Perception Questionnaire (BIPQ) (Total Score 0-80). Anxiety and Depression were assessed using Hospital Anxiety and Depression Questionnaire (HADS).

Results: A total of 78 patients were interviewed. Mean age was 41.6 years and 89% of them were females. 35.8% patients had low disease activity or were in remission and 74.2% patients had moderate to high disease activity. 53.8% had either borderline or abnormal anxiety score and 51.2% patients had borderline or abnormal depression score. Mean total BIPQ was 45.05 and item 6 on BIPQ (patients concern) had highest mean score of 8.06, followed by item 8 (emotional impact) (i.e., 7.18). Mean score for item 4 (impact of treatment) was the lowest (2.36).

Conclusions: Half of our patients had borderline or abnormal anxiety and depression score. Patients were greatly concerned and emotionally disturbed due to the illness. On the positive side, their perception about benefit of treatment was really good. Poor perception, anxiety and depression contribute to poor quality of life, treatment adherence and functional disability. There is a dire need for interventions specifically targeting these issues.

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Safety of tacrolimus in patients with rheumatoid arthritis associated interstitial lung disease

Sharath Kumar, Vikramraj K Jain, S Nagaraj, D Ranjitha, V A Deepika Ponnuru; Optima Super Speciality Hospitals, Bengaluru, Karnataka, India

Background: Tacrolimus has proven effective for rheumatoid arthritis and Myositis-ILD. However, knowledge of its utility in RA -ILD is restricted to only 2 publications from Japan. We analysed data of RA-ILD patients from our centre who were on tacrolimus to determine the safety and efficacy of the same.

Objectives: To determine safety of tacrolimus in patients with RA-ILD as well as outcomes (mortality, respiratory admission).

Methods: Retrospective review of RA-ILD patients from our centre treated with tacrolimus between January 2015 and July 2021. Patients demographic details, duration of ILD, any hospitalisations due to respiratory illness, worsening of serum creatinine, development of diabetes and HTN during the study period were determined. In addition, the requirement of oxygen and steroids at the last follow up visit and deaths were recorded and analysed.

Results: Twenty-four of 35 RA-ILD patients were treated with Tacrolimus. Patient characteristics are mentioned in [Table 1]. During cumulative follow up 85 patient-years none experienced worsening of serum creatinine. Diabetes and HTN was diagnosed de-novo in 3/15 (20%) and 7/15 (46.7%) patients respectively. Most patients were off supplemental oxygen at last follow-up (20/24). Half on daily steroids at last follow up, most on.

Table 1: Characteristics of rheumatoid arthritis associated interstitial lung disease patients treated with tacrolimus

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Conclusion: In this data set, tacrolimus seemed to be safe in RA-ILD with no cases of nephropathy. Development of HTN as well as diabetes due to the medication is a concern. Most patients at last follow-up had not had respiratory admissions, were alive and off supplemental oxygen. However, lack of follow up PFTs and lack of comparative group makes any inference of efficacy tenuous at best. Prospective randomized controlled studies are needed.

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Therapeutic impact of curcumin on inflammation and endothelial dysfunction in adjuvant induced arthritic rats: CiRA study

Inderjeet Verma, Manni Rohilla, Ashit Syngle1, 2, 3, Devaansh Syngle3, Anmol Singh Bains3; M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, Haryana, 1Healing Touch City Clinic, Chandigarh, 2Fortis Multi Specialty Hospital, Mohali, Punjab, 3Healing Touch Foundation, Chandigarh, India

Background: Cardiovascular disease is leading cause of death RA due to increased CV risk resulting from inflammation-induced endothelial dysfunction and accelerated atherosclerosis. The management of this enhanced CV risk in RA is still evolving.

Objective: To investigate the impact of Curcumin on endothelial function in Adjuvant Induced Arthritis animal.

Methods: Arthritis was induced in Wistar rats by complete Freund's adjuvant (FCA), and treated with curcumin (150 and 300 mg/kg/day) and methotrexate (7.5 mg/kg/week) after onset of arthritis (day 21) until day 42. The effects of curcumin were assessed by arthritis score, inflammatory serum cytokines, oxidative measures as well as histological changes in aorta of Wistar rats.

Results: Curcumin (150/300 mg/kg) had significant impact on arthritis score, paw thickness, ESR and CRP level in Wistar rat as compared to disesae control group while curcumin 300 mg/kg has shown almost similar to MTX treated group. Curcumin (300 mg/kg) also reduced pro-inflammatory cytokines – TNF-α, and IL-6, which levels were close to MTX treated group. We also found that both the doses of curcumin demonstrated substantial improved oxidative measures like superoxide dismutase (SOD) and glutathione (GSH) level as well as a significant decrease in nitric oxide (NO) levels compared with disease control. Interestingly, the level of NO, SOD and GSH was slightly more improved in curcumin 300 mg/kg group than the MTX treated group. The protective effect of curcumin on endothelial function was also evident from the histological changes in aorta [Figure 1] and its effect was found comparable to that of MTX treated animals.

Figure 1: Histopathological images of the aorta of Wistar rat in different experimental groups. Histopathology findings that normal control group. (a) The normal endothelial cell are present on the endothelial layer without any destruction in the endothelium layer. Disease control group. (b) Abnormality in the endothelial cell on the endothelial layer in this figure endothelial cells are less and become flat which are the sign of destruction in the endothelium. MTX treated group. (c) Minimum destruction in the endothelium and some some endothelial cells are flat VC treated group. (d) Also abnormality in the endothelial cells on the endothelium in which endothelial cells are became less and flat due to destruction on the layer CRM 150 mg/kg dose group. (e) The endothelial cells are normal along with some minimum flat cells. CRM 300 mg/kg dose group (f) The normal and more cells are present on the endothelium, there is no destruction in the cells and endothelium was measured as normal

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Conclusion: This is the first study to explore the impact of curcumin on endothelial dysfunction in RA. This current study demonstrated that AIA experimental rat's treatment with curcumin (150/300 mg/kg/day) has anti-inflammatory, antioxidant and vasculo-protective potential. Curcumin 300 mg/kg/day) has extremely similar therapeutic impact with MTX. However, further pharmacological investigations are warranted.

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A molecular docking and simulation study targeting STAT-I through active phytocompounds of Curcuma caesia

Ankita Pati, Jyoti Ranjan Parida, Dattatreya Kar, Ananya Kuanar; Centre for Biotechnology, Siksha 'O' Anusandhan University, Bhubaneswar, Odisha, India

Rheumatoid Arthritis is a chronic, inflammatory, and systemic autoimmune disease, it affects people worldwide, where higher production of Signal transducer and activator of transcription 1 (STAT-I) is associated with this form of the disease. Traditionally used medicinal plants contain a large amount of bioactives and pave a new path to develop drugs and medications for Rheumatoid Arthritis. Curcuma caesia is an endangered plant endemic to North-East and Central India that has several medical applications such as bronchitis, dysentery, diarrhoea, tumours, cancer, and cosmetic applications as [Figure 1]. Curcuma caesia's biological and therapeutic activities have been attributed mostly to its bioactive ingredients such as camphor, curcuminoids, phenolics, flavonoids, protein, amino acids, essential oil, and alkaloids. In reality, the primary ingredient, camphor, curcuminoids, has been linked to a variety of pharmacological actions that can be used to treat arthritis and its accompanying inflammatory responses. The present study was aimed to examine the potential of Curcuma caesia bioactive compounds against STAT-I. Interferons (IFNs) and other cell signals are known to be the major reason behind the activation and production of human STAT-I by translocating to the nuclei and activating transcription of IFN-stimulated genes. In this study, 72 compounds from Curcuma caesia were taken based on traditional knowledge linkage with inflammatory-like disease treatment, were screened against the Homology-Modelled structure of STAT-1 with the objective of identifying some active phytochemicals as inhibitors. The entire study was carried out using AutoDock Vina 1.2 and different modules of Schrodinger Suite 2020-3. During the docking of the phytochemicals, a compound, Delta-Cadinene from Curcuma caesia showed the best binding affinity with the receptor with a Docking Score of −7.3. In order to study the binding stability, the complex between the STAT-1 and Delta-Cadinene was subjected to 100 ns Molecular Dynamics simulation using Desmond module of Schrodinger suite 2020-3, during which the receptor-ligand complex showed substantial stability after 50 ns of MD Simulation [Figure 2]. The phytocompound Delta-Cadinene also showed promising results during ADME-Tox and bioactivity score prediction analysis performed using Swiss ADME, pkCSM, ProTox II and Molinspiration servers, respectively. The compound Delta-Cadinene is suggested as a potential STAT-1 inhibitor based on the results of this analysis, which may then block the immunosuppressive mechanism in the human body during the start of the disease. Further research built on this study would pave the way for the accurate and long-lasting identification of a viable therapeutic regimen for the treatment and management of rheumatoid arthritis.

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Can we predict response to methotrexate in rheumatoid arthritis: Results from a multicentre, randomized controlled trial on methotrexate escalation in rheumatoid arthritis

Siddharth Jain, Varun Dhir, Amita Aggarwal1, Ranjan Gupta2, Bidylaxmi Leishangthem, Shankar Naidu, Aastha Khullar, Veena Dhawan3, Shefali Khanna Sharma, Aman Sharma, Sanjay Jain; Department of Internal Medicine, Division of Clinical Immunology and Rheumatology, Postgraduate Institute of Medical Education and Research, 3Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 2Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India

Background: Methotrexate (MTX) is the gold standard, first-line therapy for rheumatoid arthritis (RA). However, not all patients respond to MTX, and the predictors of its response or non-response have not yet been reliably identified. Identification of these predictors will facilitate personalized therapeutic choices, and improve patient outcomes.

Objectives: To identify clinico-laboratory predictors of response to MTX monotherapy in active RA.

Methods: This study included patients with active RA (SJC ≥2 and TJC ≥4) aged 18-55 years, with disease duration <5 years, who were not receiving DMARDs (except HCQ and low-dose prednisolone) and had been enrolled in the multicentre, parallel group RCT comparing two different MTX escalation strategies in RA (MEIRA). All these patients received MTX monotherapy which was started at 15 mg/week, escalated to 25 mg/week by 4-8 weeks, and continued till 16 weeks. MTX response was defined as EULAR good or moderate response (based on DAS28-3v) at 16 weeks. Stepwise, multivariable logistic regression was done using key demographic (age, gender, BMI, comorbidities), clinical (disease duration, DAS28, HAQ), and laboratory parameters (RF, anti-CCP, ESR, CRP, RBC MTX-polyglutamates, IL-6, MMP-3) as independent variables to identify predictors of MTX response. Two-tailed p-value <0.05 was considered statistically significant. (Trial Reg: CTRI/2018/12/016549).

Results: Out of a total of 178 included patients [84% females, mean age 40 (9) years, mean DAS28-CRP=5.4 (1.1)], 113 (63.5%) were classified as MTX responders at 16 weeks. Age (OR=0.95, p=0.01), BMI (OR=1.12, p=0.006), and RF (OR=0.34, p=0.045) were found to be independent predictors of MTX response on multivariate analysis [Table 1]. On sensitivity analysis with DAS28-ESR-based EULAR response, age (OR=0.94, p = 0.003) and RF (OR=0.42, p = 0.059) were replicated as independent predictors of MTX response, in addition to pre-treatment swollen joint count (OR=0.94, p = 0.05).

Table 1: Multivariable logistic regression analysis for prediction of methotrexate response (European league against rheumatism good or moderate response based on disease activity scores 28 -C-reactive protein) in rheumatoid arthritis

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Conclusion: Younger age, RF negativity, higher BMI, and lower pre-treatment swollen joint count are potential predictors of response to MTX monotherapy in RA.

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Self-assessment of joints in RA: Is it worth pressing for?

S Sri Lakshmi, Sandeep Kansurkar, Deepti Agarwal, Kavita Krishna; Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India

Background: Self-assessment of joints by patients, if reliable and accurate can be used as a potential clinical tool in rheumatoid arthritis. Traditionally, joint examination is done by clinicians. However, patient self-joint count is explored in this study to incorporate the technique in day-to-day clinical practice. The utility of patient self-joint counts has become an increasingly important area to explore, with remote disease monitoring and telehealth taking on a larger role across rheumatology practices in this global pandemic. This study is inspired from the video released by Centre for Epidemiology and Arthritis on self-assessment of joints in patients with RA.

Objectives: This study aims to assess the joint involvement by patients and compare it with clinician in terms of accuracy to include the same in routine clinical practice as a diagnostic tool.

Methods: Consecutive rheumatoid arthritis patients over the age of 18 were included in this study. Total sample size was 43. Patients were given an instruction manual on how to examine the joints in English and regional language. If the patient had difficulty in reading, the attendant was allowed to explain the same to the patient. Then patient filled a form with pictorial representation of the joints and joints with swelling and pain was marked. They also scored the pain, difficulty of the questionnaire and patient global assessment score. This was followed by clinician assessment and physician global assessment.

Results: The total number of joints involved as counted by the clinician was 499 and by the patient was 559. The sensitivity was 86.02 % (82.6- 88.9%) and specificity was 95.62 % (94.8-96.3%) [Table 1]. Among the joint examination, the patient assessment of shoulder (Sp- 91.95%) and elbows (Sp-96.18%) was perceived better by the patient [Figure 1]. Whereas more distal joints like wrist, MCP, Knee and ankle was perceived more accurately by the clinician. There was high false positivity rate with MCP and PIP joints.

Table 1: Sensitivity and specificity of joint examination: Self-assessment of rheumatoid arthritis

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Conclusion: This study shows that self-assessment of joints by patient is a reliable tool in monitoring disease activity.

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Evaluation of myocardial function in patients with rheumatoid arthritis using strain ECHO and correlation with duration of disease and disease severity

Kavitha Mohanasundaram, G S Sanjay Surya, Sanjeeiv Krishnan, Gowtham Hanumanram, A Gowrishankar; Saveetha Medical College, Chennai, Tamil Nadu, India

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterised by chronic inflammatory changes. Pro inflammatory cytokines released in RA has a negative impact of cardiac health. Individuals with RA have shorter life expectancy and their risk of cardiovascular death is more than 50 % higher than that of the rest of the population. Early myocardial dysfunction in RA patients may be detectable sooner using speckle-tracking echocardiography.

Materials and Methods: This cross sectional study was conducted in 65 patients with rheumatoid arthritis and 65 healthy controls (mean age = 36 years) at a tertiary health care centre. Two-dimensional and Doppler echocardiograms were performed on all subjects by a single ECHO operator. Strain analysis was done by speckle-tracking echocardiography. Statistical analyses was performed by using a statistical software package SPSS, version 20.0.

Results: The mean Global Longitudinal Strain values in rheumatoid arthritis patients was lesser than controls and it was statistically significant [p =0.001, [Table 1]]. Duration of RA when more than 5 years had significant impact on GLS and had reduced GLS when compared to subjects whose disease duration was less than 5 years of disease [Table 2]. Presence or absence of erosions did not change GLS. No statistical difference was noted when GLS was compared in patients with seropositive and seronegative rheumatoid arthritis.

Table 1: Comparison of demographic, acute-phase reactants and speckle-tracking echocardiography between case and control by Student's t-test

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Table 2: Comparison of global longitudinal strain with disease duration, erosions, rheumatoid factor and anti cyclic citrullinated peptides positivity in rheumatoid arthritis

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Conclusion: Patients with RA and no clinical Cardiovascular disease have reduced Left ventricular systolic function as shown by lower Global Longitudinal Strain. It is associated with disease activity and RA disease duration. Routine Speckle-tracking method can be employed regularly in RA patients for early detection and treatment.

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Comparison of two schedules for administering oral methotrexate (split dose vs. single dose) once weekly in patients with active rheumatoid arthritis: An open label, parallel group, randomized controlled trial split-dose methotrexate in active rheumatoid arthritis trial

Chandra Bhushan Prasad, Varun Dhir, Bidyalaxmi Leishangthem, Aastha Khullar, G S R S N K Naidu, Priya Saini, Shefali Khanna Sharma, Aman Sharma, Sanjay Jain; Department of Internal Medicine, Clinical Immunology and Rheumatology Unit, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Background: Methotrexate (MTX) is a well-known anchor drug for rheumatoid arthritis (RA). Splitting the oral MTX (>15 mg per week) is an option to improve its bioavailability as well as efficacy.

Objective: To compare the efficacy, safety and tolerability of split-dose versus single dose once weekly regimen of oral MTX in patients with active RA.

Methods: SMART is ongoing 24-week multicentre, open-label (assessor blinded) RCT which proposes to enroll 250 patients age 18-60 years having active RA with disease duration <5 years. Here we present 16-week data from single centre. Patients were randomized 1:1 into either oral split-dose MTX (10 mg in morning and 15 mg in evening on same day once a week) or oral single dose MTX (25 mg once a week) regimen. Primary outcome was EULAR response (either good or moderate response) at 16 weeks [Table 1]. Analyses were intention-to-treat.

Table 1: Outcome between the two groups at 16 weeks (intention-to-treat using worst case imputation)

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Results: 50 patients (46 females) were randomized to split (n=26) or single (n=24) dose group. At 16 weeks, there was no significant difference in proportion of responders in split (84.6%) or single (66.4%) dose groups (p=0.14). Proportion of good responders was also not significantly different at 16 weeks (46.2%, 20.8%, p=0.06). However, there was significantly higher SDAI based remission (26.9%, 4.2%, p=0.048) and mean ΔDAS28-CRP (-2.3, -1.3, p=0.01) in the split-dose compared to single dose group. There was no significant difference in the ΔIHAQ and SDAI-LDA between groups. There was no difference in cytopenia, transaminitis or MTX intolerance between the two groups. No death or serious Adverse effects were seen. Serum MMP-3 declined in both groups but was not statistically different between the groups.

Conclusion: In this interim analysis there was no significant difference in primary efficacy outcome or tolerability or Adverse effects between split-dose compared to single dose oral MTX. However, some secondary outcome favored split-dose in terms of efficacy, which needs to be explored. Trial registration number: CTRI/2021/02/03136.

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Expert consensus on rheumatoid arthritis patients' profiles most likely to benefit from Baricitinib treatment

Chamaida Plasencia, Andrés Navarro1, Raimón Sanmartí2, José María Álvaro-Gracia3,4, Marta Comellas5, Clara Gabás-Rivera5, Sebastián Moyano6, Silvia Díaz6, Mercedes Núñez6, K B Rakesh7; Servicio de Reumatología, Hospital Universitario La Paz, Paseo de la Castellana, Madrid, 3Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Calle del Doctor Esquerdo, Madrid, 4Universidad Complutense de Madrid, Avenida Séneca, Madrid, 6Department of Medical, Lilly Spain, Av. de la Industria, Madrid, 1Servicio de Farmacia, Hospital General Universitario de Elche, Carrer Almazara, Elche, Alicante, 2Servicio de Reumatología, Hospital Clínic, Calle de Villarroel, Barcelona, 5Outcomes'10, Universitat Jaume I Parc Cientific Tecnológic i Empresarial Edificio Espaitec Avenida sos Baynat s/n, Castellón de la Plana, Castellón, Spain, 7Eli Lilly and Company (India) Pvt. Ltd., Gurugram, Haryana, India

Background: Baricitinib was approved in Spain for treatment of moderate-severe RA in adult patients with inadequate response/intolerance to disease-modifying antirheumatic drugs (DMARDs).

Objectives: Identifying profiles of RA patients that would obtain the greatest clinical benefit from baricitinib treatment.

Methods: Expert consensus based on Delphi methodology. The questionnaire used was developed based on review of scientific literature on baricitinib treatment in RA, a working group of experts and review of 3 rheumatologists, 1 pharmacist and 1 patient. It contained socio-demographic variables and 31 statements (58 items) regarding possible patient profiles for treatment. Participants expressed level of agreement with statements using 9-point Likert scale. Consensus was established when ≥75% participants scored a question in the range of disagree (items 1-3)/agree (7-9). Questions not reaching consensus were re-evaluated in a second round.

Results: 20 experts (mean age 52.8 [SD: 8.5] years, 55% women, 65% rheumatologists, and 35% hospital pharmacists) completed the 2-rounds. Consensus was reached in 69% of items. Participants agreed that baricitinib may be the treatment of choice over biologic DMARDs in patients (%agreement): refractory to ≥2 biologic DMARDs (100%), those in need of pain relief (85%), with intolerance to conventional DMARDs that would require monotherapy treatment (≥80%, except vs Anti-IL6), with advanced age (80%, except vs abatacept), with moderate-high levels of fatigue/ functional impairment (75%), with history of chronic or recurrent infections (≥75%, except vs abatacept), or with moderate-severe congestive heart failure (≥75%, except vs Anti-IL6/abatacept). Baricitinib may be the treatment of choice over other Janus kinase inhibitors in patients with: moderate liver failure (100%), advanced age (85%), or history of chronic/recurrent infections (75%).

Conclusions: There was consensus on the priority election of baricitinib over other drugs for RA treatment in a wide range of patient profiles, which may contribute to a better decision-making process and facilitate an individualized treatment selection.

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Expression of IL-33 and ST2 in peripheral blood mononuclear cells and serum of patients with active rheumatoid arthritis: A cross sectional study

Manju O Pai, S Venkatesh1, Praveen Kumar Singh2, Gaurav Badoni, Sarama Saha2, Pratima Gupta; Departments of Microbiology and 2Biochemistry, All India Institute of Medical Sciences, 1Department of General Medicine, Division of Rheumatology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Objective: There are a number of biochemical and inflammatory markers for rheumatoid arthritis (RA), a well-known autoimmune disease which attacks the joints, still there is a need to identify specific biomarkers that can be targeted for therapeutic purpose in these patients. This study attempted to study the levels of Interleukin 33 (IL-33) and its receptor ST2 in peripheral blood mononuclear cells (PBMC) and serum of active Rheumatoid Arthritis patients.

Methods: PBMC's and sera from 50 active RA patients and 50 healthy individuals were obtained. IL-33 and ST2 were measured using Real Time PCR with specific primers including internal controls using SyberGreen chemistry. Sandwich ELISA was done for protein expression studies for IL-33 and ST2.

Results: IL-33 and ST2 mRNA expression was significantly higher in patients with active RA, with estimated fold change of 3.533(ΔΔCt = -1.82121) and 4.172 (ΔΔCt = -2.15229) respectively, as compared to controls. Protein expression using sandwich ELISA revealed mean value of IL-33 to be significantly higher in RA patients than in controls (119.32±63.49 and 22.835±12.24 respectively). Similarly, an increase in serum protein of ST2 was also significantly higher in RA patients as compared to healthy controls (2434.328±834.60 and 705.22±310.05). Out of the total (nRA =50), 35 RA patients showed a hike in serum and mRNA expression of IL-33 which also showed correlation with other disease biomarkers like anti-CCP, CRP, DAS-28 CRP and HAQ-DI.

Conclusion: IL-33 and ST2 levels were elevated in both serum and PBMC's of RA patients and showed correlation with the disease activity. Therefore, IL-33/ST2L signalling represents to be involved in the pathogenesis of RA and also symbolizes to be a promising biomarker for RA that can be explored further for its therapeutic potential.

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Assessment of foot function and deformities in a cohort of patients with rheumatoid arthritis from Sri Lanka

Himantha Atukorale, H G H Udara, Dilusha Atukorale; Department of Rheumatology, District General Hospital, Matara, Sri Lanka

Background: Rheumatoid arthritis is known to cause deformities in the foot. Additionally, other foot defects could give rise to severe symptoms. These can impair foot functions and impact activities of daily living. Using footwear and appliances is considered beneficial to alleviate symptoms in patients with rheumatoid arthritis.

Objectives: The study aims to evaluate common foot deformities, functional impairment and symptoms in patients with established rheumatoid arthritis.

Methods: A sample of 72 patients treated for rheumatoid arthritis for over a year and who did not generally use footwear were recruited at Department of Rheumatology, Matara Hospital, Sri Lanka. Foot pain, assistive devices, surgeries, deformities, and Manchester Foot Pain and Disability Index (MFPDI) were studied using an interviewer-administered questionnaire [Table 1].

Figure 1: Reasons for avoiding footwear. Footwear was mostly avoided due to unawareness of its usefulness (54.2%), discomfort (18.1%), and slipperiness (16.7%)

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Table 1: The frequency and percentage of foot deformities in patients with rheumatoid arthritis

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Results: Majority (90.3%) were females. Mean (IQR) age was 60 (52-68)years. Mean duration of rheumatoid arthritis was 7.9 (SD- 6.44) years. Patients were on a mean number of 2 (SD-0.77) DMARDs. Mean BMI was 23.8kg/m2 (SD- 4.39). 25% and 37.5% was overweight and obese respectively. 52.8% had 1 or more comorbidities, the commonest being hypertension (20.4%). A majority of 68.1% reported foot pain, 41.7% had ankle pain, and 23.6% had forefoot pain. Only 2.8% have had foot surgeries. 12.5% were using assistive devices. Walking canes and modified shoes were used by 6.9%, and 5.6% respectively. 97.2% had one or more foot deformities.

Conclusions: Foot pain and deformities were frequently encountered among patients with rheumatoid arthritis necessitating proper evaluation of foot health. An awareness program is considered timely.

Duration of foot pain and number of DMARDs used positively correlated with MFPDI-pain intensity (p <0.05). Age of the patients positively correlated with MFPDI–personal appearance (p<0.05). The height of the patients negatively correlated with MFPDI-functional limitation (p<0.01). MFPDI-personal appearance positively correlated with functional limitation (p<0.05) and pain intensity (p<0.05).

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Evaluation of fracture risk by fracture risk assessment algorithm in patients of rheumatoid arthritis

Jainesh Jain, Rajnish Singh, Anil Taneja; ABVIMS and Dr. RML Hospital, New Delhi, India

Background: Rheumatoid Arthritis is a chronic autoimmune inflammatory disease with multisystemic, predominantly musculoskeletal involvement. RA patients are at high risk for osteoporosis and fractures. FRAX score is used to predict the 10 year risk of major osteoporotic and hip fracture.

Objectives: To assess bone mineral density (BMD) in patients with RA using DEXA scan (Dual Energy X-Ray absorptiometry) and calculate fracture risk using FRAX algorithm.

Methods: This cross sectional observational study conducted between 1 January 2021 and 31 May 2022 in tertiary care hospital in New Delhi enrolled 40 cases of RA. Demographic characteristics and anthropometric measurements were recorded, blood investigations including Rheumatoid factor (RF), Anti -citrullinated protein antibody (ACPA), erythrocyte sedimentation rate, C-reactive protein were done. DAS28-ESR was calculated. BMD was measured using DEXA scan and FRAX score was calculated using India specific FRAX calculator. Statistical analysis was done and p <0.05 was considered significant.

Results: Overall prevalence of osteoporosis was 55%. The mean of FRAX score for major osteoporotic fracture was 4.5 ± 5.18 % and for hip fracture was 2.11 ± 2.95%. Age, duration, swollen joint count, ESR, CRP, DAS28-ESR, and FRAX scores for major osteoporotic fractures and hip fractures were significantly higher in patients with osteoporosis. The independent predictors for higher FRAX scores are age, history of previous fracture, current smoker, history of glucocorticoid intake and T-score at femur neck [Table 1] and [Table 2].

Conclusions: Fracture risk using FRAX tool is higher in patients of Rheumatoid arthritis. There is high prevalence of osteoporosis in patients of RA. The independent predictors for higher FRAX scores are age, history of previous fracture, current smoker, history of glucocorticoid intake and T-score at femur neck.

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Prevalence and associations of extra-articular manifestations of rheumatoid arthritis: A cross-sectional study from a tertiary care center in South India

Harikrishnan Gangadharan, Akshay Akshay, Ronnie Thomas1, Josemon George; Departments of General Medicine and 1Community Medicine, Government Medical College, Kottayam, Kerala, India

Background: Extra-articular manifestations constitute a significant cause of morbidity and mortality in Rheumatoid arthritis (RA). There is a paucity of literature on the prevalence of extra-articular manifestations in South Indian patients with RA. We aimed to study the prevalence of extra-articular manifestations and their associations with various disease parameters in RA.

Methods: This was a hospital-based cross-sectional study conducted at a tertiary care teaching ho

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