Rheumatoid Arthritis Patients In Remission Research Articles

The relationship between disease activity with pan-immune-inflammatory value and systemic immune-inflammation index in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Immune system cells have an important role in RA. Our aim was to investigate the relationship between disease activity, systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) levels in RA patients. We planned to investigate whether these 2 measurements have an advantage over each other. About 67 patients diagnosed with RA and 49 healthy controls included in this study. RA was diagnosed based on 2010 ACR classification criteria. In this cross-sectional study, peripheral blood tests, C-reactive protein (CRP), hemogram, and erythrocyte sedimentation rate levels were noted after the physical examination of all participants. PIV was calculated with the formula: (neutrophil count × platelet count × monocyte count) / lymphocyte count. SII was calculated as follows: (neutrophil count × monocytes count) / lymphocyte count. The disease activity score 28 (DAS28) were noted in patients with RA. CRP values of active RA group were significantly higher than remission RA and control groups (P < .001), control and remission RA groups were similar (P = .86). PIV and SII are significantly higher in active RA than remission RA and control (P < .001, P < .001) higher in remission RA than control (P < .001, P < .001). Receiver operating characteristic curve analysis in predicting remission compared to the control group, CRP was not significant, PIV and SII was significant and PIV has higher sensitivity and sensitivity, a PIV value of > 217.31 have sensitivity 75.0% and specificity 85.7%. CRP, PIV, and SII are statistically significant in predicting active RA compared to the remission RA and control group. Our findings show that PIV, and SII are easy, inexpensive and reliable markers predicting remission in RA patients. CRP was not significant compared to remission RA and control group, PIV and SII was significant and PIV has higher sensitivity and specificity than SII in the remission group in RA. Patients with high disease activity, PIV, SII, and CRP levels were effective in showing disease activity compared to RA remission group and healthy controls.

A multiparametric risk table for loss of clinical remission status in patients with rheumatoid arthritis: A starter study post-hoc analysis.

This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis/arthritis Assessment in Rheumatoid Arthritis Patients in Remission (STARTER) study. Its primary aim was to determine the predictive clinical and MSUS features factors for disease flare in RA patients in clinical remission, whilst its secondary aim was to evaluate the probability of disease flare based on clinical and MSUS features. The analysis included a total of 389 RA patients in DAS28-defined remission. All patients underwent a MSUS examination according to OMERACT guidelines. Logistic regression and results presented as OR and 95%CI were used for the evaluation of the association between selected variables and disease flare. Significant clinical and MSUS features were incorporated into a risk table to predict disease flare within 12 months in RA remission patients. Within 12 months, 137(35%) RA patients experienced a disease flare. RA patients who experienced a flare disease differed from persistent remission for ACPA positivity (75.9%vs62.3%; p= 0.007), percentage of sustained clinical remission at baseline (44.1%vs68.5%; p= 0.001) and synovium PD signal presence (58.4%vs33.3%; p< 0.001). Based on these results, the three features were considered in a predictive model of disease flare with adjOR 3.064(95%CI 1.728-5.432). Finally, a risk table was constructed including the three significant predictive factors of disease flare within 12 months from the enrolment. An adaptive flare prediction model tool, based on data available in outpatient setting, were developed as a multiparametric risk table. If confirmed by the external validation, this tool might support the definition of therapeutic strategies in RA patients in DAS28-defined remission status.

The rs11568820 Variant in the Promoter Region of Vitamin D Receptor Gene Is Associated with Clinical Remission in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

The vitamin D receptor (VDR), binding to the active form of the vitamin, promotes the transcription of numerous genes involved in the proliferation of immune cells, cytokine production and lymphocyte activation. It is known that vitamin D deficiency can influence the risk of developing rheumatoid arthritis (RA) or modulate its disease activity. The aim of this study was to investigate a possible association between the rs11568820 (C > T) polymorphism in the promoter region of VDR gene and the response to therapy with anti-TNF drugs in patients with RA. A total of 178 consecutive Italian patients with RA treated with anti-TNF, naïve for biological therapy, were recruited. Disease activity data were evaluated using specific indices such as DAS28, CDAI and SDAI, measured at the start of therapy and subsequently at 22, 52, 104 and 240 weeks. A statistically significant association emerged between the rs11568820 variant allele of VDR gene and failure to remission assessed by CDAI and SDAI at 52 weeks, and by DAS28, CDAI and SDAI at 104 weeks of follow-up. Furthermore, the variant allele of this polymorphism was observed more frequently in patients who did not undergo sustained remission calculated by CDAI and SDAI. The variant T allele of rs11568820 in VDR gene is associated with a reduced remission rate with anti-TNFα drugs. These data suggest the role of VDR genetic variability in the response to therapy and in the achievement of remission.

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation

ObjectivesTo develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality...

Transsulfuration and folate pathways in rheumatoid arthritis: A systematic review and meta-analysis.

Metabolomic assessment of the transsulfuration and folic acid biochemical pathways could lead to the identification of promising biomarkers of nitric oxide dysregulation and oxidative stress in rheumatoid arthritis (RA). We conducted a systematic review and meta-analysis of transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6 , and vitamin B12 ) metabolites in RA patients in remission and healthy controls. Electronic databases were searched from inception to 15 July 2023 for relevant articles. We assessed the risk of bias using the JBI checklist and the certainty of evidence using GRADE. In 28 eligible studies, compared to controls, RA patients had significantly higher concentrations of homocysteine (standardized mean difference, SMD = 0.74, 95% CI 0.54-0.93, p < 0.001; low certainty of evidence) and methionine (SMD = 1.00, 95% CI 0.57-1.44, p < 0.001; low certainty) and lower concentrations of vitamin B6 (SMD = -6.62, 95% CI -9.65 to -3.60, p < 0.001; low certainty). By contrast, there were non-significant between-group differences in vitamin B12 and folic acid. In meta-regression and subgroup analysis, there were no associations between the effect size and several study and patient characteristics except for homocysteine (year of publication, C-reactive protein, triglycerides, and analytical method) and folic acid (biological matrix). The results of our study suggest that homocysteine, methionine, and vitamin B6 are promising biomarkers to assess nitric oxide dysregulation and oxidative stress in RA. (PROSPERO registration number: CRD42023461081).

Utility of sUPAR as a Novel Biomarker for Stratifying Rheumatoid Arthritis Patients in Remission

Introduction: Soluble urokinase plasminogen activator receptor (SuPAR) is a novel biomarker studied in conditions such as infections and malignancies. There is a paucity of data on suPAR levels in patients in RA clinical remission. A hypothesis-driven study was conducted to determine the level of suPAR, which will aid in the stratification of patients in remission. Methodology: This observational pilot study included 48 subjects (24 rheumatoid arthritis [RA] patients in clinical remission as per the American College of Rheumatology criteria and 24 age-matched healthy individuals). 28-Joint Disease Activity Score (DAS28) calculator was used to calculate disease activity. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma suPAR levels were assessed using suPARnostic® ELISA Assay kit (ViroGates, Denmark). The inflammatory parameters such as CRP, ESR, and suPAR were recorded at the time the patients were defined to be in clinical remission. Results: The median of suPAR level among cases in remission was 4.94 ng/mL and in controls was 3.54 ng/mL. The level of serum suPAR among RA remission patients was significantly higher (P &lt; 0.001) than in healthy individuals (P &lt; 0.001). The median of DAS28 score was 2.10, ESR 23, and CRP was 2.66. Nonparametric analysis (Spearman’s rho test) showed a significant correlation (P = 0.008) between DAS28 and ESR. The receiver operating characteristic showed area under the curve of 0.954 with sensitivity 83.3%, specificity 100%, negative predictive value 84%, and positive predictive value 100%. Conclusion: High suPAR levels among patients with clinical remission of RA demonstrate that these patients do possess baseline inflammatory status and hence continued treatment is required despite normal to mild range of ESR, CRP, and/or DAS 28 score. Thus, suPAR is a prognostic biomarker that can aid in better therapeutic management to patients with RA remission.

Administration of Liposomal-Based Pde3b Gene Therapy Protects Mice Against Collagen-Induced Rheumatoid Arthritis via Modulating Macrophage Polarization.

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterized by synovial inflammation and joint destruction. Despite progress in RA therapy, it remains difficult to achieve long-term remission in RA patients. Phosphodiesterase 3B (Pde3b) is a member of the phosphohydrolyase family that are involved in many signal transduction pathways. However, its role in RA is yet to be fully addressed. Studies were conducted in arthritic DBA/1 mice, a suitable mouse strain for collagen-induced rheumatoid arthritis (CIA), to dissect the role of Pde3b in RA pathogenesis. Next, RNAi-based therapy with Pde3b siRNA-loaded liposomes was assessed in a CIA model. To study the mechanism involved, we investigated the effect of Pde3b knockdown on macrophage polarization and related signaling pathway. We demonstrated that mice with CIA exhibited upregulated Pde3b expression in macrophages. Notably, intravenous administration of liposomes loaded with Pde3b siRNA promoted the macrophage anti-inflammatory program and alleviated CIA in mice, as indicated by the reduced inflammatory response, synoviocyte infiltration, and bone and cartilage erosion. Mechanistic study revealed that depletion of Pde3b increased cAMP levels, by which it enhanced PKA-CREB-C/EBPβ pathway to transcribe the expression of anti-inflammatory program-related genes. Our results support that Pde3b is involved in the pathogenesis of RA, and Pde3b siRNA-loaded liposomes might serve as a promising therapeutic approach against RA.

Ten-year radiographic and functional outcomes in rheumatoid arthritis patients in remission compared to patients in low disease activity

BackgroundTo compare the 10-year structural and functional prognosis between patients in sustained remission versus patients in sustained low disease activity (LDA) in early rheumatoid arthritis (RA).MethodsWe included 256 patients from the ESPOIR cohort who fulfilled the 2010 ACR/EULAR criteria for RA and who were in sustained remission using the Simple Disease Activity Index (SDAI) score (n = 48), in sustained LDA (n = 139) or in sustained moderate to high disease activity (MDA or HDA, n = 69) over 10 years. The mTSSs progression over 10 years and the 10-year HAQ-DI scores were compared between the 3 groups. A longitudinal latent process mixed model was used to assess the independent effect of SDAI status over time on 10-year mTSS progression and HAQ-DI at 10 years.ResultsPatients in sustained remission group were younger, had lower baseline HAQ-DI and mTSS scores and were less exposed to glucocorticoids, methotrexate or biologic disease-modifying anti-rheumatic drugs over 10 years. Patients in sustained remission had lower 10-year structural progression (variation of mTSS in the remission group: 4.06 (± 4.75) versus 14.59 (± 19.76) in the LDA group and 21.04 (± 24.08), p < 0.001 in the MDA or HDA groups) and lower 10-year HAQ-DI scores (10-year HAQ-DI in the remission group: 0.14 (± 0.33) versus 0.53 (± 0.49) in the LDA group and 1.20 (± 0.62) in the MDA or HDA groups, p < 0.001). The incidence of serious adverse events over 10 years was low, about 3.34/100 patient years, without any difference between the three groups.ConclusionRA patients in sustained SDAI remission have better long-term structural and functional outcomes in comparison to patients in sustained LDA.

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

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

Does manual lymphatic drainage improve upper extremity functionality in female patients diagnosed with rheumatoid arthritis? A randomized controlled study.

To demonstrate the effect of manual lymphatic drainage (MLD) on upper extremity functionality in patients with rheumatoid arthritis (RA). Thirty-nine female patients diagnosed with RA who were in remission were included in the study. The study group included 19 participants (mean age 50.63 ± 9.83 years), the control group included 20 participants (mean age 55.05 ± 5.89 years). The patients were randomized into two groups as home exercise program plus MLD and home exercise program alone. Both groups received treatment for 4 weeks. The primary outcome measure was pressure pain threshold (PPT). The patients were evaluated using the PPT, visual analog scale (VAS), hand-wrist joint range of motion examination, hand dynamometer and pinchmeter measurements, and the Rheumatoid Arthritis Quality of Life Scale before the interventention and at the end of the 4th week. The PPT evaluated at the thumbnail, wrist, and trapezius significantly increased in the study group after treatment (p < .001, p = .001, and p < .001, respectively). MLD was found to significantly increase the PPT at the thumbnail compared with home exercise program (p = .047). The VAS score significantly decreased in the study group (p = .011). The level of increase in radial deviation was statistically higher in the study group (p = .004). Manual lymphatic drainage had a positive effect on pain, PPT, and range of motion in RA patients in remission. MLD can be added to medical and other conservative treatments in RA patients.

Predictors of Remission in Rheumatoid Arthritis Patients Treated with Biologics:

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Association between SYVN1 and SEL1 genetic polymorphisms and remission in rheumatoid arthritis patients treated with TNF-α inhibitors: a machine learning approach.

Rheumatoid arthritis (RA) is a severe chronic inflammatory condition that affects joint synovium. Suppressor/enhancer of lin-12-like (SEL1L)-Synoviolin 1 (SYVN1)-mediated endoplasmic reticulum-associated degradation (ERAD) is highly associated with RA development. Although targeting SEL1L-SYVN1-mediated ERAD can be beneficial, studies that evaluate the association between polymorphisms in their genes and remission from the disease in RA patients taking tumor necrosis factor (TNF)-α inhibitors have yet to be carried out. Hence, the purpose of this study was to investigate the association between SYVN1 and SEL1L polymorphisms and TNF-α inhibitor response using various machine learning models. A total of 12 single-nucleotide polymorphisms (SNPs), including 5 SNPs in SYVN1 and 7 SNPs of SEL1L were investigated. Logistic regression analysis was used to examine the relationship between genetic polymorphisms and response to treatment. Various machine learning methods were employed to evaluate factors associated with remission in patients receiving TNF-α inhibitors. After adjusting for covariates, we found that sulfasalazine and rs2025214 in SEL1L increase the remission rates by approximately 3.3 and 2.8 times, respectively (95% confidence intervals 1.126-9.695 and 1.074-7.358, respectively). Machine learning approaches showed acceptable prediction estimates for remission in RA patients receiving TNF-α inhibitors, with the area under the receiver-operating curve (AUROC) values ranging from 0.60 to 0.65. A polymorphism of the SEL1L gene (rs2025214) and sulfasalazine were found to be associated with treatment response in RA patients receiving TNF-α inhibitors. These preliminary data could be used to tailor treatment for RA patients using TNF-α inhibitors.

IL-6 Signaling Attenuates TNF-α Production by Plasmacytoid Dendritic Cells in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is characterized by autoimmune joint destruction with debilitating consequences. Despite treatment advancements with biologic therapies, a significant proportion of RA patients show an inadequate clinical response, and restoration of immune self-tolerance represents an unmet therapeutic need. We have previously described a tolerogenic phenotype of plasmacytoid dendritic cells (pDCs) in RA patients responding to anti-TNF-α agents. However, the molecular mechanisms involved in tolerogenic reprogramming of pDCs in RA remain elusive. In this study, guided by transcriptomic analysis of CD303+CD123+ pDCs from RA patients in remission, we revealed enhanced expression of IL-6R and its downstream signaling compared with healthy pDCs. Functional assessment demonstrated that IL-6R engagement resulted in marked reduction of TNF-α secretion by pDCs whereas intracellular TNF-α was significantly increased. Accordingly, pharmacologic inhibition of IL-6R signaling restored TNF-α secretion levels by pDCs. Mechanistic analysis demonstrated impaired activity and decreased lysosomal degradation of ADAM17 (a disintegrin and metalloproteinase 17) sheddase in pDCs, which is essential for TNF-α cleavage. Importantly, reduction of TNF-α secretion by IL-6-treated pDCs attenuated the inflammatory potential of RA patient-derived synovial fibroblasts. Collectively, these findings position pDCs as an important source of TNF-α in RA pathogenesis and unravel an anti-inflammatory mechanism of IL-6 by limiting the pDC-derived TNF-α secretion.

Validity of Remission Criteria in Rheumatoid Arthritis Compared to Ultrasound-Defined Remission.

Remission is the ultimate purpose of treatment in rheumatoid arthritis (RA). However, even when the most stringent composite scores are used, structural damages can occur; hence, ultrasonography (US) appears to be the best way to assess real remission. This study aimed to investigate the validity of different RA remission scores using US as a reference. An analytic diagnostic study, of 30 RA patients in remission (according to the Disease Activity Score in 28 Joints [DAS28]) and a control group with active RA, was conducted between January and October 2018 at Mongi Slim Hospital in Tunis, Tunisia. Among them, patients in remission were identified according to their Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and the Boolean American College of Rheumatology/European League against Rheumatism activity index (ACR/EULAR) remission scores. The validity of each activity score for remission was calculated by considering the absence of power Doppler (PD) signals as a gold standard. All patients were in remission according to the DAS28, with an average score of 2.03 (1.1-2.6). US examination showed PD signals in 57% of patients. A total of 26 patients were in remission according to the CDAI; a Doppler signal was detected in 58% of those cases. SDAI remission was accomplished in 19 patients, with PD activity in 53% of cases. Of the 14 patients in remission according to the Boolean ACR/EULAR criteria, synovial hyper-vascularisation was found in 64%. Considering true remission as the absence of PD signals, the most sensitive and specific score was the DAS28 (93% and 68%, respectively). Considering remission in RA as the absence of vascularised synovitis, the DAS28 is the most sensitive and most specific score.

Does remission in rheumatoid arthritis bring kinesiophobia, quality of life, fatigue, and physical activity closer to normal?

This study aimed to compare kinesiophobia, fatigue, physical activity, and quality of life (QoL) between the patients with rheumatoid arthritis (RA) in remission and a healthy population. The prospective controlled study included 45 female patients (mean age: 54.22±8.2 year; range, 37 to 67 year) with a diagnosis of RA determined to be in remission according to the Disease Activity Score in 28 Joints (DAS28) being ≤2.6 between January 2022 and February 2022. As a control group, 45 female healthy volunteers (mean age: 52.2±8.2 year; range, 34 to 70 year) of similar age were evaluated. The QoL, disease activity, pain, kinesiophobia, fatigue severity, and physical activity were assessed using the Health Assessment Questionnaire, DAS28, Visual Analog Scale, Tampa Scale of Kinesiophobia, Fatigue Severity Scale, and International Physical Activity Questionnaire, respectively. There was no significant difference between the groups in demographic data. A statistically significant difference was found between the groups in terms of pain, C-reactive protein level, fatigue, kinesiophobia, QoL, and total, high, and moderate physical activity scores (p<0.001). Among the RA patients in remission, there was a significant correlation between kinesiophobia and moderate physical activity and QoL, as well as between fatigue and high physical activity (p<0.05). Patient education and multidisciplinary approach strategies should be developed to increase the QoL and physical activity and reduce kinesiophobia in RA patients in remission since there may be a decrease in physical activity due to kinesiophobia, fatigue, and fear of movement in this patient group compared to the healthy population, impairing their QoL.

Association of adiponectin levels with disease activity score, RA factor and ESR in rheumatoid arthritis patients

Introduction: Rheumatoid arthritis is a chronic inflammatory polyarthritis of relatively common occurrence affecting about 1-2% of adult population world-wide and 0.75% of Indian adults. The disease occurs at all ages and affects all ethnic groups. For early diagnosis and progression of rheumatoid arthritis might be useful for to better treatment of the patients. Present study aimed to assessment of adiponectin in newly diagnosed and remission rheumatoid arthritis patients. Materials and Methods: 100 Rheumatoid arthritis patients and 50 healthy volunteers with matching age, gender, and BMI were included in the study. All the subjects' biochemical, disease activity score, RA factor,ESR Rheumatoid Arthritis Patients and serum adiponectin levels were assessed. SPSS and Microsoft Excel Spreadsheets were used to conduct the necessary statistical analysis. Results: The patients with rheumatoid arthritis shown significantly higher levels of fasting blood sugar, postprandial blood sugars ,triglycerides , RA factor, ESR when compared to healthy controls (P=0.001**). Additionally we also discovered to be considerably significantly elevated levels of serum adiponectin (P= 0.001**). Furthermore there was very high significant positive correlation between serum adiponectin and disease activity score, RA factor, ESR.

Relationship between the prevalence of subclinical tenosynovitis and treatment in patients with RA in clinical remission: STARTER study.

This study is a sub-analysis from the patient cohort of the STARTER (Sonographic Tenosynovitis Assessment in RheumaToid arthritis patiEnts in Remission) study. The aim was to evaluate differences in ultrasound-detected joint and/or tendon involvement between patients receiving therapies based on a combination of conventional synthetic DMARDs (csDMARDs) and biologic DMARDs (bDMARDs) and those who were treated with either csDMARDs or bDMARDs in monotherapy. Four hundred and twenty-seven consecutive patients with a diagnosis of RA were recruited between October 2013 and June 2014. They were divided into three subgroups based on their therapy at baseline: patients with bDMARD in monotherapy, patients with csDMARD in monotherapy and patients in combination therapy (csDMARD + bDMARD). At baseline, 6 months and 12 months, a clinical examination (28 joint count) and an ultrasound evaluation were performed in each patient. A score of grey-scale (GS) and power Doppler (PD) synovitis and tenosynovitis was calculated based on the OMERACT scoring systems. Two hundred and fifty-six patients completed the observation period: 48 patients from the bDMARD group (18.75%), 152 patients from the csDMARD group (59.38%) and 56 patients from csDMARD + bDMARD group (21.88%). The analysis showed that GS tenosynovitis and PD tenosynovitis are better controlled in combination therapy than they are with csDMARD alone (P = 0.025 and P = 0.047, respectively); for PD synovitis, there was a better response in those who were treated with the combination therapy when compared with the patients receiving csDMARD (P = 0.01) or bDMARD (P = 0.02) alone. The analysis showed a lower prevalence of subclinical inflammatory manifestations detected with ultrasound imaging in those patients treated with the combination therapy than in those in monotherapy.

Sensory Neuron Expressed FcγRI Mediates Postinflammatory Arthritis Pain in Female Mice.

Persistent arthritis pain after resolution of joint inflammation represents a huge health burden in patients with rheumatoid arthritis (RA). However, the underling mechanisms are poorly understood. We and other groups recently revealed that FcγRI, a key immune receptor, is functionally expressed in joint nociceptors. Thus, we investigated a potential role of sensory neuron expressed FcγRI in postinflammatory arthritis pain in a mouse model of collagen antibody-induced arthritis (CAIA). Here, we show that global deletion of Fcgr1 significantly attenuated mechanical hyperalgesia in the ankle and hind paw of female mice in both inflammatory and postinflammatory phases of CAIA. No obvious differences in cartilage destruction were observed after resolution of joint inflammation between genotypes. In situ hybridization (ISH) revealed that a larger proportion of dorsal root ganglion (DRG) neurons expressed Fcgr1 mRNA signal in the late phase of CAIA. Conditional deletion of Fcgr1 in primary sensory neurons produced similar analgesic effects without affecting joint swelling. Knockdown of Fcgr1 expression within DRG in the postinflammatory phase of CAIA alleviated persistent pain. Inflammation within DRG after resolution of joint inflammation in the CAIA model was evidenced by T cell and neutrophil infiltration and upregulated mRNA expression of numerous inflammatory mediators. Yet, such changes were not altered by genetic deletion of Fcgr1. We suggest that neuroinflammation within the DRG after resolution of joint inflammation might upregulate FcγRI signaling in DRG neurons. Sensory neuron expressed FcγRI thus merits exploration as a potential target for the treatment of arthritis pain that persists in RA patients in remission.

Sensory testing and topical capsaicin can characterize patients with rheumatoid arthritis

Background and objectivesOur study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).MethodsWe used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)–based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]).ResultsThe application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max = − 0.65; RA patients: g*max = 0.72).ConclusionAs the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment.Key Points• The effect of topical capsaicin may represent the extent of TRPV1 sensitization in rheumatoid arthritis.• The effect of topical capsaicin on the amplitude level of CHEPs can unmask neuropathic symptoms.• The effect of topical capsaicin on CHEPs and HPTs can show the long-term consequences and the treatment success of RA patients in remission.

OA26 Erythrocyte mean corpuscular volume as a surrogate marker for methotrexate polyglutamation during early treatment in rheumatoid arthritis

Abstract Background/Aims The long-term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first-line disease-modifying therapy for the majority of patients. The gradual onset of action of methotrexate has been proposed to be linked to the build-up of intracellular stores of the drug, achieved through the process of polyglutamation. This is a complex and expensive assay. Recent work has shown an association between the increase in mean corpuscular volume (MCV) of erythrocytes and improvements in disease activity. This study seeks to relate intracellular methotrexate and 5-methyl-tetrahydrofolate polyglutamate concentrations with changes in MCV and their association with early ‘steroid free’ remission in RA patients. Methods 68 drug-naïve, newly diagnosed RA patients were recruited form the Newcastle Early Arthritis Clinic (NEAC). These patients were followed up for 6 months with serial blood sampling and quantification of the erythrocyte methotrexate and 5-methyl-tetrahydrofolate polyglutamate levels by liquid chromatography-mass spectrometry (LC-MS). This was then related to the contemporaneous erythrocyte MCV values from the clinical monitoring bloods on those occasions and the treatment outcome at 6 months. The outcome measure used was 4 component DAS28CRP remission (&amp;lt;2.4) with only the baseline intramuscular steroid permitted for the definition of remission. Results The majority of patients displayed a gradual increase in MCV over the first 6 months of treatment (MCV change from patient baseline used to normalise the data). When grouped by the ‘steroid free’ remission outcome, there was a divergence in MCV change with greater MCV increases observed in those achieving remission from 4 months of treatment onward (p &amp;lt; 0.05). In the same patient group, the accumulation of longer chain methotrexate polyglutamates (chain length 3 to 5) was observed to follow a similar trend to MCV with higher polyglutamate concentrations in those achieving the remission outcome from 2 months of treatment (P &amp;lt; 0.05). When the contemporaneous MCV and MTX polyglutamate samples were compared, an association was observed between the longer chain MTX polyglutamates and the change in MCV values (R2 = 0.39, p &amp;lt; 0.001), but not between intracellular 5-methyl-tetrahydrofolate and MCV (R2 = 0.01, p = NS). Conclusion Change in MCV shows an association with early remission induction with MTX therapy in treatment-naïve RA patients. This change in MCV appears to be associated with the accumulation of intracellular MTX metabolites, rather than via depletion of intracellular folates. MCV may therefore represent a tractable proxy measure of methotrexate polyglutamation for application in larger studies or for the purpose of drug monitoring. Disclosure P.M. Brown: None. A.G. Pratt: None. A.E. Anderson: None. A.W. Morgan: None. J.D. Isaacs: None.