scholarly journals SAT0021 STRUCTURAL EFFECTS OF LOCAL CRYOTHERAPY IN RHEUMATOID ARTHRITIS: A STUDY IN ADJUVANT-INDUCED ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 940.2-941
Author(s):  
C. Peyronnel ◽  
V. Petitcolin ◽  
P. Totoson ◽  
H. Martin ◽  
F. Verhoeven ◽  
...  

Background:The control of joint destruction caused by rheumatoid arthritis (RA) is a key issue in the treatment of this disease. Recent evidence showed that radiographic progression of joint damage occur despite a sharp decrease in disease activity and the use of aggressive Disease Modifying Anti-Rheumatic Drug (DMARD) therapies [1]. Whether alternative treatments such as cryotherapy may have beneficial effects on joint destruction at the early stages of the disease remains to be demonstrated, but such strategy would be of interest as it would not interfere with DMARDs treatment.Objectives:The aim of this study was to evaluate the effect of a 14-days-treatment of local cryotherapy on radiological outcomes in rat adjuvant induced arthritis.Methods:Adjuvant-induced arthritis (AIA) was induced in 6-weeks old male Lewis rats by injection ofMycobacterium butyricumin Freund’s incomplete adjuvant at the basis of the tail. A control group received saline. At the onset of arthritis, AIA rats were treated or not by application of cryotherapy on paws using either a cold spray or ice, twice a day for 14 days. Arthritis score and paws skin temperature was daily monitored. At the end of treatment, radiological exam of hind paws was performed and a score taking into account (swelling, osteoporosis, cartilage destruction, bone erosion, bone destruction and new bone formation) was assigned, according to Ackermanet al[2]. Circulating levels of cytokines (IL-6, IL-1β, TNF-α) was measured by Magpix Luminex kit.Results:Compared to untreated AIA, local cryotherapy significantly reduced the progression of arthritis score, whatever the modality (p<0.05), and to the same extent (reduction of arthritis score at day 24 post-immunization: -38% with cold spray, p<0.01, -37% with ice, p<0.01). Radiological score was significantly reduced by both treatments with no difference between the two treatments (-33% with cold spray, p<0.01, -44% with ice, p<0.01). All the items of the radiological score were equally reduced by ice and cold spray except swelling that was significantly reduced only by ice. Interestingly, the use of the cold spray induced a greater decrease in the skin temperature than the ice treatment (18.32 ± 0.07 °C vs 20.46 ± 0.08 °C, p<0.001). Conversely, cryotherapy did not significantly change the level of cytokines. No correlation was found between radiological score and arthritis score or cytokine levels.Conclusion:These data demonstrated that local cryotherapy had positive effects on structural damage in adjuvant-induced arthritis. The mechanisms involved remain now to be determined. These results suggest that local cryotherapy would be an interesting complement to conventional DMARDs in early RA.References:[1] Ten Klooster, P. M.et al.Radiographic progression can still occur in individual patients with low or moderate disease activity in the current treat-to-target paradigm: real-world data from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.Arthritis Res. Ther.21, 237 (2019).[2] Ackerman, N. R.et al.Effects of naproxen on connective tissue changes in the adjuvant arthritic rat.Arthritis Rheum.22, 1365–1374 (1979).Disclosure of Interests:Célian Peyronnel: None declared, Valentin Petitcolin: None declared, Perle Totoson: None declared, Hélène Martin: None declared, Frank Verhoeven: None declared, Céline Demougeot Grant/research support from: With an institutional support from Pfizer.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Daihei Kida ◽  
Nobunori Takahashi ◽  
Atsushi Kaneko ◽  
Yuji Hirano ◽  
Takayoshi Fujibayashi ◽  
...  

AbstractThis study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. ‘ACPA positive’ was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan–Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 477.2-477
Author(s):  
F. Hamdy ◽  
A. F. Enein ◽  
N. Morad ◽  
S. Tharwat ◽  
A. M. Abd el-Khalek ◽  
...  

Background:Rheumatoid arthritis (RA) is a systemic disease which results in chronic inflammation that primarily involves synovial joints resulting in progressive joint destruction [1]. Detection of subclinical disease activity is important as radiographic progression was observed during remission course in some cases [2]. Ultrasound can detect subclinical activity and synovial inflammation, which predict relapse and radiographic progression [3].Matrix Metaloprotinase 3 (MMP-3) is an enzyme, which is involved in joint destruction in RA patients. MMP-3 was found to correlate with disease activity, joint erosions, radiographic progression, drug responsiveness and disease outcome in patients with active RA [4]. However no data about its role in detection of subclinical activity in patients with clinical remission.Objectives:To assess the role of MMP-3 as a marker to discriminate subclinical activity from ultrasound remission in rheumatoid arthritis patients with remission.Methods:This study was conducted on 45 RA patients fulfilling remission or low disease activity criteria according to DAS 28 AND 45 healthy controls. Ultrasound evaluation was done for all patients using modified German US7 score. According to US7 score patients were classified into two groups: group with sonographic remission in which GS is 0±1 and the other group with subclinical disease activity with higher GS. Both groups underwent clinical and laboratory evaluation including MMP-3.Results:Sonographic remission was achieved in 44% of patients (20 patients). There was no statistically significant difference as regard age, gender, smoking, disease duration, morning stiffness duration, CDAI, treatment and laboratory data apart from hemoglobin level between patients with subclinical disease activity and patients with remission. However, there is statistically significant difference between the two groups as regard joint deformity, extra articular manifestations, DAS 28, SDAI and hemoglobin level.There was statistically significant difference in serum MMP-3 between RA patients and healthy control group. Serum MMP-3 was higher in RA patients with subclinical activity than patients with sonographic remission but the difference was not statistically significant (figure 1). Serum MMP-3 was positively correlated with ESR and synovitis score.Figure 1.Conclusion:Serum MMP-3 has correlation with US synovitis score. However, serum MMP-3 was not able to differentiate patients with sonographic remission from patients with subclinical disease activity. Ultrasound is still the gold standard for detection of subclinical disease activity.References:[1]Ergin, S. (2000). “Romatoid Artrit ve Sjögren Sendromu.” Fiziksel Tip ve Rehabilitasyon, Güneş Kitapevi: 1549-1576.[2]Ogishima, H., H. Tsuboi, N. Umeda, M. Horikoshi, Y. Kondo, M. Sugihara, T. Suzuki, I. Matsumoto and T. Sumida (2014). “Analysis of subclinical synovitis detected by ultrasonography and low-field magnetic resonance imaging in patients with rheumatoid arthritis.” Modern rheumatology24(1): 60-68.[3]Filippucci, E., E. Cipolletta, R. M. Mirza, M. Carotti, A. Giovagnoni, F. Salaffi, M. Tardella, A. Di Matteo and M. Di Carlo (2019). “Ultrasound imaging in rheumatoid arthritis.” La radiologia medica124(11): 1087-1100.[4]Lerner, A., S. Neidhöfer, S. Reuter and T. Matthias (2018). “MMP3 is a reliable marker for disease activity, radiological monitoring, disease outcome predictability, and therapeutic response in rheumatoid arthritis.” Best Practice & Research Clinical Rheumatology32(4): 550-562.Disclosure of Interests:None declared


2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared


2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 112.1-112
Author(s):  
L. Brandt ◽  
H. Schulze-Koops ◽  
T. Hügle ◽  
M. J. Nissen ◽  
H. Paul ◽  
...  

Background:The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are utilized to describe disease activity in RA patients. The DAS28 score can define states of low disease activity (LDA) and remission. Despite achieving LDA or remission, radiographic progression may nevertheless occur. However, the rates and frequency of this occurrence have not been analyzed in detail.Objectives:To describe the frequency and rate of radiographic progression in patients with persistent LDA or remission.Methods:Analysis of RA patients from the SCQM cohort. Persistent LDA or remission were defined as DAS 28 ≤3.2 or <2.6 respectively, at two subsequent follow up time points in the database. We included patients with at least two sets of radiographs within these intervals of LDA and/or remission. Radiographic progression was measured with the Ratingen-score (range 0-190), which describes joint erosions numerically. Repair was defined as an improvement in the Ratingen score >5 points/year and progression as >2 or >5 points change in the Ratingen score within one year.Results:Among 10’141 RA patients, 4’342 episodes of remission occurred in 3’927 patients with 1’776 sets of X rays available within these episodes. Similarly, 8’136 episodes of LDA in 6’765 patients and 2’358 sets of X rays were present within these intervals. For patients in LDA or remission, rates of repair were 5.5% and 4.8%, respectively, while for radiographic progression >5 points in the Ratingen score/year were 10.3% in both groups and for >2 points change of Ratingen score/year were 27.7 and 25.4%, respectively).No differences for demographic factors or measures of disease activity, rheumatoid factor or ACPA were found comparing patients with radiographic progression or non-progression despite LDA or remission at the beginning of the episode of LDA and/or remission.Interestingly, 42.9% of patients in LDA with progression of >5 points in the Ratingen score/year were current smokers vs 29.4% among the non-progressors (X2 = 6.55, p = 0.01). This significant difference vanished when the cut-off for radiographic progression was set at >2 points yearly change in Ratingen score or in patients in remission.Conclusion:Radiographic progression despite LDA or remission are more frequent than expected. No differences in radiographic progression were found comparing LDA and remission suggesting that the goal of LDA is appropriate. Smoking seems to be an independent risk factor for radiographic progression despite LDA. Why the effect of smoking could was not demonstrated in patients in remission, remains unclear.Disclosure of Interests:Lena Brandt: None declared, Hendrik Schulze-Koops: None declared, Thomas Hügle Consultant of: GSK, Abbvie, Pfizer, Jansen, Novartis, Eli Lilly., Michael J. Nissen Consultant of: Abbvie, Celgene, Eli-Lilly, Janssen, Novartis and Pfizer, Hasler paul Consultant of: Abbvie, Lilly, Rudiger Muller Consultant of: AbbVie, Novartis, Grant/research support from: Gebro


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 954.1-954
Author(s):  
M. Movahedi ◽  
D. Weber ◽  
P. Akhavan ◽  
E. Keystone

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease <3 years, were used. Only patients in the MTX arm were analyzed. RRP was defined as change in modified total Sharp (mTSS) > 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


2018 ◽  
Vol 71 (1) ◽  
pp. 43-49
Author(s):  
Christian A. Lechtenboehmer ◽  
Veronika K. Jaeger ◽  
Diego Kyburz ◽  
Ulrich A. Walker ◽  
Thomas Hügle

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