scholarly journals Impact of Single-Nucleotide Polymorphisms of CTLA-4, CD80 and CD86 on the Effectiveness of Abatacept in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 10 (4) ◽  
pp. 220
Author(s):  
Noelia Marquez Pete ◽  
María del Mar Maldonado Montoro ◽  
Cristina Pérez Ramírez ◽  
Almudena Sánchez Martín ◽  
Juan Enrique Martínez de la Plata ◽  
...  

Abatacept (ABA) is used as a first-line treatment in patients diagnosed with moderate and severe rheumatoid arthritis (RA). The interindividual response to ABA therapy is very variable in these patients. The objective of our study was therefore to investigate the role of polymorphisms of the CTLA-4, CD80 and CD86 genes, as well as that of clinical factors of the disease, in the response to ABA in patients with RA. A retrospective cohort study was carried out in 109 patients receiving treatment with ABA and diagnosed with RA. The genetic variables were analyzed using real-time PCR with TaqMan® probes. The patients were classified according to the European League Against Rheumatism (EULAR) criteria at 6 and 12 months from start of treatment. The independent variables associated with higher EULAR response were lower duration of previous biologic disease-modifying anti-rheumatic drugs and lower baseline values of the disease activity score 28 after 6 months of ABA treatment; and lower baseline patient’s visual analogue scale (PVAS) after 12 months. In addition, a significant association was found between duration of ABA treatment, non-administration of concomitant glucocorticoids and lower baseline values of the number of inflamed joints and erythrocyte sedimentation rate clinical variables, with remission of the disease after 6 months’ treatment with ABA. Finally, remission of the disease after 12 months’ treatment with ABA was associated with earlier age at start of ABA therapy and lower number of previous biologic therapies (BTs). The CTLA-4rs5742909-T allele and the CTLA-4rs231775-G allele were found to be associated with satisfactory EULAR response and low disease activity (LDA) after 12 months’ treatment with ABA (CTLA-4rs5742909 T vs. CC; OR = 5.88; CI95% = 1.48–23.29 and OR = 4.75; CI95% = 1.35–17.94, respectively, and CTLA-4rs231775 G vs. AA, OR = 3.48; CI95% = 1.20–10.09 and OR = 4.68; CI95% = 1.49–17.94, respectively). In conclusion, patients with RA treated with ABA showed better EULAR response and LDA rate when they had the CTLA-4 rs5742909-T or CTLA-4 rs231775-G polymorphisms; furthermore, this remission rate increased in patients that began ABA treatment earlier, those with a lower number of previous BTs and those with a lower PVAS value.

2014 ◽  
Vol 41 (9) ◽  
pp. 1761-1765 ◽  
Author(s):  
Filip De Keyser ◽  
Ilse Hoffman ◽  
Patrick Durez ◽  
Marie-Joëlle Kaiser ◽  
Rene Westhovens ◽  
...  

Objective.Our study reports the results of the MIRA (MabThera In Rheumatoid Arthritis) registry, set up to collect data about clinical usage, patient profile, and retention of rituximab (RTX) treatment in daily clinical practice in Belgium.Methods.Patients with active rheumatoid arthritis (RA) who failed at least 1 anti-tumor necrosis factor (anti-TNF) treatment were included in our study between November 2006 and October 2011. At baseline, demographics, medication, disease history, disease activity, rheumatoid factor (RF), and anticyclic citrullinated peptide antibodies (anti-CCP) status were recorded. Evolution of the 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate, retreatments, and reasons for therapy stop were followed prospectively.Results.The MIRA registry included 649 patients, with mean disease duration of 12.8 ± 0.4 years and DAS28 values at inclusion of 5.85 ± 0.48. Patients received on average 2.82 ± 0.07 (range 1–9) RTX treatments, over a mean followup period of 93.1 ± 2.6 weeks. At database lock, 433 patients (66.7%) were still under RTX treatment, 182 (28.0%) had stopped treatment, and 34 (5.2%) were lost to followup. Ineffectiveness (n = 108, 59%) and safety concerns (n = 39, 22%) were the most frequent reasons for discontinuing RTX therapy. From 2006 to 2011, RTX practice patterns clearly evolved toward RTX being started in patients with a lower number of previously failed anti-TNF drugs and lower baseline DAS28 values. A lower number of previous anti-TNF drugs, and positivity for RF and anti-CCP, predicted more successful longterm treatment. RTX treatment provided adequate longterm disease control.Conclusion.In our daily practice study, RTX provided good longterm disease control and treatment retention in refractory patients with RA. Over the years, rheumatologists tended to start this treatment in patients with fewer previous anti-TNF treatments and lower disease activity.


2009 ◽  
Vol 69 (2) ◽  
pp. 420-423 ◽  
Author(s):  
Y A de Man ◽  
L E Bakker-Jonges ◽  
C M Dufour-van den Goorbergh ◽  
S P R Tillemans ◽  
H Hooijkaas ◽  
...  

Objectives:To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum.Methods:Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies.Results:The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups.Conclusions:Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1079.1-1079
Author(s):  
I. Yoshii

Background:Boolean remission criteria is one most popular and stringent criteria in treating patient with rheumatoid arthritis (RA), because it may guarantees a stable clinical course after attaining remission.Objectives:Impact of time span from initiation to achieving Boolean remission on maintaining disease activity, daily activities, and quality of life after attaining Boolean remission was investigated from daily clinical practice data.Methods:685 patients with RA since August 2010 under the T2T strategy were treated. They were monitored for their TJC, SJC, PGA, EGA, CRP, and disease activity indices such as CDAI, SDAI, DAS28, and Boolean criteria at every visit. HAQ-DI score, pain score using visual analog scale (PS-VAS), and EQ-5D were also monitored, and the quality of life score (QOLS) calculated from EQ-5D was determined at every visit from the time of diagnosis (baseline).Of 685 patients, 465 patients had achieved Boolean remission >1 times, and were consecutively followed up for >3 years. These patients were enrolled in the study. Time span from the first visit to first Boolean remission was calculated. The relationship between the time span and each of background parameters, and the relationship between the time span and each of the mean values of the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at the first Boolean remission and thereafter was evaluated statistically.Patients were subsequently divided into the G ≤ 6 and G > 6 groups based on the achievement of first Boolean remission within two groups: time span G ≤ 6 months and G > 6 months. The two groups were compared with regard to the SDAI score, HAQ score, PS-VAS, SHS, and QOLS at first visit and at the time of first Boolean remission, and the mean values of these parameters after remission were evaluated statistically. Moreover, changes of these parameters and the mean Boolean remission rate after the first remission, and SDAI remission rate at the first Boolean remission to thereafter were compared between the two groups statistically.Results:Out of 465 patients, females comprised 343 (73.7%), and the mean age was 67.8 years (range, from 21–95 years). The mean disease duration at first visit was 6.1 years (range, from 1 months–45 years). The mean follow up length was 88.1 months (range: 36–122 months; median: 85 months) and mean time span from the first visit to the first Boolean remission was 8.1 months. The mean SDAI score, HAQ score, PS-VAS, and the QOLS at first visit were 13.3, 0.467, 33.2, and 0.834, respectively. Among the study parameters, PS-VAS and QOLS were significantly correlated with the time span. For parameters at the first Boolean remission, HAQ-DI score, PS-VAS, and QOLS demonstrated significant correlation with the time span, whereas SDAI, HAQ-DI score, PS-VAS, SHS, and QOLS after the Boolean remission demonstrated significant correlation with the time span.The comparison between the G ≤ 6 and the G > 6 groups revealed that the disease duration, HAQ score, and PS-VAS at baseline in the G > 6 were significantly higher than that in the G ≤ 6 group, and QOLS in the G ≤ 6 group was significantly higher than that in the G > 6 group at baseline. Similarly, the HAQ score and PS-VAS at the first Boolean remission in the G > 6 group were significantly higher than that in the G ≤ 6 group, whereas QOLS in the G ≤ 6 group demonstrated no significant difference compared with that in the G > 6 group.The mean value of the SDAI score after the first Boolean remission in the G > 6 group was significantly higher than that in the G ≤ 6 group. Similarly, the SDAI score, HAQ score, and PS-VAS after the first Boolean remission in the G > 6 group were also significantly higher than those in the G ≤ 6 group, and the mean value of the QOLS in the G ≤ 6 group were significantly higher than that in the G > 6 group. The Boolean remission rate and SDAI remission rate after the first Boolean remission were significantly higher in the G ≤ 6 group than those in the G > 6 group.Conclusion:Attaining Boolean remission ≤ 6 months for RA has significant benefit for more stable disease control, that leads good maintenance of ADL.Disclosure of Interests:None declared


2015 ◽  
Vol 42 (7) ◽  
pp. 1090-1098 ◽  
Author(s):  
Leslie R. Harrold ◽  
George W. Reed ◽  
Ashwini Shewade ◽  
Robert Magner ◽  
Katherine C. Saunders ◽  
...  

Objective.To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis.Methods.Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models.Results.Patients (n = 265) were followed for 12 months with a mean change in CDAI of −8.1 (95% CI −9.8 – −6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of −10.1 (95% CI −13.2 – −7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of −10.5 (95% CI −12.9 – −8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22–0.73), which was robust to 4 different adjusted models (OR range 0.38–0.44).Conclusion.A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.


2020 ◽  
Author(s):  
Nga Thi Trinh ◽  
Hyun Jeong Kim ◽  
Woorim Kim ◽  
Sang Oh Kang ◽  
Kyung Hyun Min ◽  
...  

Abstract Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.


2017 ◽  
Vol 44 (6) ◽  
pp. 773-779 ◽  
Author(s):  
Julia Mary ◽  
Michel De Bandt ◽  
Cédric Lukas ◽  
Jacques Morel ◽  
Bernard Combe

Objective.For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure.Methods.We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ).Results.Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments.Conclusion.In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.


2011 ◽  
Vol 38 (12) ◽  
pp. 2509-2516 ◽  
Author(s):  
TED R. MIKULS ◽  
TRICIA D. LeVAN ◽  
HARLAN SAYLES ◽  
FANG YU ◽  
LIRON CAPLAN ◽  
...  

Objective.Soluble CD14 (sCD14) is involved in innate immune responses and has been implicated to play a pathogenic role in inflammatory diseases including rheumatoid arthritis (RA). No studies have identified the specific factors that influence sCD14 expression in RA. We used cross-sectional data to evaluate the relationship of sCD14 concentrations in RA with measures of disease activity and severity. We hypothesized that sCD14 concentrations would be elevated in subjects with greater RA disease severity and markers of disease activity, compared to subjects with lower disease activity. We also examined whether well-defined polymorphisms in CD14 are associated with sCD14 expression in RA.Methods.Soluble CD14 concentrations were measured using banked serum from patients with RA (n = 1270) and controls (n = 186). Associations of patient factors including demographics, measures of RA disease activity/severity, and select CD14 single-nucleotide polymorphisms (SNP) with sCD14 concentration were examined in patients with RA using ordinal logistic regression.Results.Circulating concentrations of sCD14 were higher in patients with RA compared to controls (p < 0.0001). Factors significantly and independently associated with higher sCD14 levels in patients with RA included older age, being white (vs African American), lower body mass index, elevated high sensitivity C-reactive protein, and higher levels of disease activity based on the Disease Activity Score (DAS28). There were no significant associations of CD14 tagging SNP with sCD14 level in either univariate or multivariable analyses.Conclusion.Circulating levels of sCD14 are increased in RA and are highest in patients with increased levels of RA disease activity. In the context of RA, sCD14 concentrations also appear to be strongly influenced by specific patient factors including older age and race but not by genetic variation in CD14.


2019 ◽  
Vol 56 (6) ◽  
pp. 703-708
Author(s):  
D. A. Kusevich ◽  
A. S. Avdeeva ◽  
V. V. Rybakova ◽  
N. V. Chichasova ◽  
E. L. Nasonov

Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment.Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®).Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI – 27.1 [23.0; 39.9], and CDAI – 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p<0.01). At week 12, the frequencies of ACR 20%, 50%, 70% improvements were 70, 55, and 5%; at week 24, these were 75, 45, and 15%, respectively. A good or moderate EULAR response at week 24 was observed in 25 and 60% of patients, respectively. At week 24, DAS28, SDAI, and CDAI remissions were achieved by 4 (20%), 2 (10%), and 1 (5%); low disease activity – by 4 (20%), 5 (25%), and 6 (30%) patients, respectively; high disease activity as measured by SDAI and CDAI remained in 3 (15%) patients. Two patients (10%) met the 2011 ACR/EULAR remission criteria at 24 weeks.Conclusion. The rituximab biosimilar Acellbia® 600 mg used in patients with active seropositive RA is clinically effective and comparable in the safety profile as shown in investigations of the brand-name MabThera® (F. Hoffman-La Roche Ltd., Switzerland) at a low dose (500 mg), as well as the first BA.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Sarah Wood ◽  
Kimme Hyrich ◽  
Suzanne Verstappen ◽  
Douglas Steinke

Abstract Background Until 2018, NICE guidance recommended the use of a combination of disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), in the initial management of people with rheumatoid arthritis (RA). In 2018 the guideline was updated to recommend monotherapy with MTX due to uncertainties in the evidence for combination therapy. However, it remains a requirement for progression onto any biologic that the patient should have persistent high disease activity and/or have intolerance to, a minimum of two DMARDs. The aim of this study was to understand the association between initial treatment strategy and EULAR response at 6 months. Methods This analysis included patients recruited to the longitudinal observational Rheumatoid Arthritis Medication Study (RAMS) in the UK who were DMARD naïve and had symptoms for less than 1 year. Patients were defined as either starting MTX monotherapy or MTX in combination with another DMARD (6 weeks either side of MTX start date) and categorised into EULAR non responders or moderate/ good responders after 6 months. A logistic regression model was applied to test the association between initial treatment strategy and EULAR response at 6 months, adjusting for confounders. Results A total of 948 participants were included in the analysis. MTX monotherapy was prescribed in 72% (n = 678) of patients and combination therapy was prescribed in 28% (n = 270) of patients, the majority of whom received MTX plus hydroxychloroquine (HCQ) (n = 236, 87%). There was no significant difference between the MTX monotherapy and combination therapy groups in EULAR response at 6-months (adjusted odds ratio [aOR] 0.77, 95% CI 0.53 to 1.14). Conclusion In this large UK observational study investigating the effect of treatment strategy within the first 6 weeks of presentation and treatment response at 6 months, there was no significant difference between combination DMARD therapy and MTX monotherapy on EULAR response. Most patients received MTX in combination with HCQ, for which little evidence exists. Disclosures S. Wood None. K. Hyrich Consultancies; ABBVIE. Grants/research support; BMS, PFIZER, UCB. S. Verstappen None. D. Steinke None.


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