scholarly journals Novel methodology to discern predictors of remission and patterns of disease activity over time using rheumatoid arthritis clinical trials data

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000721 ◽  
Author(s):  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Disease Activity ◽  
Mixed Models ◽  
Latent Class ◽  
Activity Patterns ◽  
White Male ◽  
Therapy Response ◽  
Lower Baseline ◽  
Over Time

ObjectivesTo identify predictors of remission and disease activity patterns in patients with rheumatoid arthritis (RA) using individual participant data (IPD) from clinical trials.MethodsPhase II and III clinical trials completed between 2002 and 2012 were identified by systematic literature review and contact with UK market authorisation holders. Anonymised baseline and follow-up IPD from non-biological arms were amalgamated. Multiple imputation was used to handle missing outcome and covariate information. Random effects logistic regression was used to identify predictors of remission, measured by the Disease Activity Score 28 (DAS28) at 6 months. Novel latent class mixed models characterised DAS28 over time.ResultsIPD of 3290 participants from 18 trials were included. Of these participants, 92% received methotrexate (MTX). Remission rates were estimated at 8.4%(95%CI 7.4%to9.5%) overall, 17%(95%CI 14.8%to19.4%) for MTX-naïve patients with early RA and 3.2% (95% CI 2.4% to 4.3%) for those with prior MTX exposure at entry. In prior MTX-exposed patients, lower baseline DAS28 and MTX reinitiation were associated with remission. In MTX-naïve patients, being young, white, male, with better functional and mental health, lower baseline DAS28 and receiving concomitant glucocorticoids were associated with remission. Three DAS28 trajectory subpopulations were identified in MTX-naïve and MTX-exposed patients. A number of variables were associated with subpopulation membership and DAS28 levels within subpopulations.Conclusions Predictors of remission differed between MTX-naïve and prior MTX-exposed patients at entry. Latent class mixed models supported differential non-biological therapy response, with three distinct trajectories observed in both MTX-naïve and MTX-exposed patients. Findings should be useful when designing future RA trials and interpreting results of biomarker studies.

scholarly journals Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110439
Author(s):  
◽  
Michael Barnes ◽  
Sarah Brockbank ◽  
Ian N Bruce ◽  
Coziana Ciurtin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Alcohol Intake ◽  
Latent Class ◽  
Short Form ◽  
Well Being ◽  
Disease Course ◽  
Clinical Predictors ◽  
Seropositive Rheumatoid Arthritis ◽  
Lower Baseline

Background: To characterise disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment-naïve patients with seropositive rheumatoid arthritis (RA). Methods: Patients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterised disease course. Results: We enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline Health Assessment Questionnaire (HAQ) and SDAI predicted 6-month remission ( p = 0.013 and 0.011). Alcohol intake and baseline prescribing of methotrexate with a second disease-modifying antirheumatic drug (DMARD; vs monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%). Baseline HAQ and Short Form-36 Health Survey – Mental Component Score (SF-36 MCS) distinguished these groups. In addition, a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations. Conclusion: Three distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. We hypothesise that biological markers collected early in disease course (within 6 months) may help patient management and better targeting of existing and novel therapies.

scholarly journals SAT0192 TRAJECTORIES OF LUPUS DISEASE ACTIVITY OVER TIME IN THE CLINICAL TRIAL SETTING REVEALED BY LATENT CLASS MIXED MODELS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1038.1-1038
Author(s):  
J. Reynolds ◽  
J. Prattley ◽  
M. Lunt ◽  
N. Geifman ◽  
I. N. Bruce
Keyword(s):  
Clinical Trial ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mixed Models ◽  
Latent Class ◽  
Active Drug ◽  
Drop Out ◽  
Steroid Dose ◽  
Predictors Of Response ◽  
Over Time

Background:There is considerable debate regarding the most appropriate outcome measures for clinical trials in systemic lupus erythematosus (SLE). We propose that studying changes in disease activity over time may yield important information above and beyond fixed endpoints at 12 months.Objectives:To compare outcomes and predictors of response using i) traditional response definitions at a fixed time point and ii) trajectories of disease activity over time in a clinical trial dataset.Methods:Data from the phase 3 clinical trial of Epratuzumab (EMBODY) in patients with active SLE were reanalysed. Response at 12 months was defined as: reduction to ≤1 BILAG B score, no increase in SLEDAI-2K score and no increase in prednisolone dose. Latent class mixed models (LCMM) were constructed using the numerical BILAG-2004 (nBILAG) score (where A=12, B=8, C=1, D/E=0) from the screening visit until trial end. Cumulative prednisolone and Epratuzumab exposure was determined by estimating the area under the dose-time or concentration-time curves (AUC) respectively.Results:1202 patients were included with a median disease duration of 5.6 [1.9, 12.7] years and baseline nBILAG score of 20 [16, 24]. At 12 months there were 564/1202 (46.9%) responders. There was no association between receiving Epratuzumab and response. Responders were older, with lower baseline nBILAG score and baseline steroid dose. Using a cubic spline LCMM in the whole cohort, 5 trajectories were identified: Non-responders (NR, 33.9%), rapid responders (RR, 36.7%), slow responders (SR, 20.7%), flare (F, 4.7%) and high disease activity (HDA, 3.9%) (figure). Of the 564 12-month responders, 113 (20.4%) were in the NR latent class whilst 417 (73.9%) were in RR or SR classes. Whilst there were no differences in study drop-out due to adverse events, withdrawal due to inefficacy was 20.6% in NR compared to 8.4% in RR and 7.6% in SR.In multivariable logistic regression models adjusted for age, gender and study drop-out, being a responder (RR or SR) was significantly associated with activity in constitutional, musculoskeletal and cardiorespiratory BILAG domains, higher baseline and cumulative steroid exposure, and receiving active drug.There was a trend towards higher baseline CD19+ counts in RR compared to NR or SR (p=0.108) but in a population-averaged multivariable linear model only baseline CD19+ count, Epratuzumab and steroid dose were associated with number of CD19+ cell over time (p<0.001 for each).Conclusion:Compared to a fixed end-point at 12 months, LCMM identified trajectories of disease activity and an association between clinical improvement and receiving active drug. Predictors of response vary significantly according to the response definition used.Table.Comparison of predictors of response between the 2 modelsResponse at 12 monthsResponse latent call (RR or SR)AgeYesNoBaseline gBILAG scoreYes (negative)Yes (positive)Baseline steroid doseYesYesActive diseaseConstitutionalNoYesMusculoskeletalNoYesCardiorespiratoryNoYesGastroenterologicalYesNoAnti-SmithYesNoLow C3YesNoEpratuzumabNoYesAcknowledgments:Presented on behalf of the MASTERPLANS ConsortiumDisclosure of Interests:John Reynolds: None declared, Jennifer Prattley: None declared, Mark Lunt: None declared, Nophar Geifman: None declared, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB

scholarly journals Characterization of disease course and remission in early seropositive rheumatoid arthritis: Results from the TACERA longitudinal cohort study

2020 ◽  
Author(s):  
◽  
Brian Tom
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Alcohol Intake ◽  
Latent Class ◽  
Well Being ◽  
Disease Course ◽  
Clinical Predictors ◽  
Seropositive Rheumatoid Arthritis ◽  
Baseline Activity ◽  
Lower Baseline

ABSTRACTBackgroundTo characterize disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment naïve patients with seropositive rheumatoid arthritis (RA).MethodsPatients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using DAS28-CRP and SDAI. Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterized disease course.ResultsWe enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline HAQ and SDAI predicted 6-month remission (p=0.002 and 0.021). Alcohol intake and baseline prescribing of methotrexate with a second DMARD (versus monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an Inadequate Responder group (6.5%), and Higher and Lower Baseline Activity Responder groups (22.4% and 71.1%). Baseline HAQ and SF-36 MCS only distinguished these groups. Additionally a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations.ConclusionsThree distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. Biological markers collected early in disease course (within 6 months) may help patient management and to better target existing and novel therapies.

scholarly journals FRI0020 CLINICAL TREATMENT RESPONSE STILL DOES NOT MATCH PATIENT REPORTED IMPROVEMENT, EVEN IN EARLY RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
S. Pazmino ◽  
A. Lovik ◽  
A. Boonen ◽  
D. De Cock ◽  
V. Stouten ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Health Assessment ◽  
Sustained Remission ◽  
Research Support ◽  
Early Ra ◽  
Severity Scores ◽  
Patient Reported ◽  
Over Time

Background:Commonly used disease activity scores in rheumatoid arthritis (RA) include one patient reported outcome (PRO) -the patient’s global health assessment (PGA). Exploratory factor analysis (EFA) was performed on data from the 2 year Care in early Rheumatoid Arthritis (CareRA) trial to explain the evolution of disease burden extracting 3 factors.1Objectives:To assess the evolution and relative responsiveness over time of clinical, laboratory and patient assessments included in composite scores, together with other PROs like pain, fatigue and functionality in patients with early RA (≤1 year) treated to target (T2T) within the CareRA trial.Methods:DMARD naïve patients with early RA (n=379) were included, randomized to remission induction with COBRA-like treatment schemes (n=332) or MTX monotherapy (n=47) and T2T.Components of disease activity scores (swollen/tender joint count (S/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), and physician (PhGH) or patient (PGA) global health assessment), pain and fatigue (both on 0-100 scale) and HAQ were recorded at every visit.Missing data was handled with multiple imputation (n=15). Clustering was removed with multiple outputation (n=1000), then each of the 15 000 datasets was analyzed by EFA with principal component extraction and oblimin rotation. The analyses were combined after re-ordering the factors by maximizing factor congruence. The 3 extracted factors and their individual components (with their loadings) were: 1. Patient containing PGA (0.87), pain (0.86), fatigue (0.90) and HAQ (0.5) 2.Clinical with SJC (0.92), TJC (0.89) and PhGH (0.76) and 3.Laboratory with CRP(0.87) and ESR (0.78).1(Pazmino, ACR 2019 abstract, Table 3)Afterwards, variables were first normalized to a 0-1 scale, then multiplied -weighted- by the factor loadings previously obtained.1For each Patient, Clinical and Laboratory severity score, the weighted variables belonging to each score were summed together and then re-scaled to 0-1 (higher values suggest more burden).The percentage (%) improvement from baseline to week 104 and the area under the curve (AUC) across time points were calculated per factor.Differences in % improvement and AUC were compared between patients not achieving and achieving early and sustained (week 16 to 104) disease activity score remission (DAS28CRP <2.6) with ANOVA. Bonferroni correction was used for multiple testing.Results:Severity scores of Patient, Clinical and Laboratory factors improved rapidly over time (Figure 1). In patients achieving sustained remission (n=122), Patient, Clinical and Laboratory scores improved 56%, 90% and 27% respectively. In patients not achieving sustained remission (n=257) the improvement was 32%, 78% and 9% respectively (p<0.001 only for clinical improvement).Patients in CareRA who achieved sustained remission had an AUC of 15.1, 3.4 and 4.7 in Patient, Clinical and Laboratory scores respectively, compared to 32.3, 10.0, and 7.2 in participants not achieving sustained remission (p<0.001 for all comparisons).Conclusion:Patient, Clinical and Laboratory severity scores improved rapidly over time in patients achieving rapid and sustained disease control. However, overall, Patient burden seemed not to improve to the same extent as Clinical burden. Patient’s unmet needs in terms of pain, fatigue, functionality and overall well-being should thus be given more attention, even in patients in sustained remission.References:[1]Pazmino S,et al.Including Pain, Fatigue and Functionality Regularly in the Assessment of Patients with Early Rheumatoid Arthritis Separately Adds to the Evaluation of Disease Status [abstract]. ACR. 2019.Disclosure of Interests:Sofia Pazmino: None declared, Anikó Lovik: None declared, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department), Diederik De Cock: None declared, Veerle Stouten: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

scholarly journals Effectiveness of Rituximab for the Treatment of Rheumatoid Arthritis in Patients with Prior Exposure to Anti-TNF: Results from the CORRONA Registry

2015 ◽  
Vol 42 (7) ◽  
pp. 1090-1098 ◽  
Author(s):  
Leslie R. Harrold ◽  
George W. Reed ◽  
Ashwini Shewade ◽  
Robert Magner ◽  
Katherine C. Saunders ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Effectiveness ◽  
High Disease Activity ◽  
Low Disease Activity ◽  
Logistic Regression Models ◽  
Lower Baseline ◽  
Previously Treated

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.

scholarly journals Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.

2011 ◽  
Vol 38 (10) ◽  
pp. 2095-2104 ◽  
Author(s):  
JACOB KARSH ◽  
EDWARD C. KEYSTONE ◽  
BOULOS HARAOUI ◽  
J. CARTER THORNE ◽  
JANET E. POPE ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Disease Activity ◽  
Study Design ◽  
New Drugs ◽  
Nominal Group ◽  
Consensus Method ◽  
Inclusion Criteria ◽  
Design Features

Objective.Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.Methods.Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.Results.Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.Conclusion.There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals Stability of ARDS subphenotypes over time in two randomised controlled trials

Thorax ◽  
2018 ◽  
Vol 73 (5) ◽  
pp. 439-445 ◽  
Author(s):  
Kevin Delucchi ◽  
Katie R Famous ◽  
Lorraine B Ware ◽  
Polly E Parsons ◽  
B Taylor Thompson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Randomised Controlled Trials ◽  
Latent Class ◽  
Lung Protective Ventilation ◽  
Controlled Trials ◽  
Transition Analysis ◽  
Class 1 ◽  
Randomised Controlled ◽  
Over Time

RationaleTwo distinct acute respiratory distress syndrome (ARDS) subphenotypes have been identified using data obtained at time of enrolment in clinical trials; it remains unknown if these subphenotypes are durable over time.ObjectiveTo determine the stability of ARDS subphenotypes over time.MethodsSecondary analysis of data from two randomised controlled trials in ARDS, the ARMA trial of lung protective ventilation (n=473; patients randomised to low tidal volumes only) and the ALVEOLI trial of low versus high positive end-expiratory pressure (n=549). Latent class analysis (LCA) and latent transition analysis (LTA) were applied to data from day 0 and day 3, independent of clinical outcomes.Measurements and main resultsIn ALVEOLI, LCA indicated strong evidence of two ARDS latent classes at days 0 and 3; in ARMA, evidence of two classes was stronger at day 0 than at day 3. The clinical and biological features of these two classes were similar to those in our prior work and were largely stable over time, though class 2 demonstrated evidence of progressive organ failures by day 3, compared with class 1. In both LCA and LTA models, the majority of patients (>94%) stayed in the same class from day 0 to day 3. Clinical outcomes were statistically significantly worse in class 2 than class 1 and were more strongly associated with day 3 class assignment.ConclusionsARDS subphenotypes are largely stable over the first 3 days of enrolment in two ARDS Network trials, suggesting that subphenotype identification may be feasible in the context of clinical trials.

scholarly journals The Relation Between Disease Activity, Patient‐Reported Outcomes, and Grip Force Over Time in Early Rheumatoid Arthritis

2019 ◽  
Vol 1 (8) ◽  
pp. 507-515
Author(s):  
Maria Rydholm ◽  
Ingegerd Wikström ◽  
Sofia Hagel ◽  
Lennart T. H. Jacobsson ◽  
Carl Turesson
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Patient Reported Outcomes ◽  
Grip Force ◽  
Patient Reported ◽  
Over Time

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 ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Remission Rate ◽  
Lower Number ◽  
Nucleotide Polymorphisms ◽  
Eular Response ◽  
European League Against Rheumatism ◽  
Lower Baseline ◽  
Aba Therapy ◽  
Baseline Values

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.

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