scholarly journals Nerve size in chronic inflammatory demyelinating neuropathy varies with disease activity and therapy response over time: A retrospective ultrasound study

2014 ◽  
Vol 50 (5) ◽  
pp. 733-738 ◽  
Author(s):  
Craig M. Zaidman ◽  
Alan Pestronk
RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000721 ◽  
Author(s):  

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.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Liane D. Heale ◽  
Kristin M. Houghton ◽  
Elham Rezaei ◽  
Adam D. G. Baxter-Jones ◽  
Susan M. Tupper ◽  
...  

Abstract Background Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA). Methods In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach. Results in the JIA cohort were compared to normative Pediatric Bone Mineral Accrual Study data derived from healthy children using z-scores. Results At enrollment, PA z-score levels of study participants were lower than those in the normative population (median z-score − 0.356; p = 0.005). At enrollment, PA raw scores were negatively associated with the psychosocial domain of the Juvenile Arthritis Quality of Life Questionnaire (r = − 0.251; p = 0.023). There was a significant decline in PAQ-C/A raw scores from baseline (median and IQR: 2.6, 1.4–3.1) to 24 months (median and IQR: 2.1, 1.4–2.7; p = 0.003). The linear mixed-effect model showed that PAQ-C/A raw scores in children with JIA decreased as age, disease duration, and ESR increased. The PAQ-C/A raw scores of the participants was also negatively influenced by an increase in disease activity as measured by the JADAS-71 (p <  0.001). Conclusion Canadian children with newly diagnosed JIA have lower PA levels than healthy children. The decline in PA levels over time was associated with disease activity and higher disease-specific psychosocial stress.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 547.1-547
Author(s):  
C. Deakin ◽  
G. Littlejohn ◽  
H. Griffiths ◽  
T. Smith ◽  
C. Osullivan ◽  
...  

Background:The availability of biosimilars as non-proprietary versions of established biologic disease-modifying anti-rheumatic drugs (bDMARDs) is enabling greater access for patients with rheumatic diseases to effective medications at a lower cost. Since April 2017 both the originator and a biosimilar for etanercept (trade names Enbrel and Brenzys, respectively) have been available for use in Australia.Objectives:[1]To model effectiveness of etanercept originator or biosimilar in reducing Disease Activity Score 28-joint count C reactive protein (DAS28CRP) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with either drug as first-line bDMARD[2]To describe persistence on etanercept originator or biosimilar as first-line bDMARD in patients with RA, PsA or ASMethods:Clinical data were obtained from the Optimising Patient outcomes in Australian rheumatoLogy (OPAL) dataset, derived from electronic medical records. Eligible patients with RA, PsA or AS who initiated etanercept originator (n=856) or biosimilar (n=477) as first-line bDMARD between 1 April 2017 and 31 December 2020 were identified. Propensity score matching was performed to select patients on originator (n=230) or biosimilar (n=136) with similar characteristics in terms of diagnosis, disease duration, joint count, age, sex and concomitant medications. Data on clinical outcomes were recorded at 3 months after baseline, and then at 6-monthly intervals. Outcomes data that were missing at a recorded visit were imputed.Effectiveness of the originator, relative to the biosimilar, for reducing DAS28CRP over time was modelled in the matched population using linear mixed models with both random intercepts and slopes to allow for individual heterogeneity, and weighting of individuals by inverse probability of treatment weights to ensure comparability between treatment groups. Time was modelled as a combination of linear, quadratic and cubic continuous variables.Persistence on the originator or biosimilar was analysed using survival analysis (log-rank test).Results:Reduction in DAS28CRP was associated with both time and etanercept originator treatment (Table 1). The conditional R-squared for the model was 0.31. The average predicted DAS28CRP at baseline, 3 months, 6 months, 9 months and 12 months were 4.0 and 4.4, 3.1 and 3.4, 2.6 and 2.8, 2.3 and 2.6, and 2.2 and 2.4 for the originator and biosimilar, respectively, indicating a clinically meaningful effect of time for patients on either drug and an additional modest improvement for patients on the originator.Median time to 50% of patients stopping treatment was 25.5 months for the originator and 24.1 months for the biosimilar (p=0.53). An adverse event was the reason for discontinuing treatment in 33 patients (14.5%) on the originator and 18 patients (12.9%) on the biosimilar.Conclusion:Analysis using a large national real-world dataset showed treatment with either the etanercept originator or the biosimilar was associated with a reduction in DAS28CRP over time, with the originator being associated with a further modest reduction in DAS28CRP that was not clinically significant. Persistence on treatment was not different between the two drugs.Table 1.Respondent characteristics.Fixed EffectEstimate95% Confidence Intervalp-valueTime (linear)0.900.89, 0.911.5e-63Time (quadratic)1.011.00, 1.011.3e-33Time (cubic)1.001.00, 1.007.1e-23Originator0.910.86, 0.960.0013Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platform.Supported in part by a research grant from Investigator-Initiated Studies Program of Merck & Co Inc, Kenilworth, NJ, USA. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck & Co Inc, Kenilworth, NJ, USA.Disclosure of Interests:Claire Deakin: None declared, Geoff Littlejohn Consultant of: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus., Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Tegan Smith: None declared, Catherine OSullivan: None declared, Paul Bird Speakers bureau: Eli Lilly, abbvie, pfizer, BMS, UCB, Gilead, Novartis


2010 ◽  
Vol 38 (1) ◽  
pp. 60-63 ◽  
Author(s):  
DOMINIQUE IBAÑEZ ◽  
DAFNA D. GLADMAN ◽  
ZAHI TOUMA ◽  
MANDANA NIKPOUR ◽  
MURRAY B. UROWITZ

Objective.Adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS.Methods.Patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMSGOLD using all 12 visits), only quarterly visits (AMS3, using visits 3 months apart), semiannual visits (AMS6, using first, middle, and last visits only), and annual visits (AMS12, using only the first and last visits). Comparisons of AMS3, AMS6, and AMS12 with AMSGOLD are made using descriptive statistics.Results.Seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMSGOLD for the entire year was 2.05 (1.66), for AMS3 1.99 (1.65), for AMS6 2.12 (1.87), and for AMS12 2.08 (1.83). Mean (SD) of the absolute differences with AMSGOLD: for AMS3 0.29 (0.33), for AMS6 0.45 (0.59), and for AMS12 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMSGOLD to AMS3, 82% of the differences were minimal and 3% were important. When comparing to AMS6, 68% were minimal and 10% were important, while comparing to AMS12, 50% were minimal and 21% were important.Conclusion.Usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
S. Pazmino ◽  
A. Lovik ◽  
A. Boonen ◽  
D. De Cock ◽  
V. Stouten ◽  
...  

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


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 ◽  
...  

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.


Author(s):  
Alla Ishchenko ◽  
Johan Joly ◽  
Neerinckx Barbara ◽  
Rik Lories ◽  
Kurt de Vlam

Abstract Objectives Biological treatments revolutionized the management of psoriatic arthritis (PsA) by significantly improving clinical manifestations and preventing structural damage. Both result in better quality of life and improved physical functioning. Since the introduction of the first TNF inhibitor (TNFi) in the early 2000s, therapeutic options for PsA are increasing steadily and a new generation of biologicals, including anti interleukin (IL)-17 and anti IL23 strategies, allows distinct targeted approaches. The purpose of this study was to investigate whether the demographic, clinical and disease characteristics of PsA patients that are selected for first-line biological treatment, changed over time since the introduction of biologicals. Methods Patients with a clinical diagnosis of PsA were included in the KU Leuven BioSPAR registry, a prospective cohort of spondyloarthritis (SpA) and PsA patients treated with biologicals and targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs) such as apremilast and JAK inhibitors. Demographics, prior DMARD use, disease characteristics and disease activity parameters were recorded at the initiation of biological treatment and subsequently every 3-months for the first 2 years and later every 6 months. The patient data were compared in three treatment periods, corresponding with availability of the first and the second generation of TNF inhibitors and the third generation of biologicals. Results Analysis of 185 Caucasian patients with PsA from our prospective cohort showed longer disease duration and higher disease activity with higher tender joint count (TJC), swollen joint count (SJC) and higher CRP in the first as compared with the later time periods. The demographic characteristics and prior DMARD use did not change over time. Skin and nail psoriasis were more frequent in earlier compared with the later treatment periods. The bio-DMARD survival rate was similar in the early and later treatment periods. Conclusion The population of patients, selected for treatment escalation, changed over time since the introduction of biologicals. Our results suggest that with years of experience, PsA patients might be considered earlier and for therapy intensification in patients with less active disease as compared with profiles in the early days of biological treatment.


2021 ◽  
Author(s):  
Andrew Chen ◽  
Ronen Stein ◽  
Robert N. Baldassano ◽  
Jing Huang

ABSTRACTBackgroundThe current classification of pediatric CD is mainly based on cross-sectional data. The objective of this study is to identify subgroups of pediatric CD through trajectory cluster analysis of disease activity using data from electronic health records.MethodsWe conducted a retrospective study of pediatric CD patients who had been treated with infliximab. The evolution of disease over time was described using trajectory analysis of longitudinal data of C-Reactive Protein (CRP). Patterns of disease evolution were extracted through functional principal components analysis and subgroups were identified based on those patterns using the Gaussian mixture model. We compared patient characteristics, a biomarker for disease activity, received treatments, and long-term surgical outcomes across subgroups.ResultsWe identified four subgroups of pediatric CD patients with differential relapse-and-remission risk profiles. They had significantly different disease phenotype (p < 0.001), CRP (p < 0.001) and calprotectin (p = 0.037) at diagnosis, with increasing percentage of inflammatory phenotype and declining CRP and fecal calprotectin levels from Subgroup 1 through 4. The risk of colorectal surgery within 10 years after diagnosis was significantly different between groups (p < 0.001). We did not find statistical significance in gender or age at diagnosis across subgroups, but the BMI z-score was slightly smaller in subgroup 1 (p =0.055).ConclusionsReadily available longitudinal data from electronic health records can be leveraged to provide a deeper characterization of pediatric Crohn disease. The identified subgroups captured novel forms of variation in pediatric Crohn disease that were not explained by baseline measurements and treatment information.SummaryThe current classification of pediatric Crohn disease mainly relies on cross-sectional data, e.g., the Paris classification. However, the phenotypic classification may evolve over time after diagnosis. Our study utilized longitudinal measures from the electronic health records and stratified pediatric Crohn disease patients with differential relapse-and-remission risk profiles based on patterns of disease evolution. We found trajectories of well-maintained low disease activity were associated with less severe disease at baseline, early initiation of infliximab treatment, and lower risk of surgery within 10 years of diagnosis, but the difference was not fully explained by phenotype at diagnosis.


2007 ◽  
Vol 119 (1) ◽  
pp. S199
Author(s):  
J.A. Eckman ◽  
L.M. Gober ◽  
P.M. Sterba ◽  
R.G. Hamilton ◽  
S.S. Saini

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