Trajectories Of Disease Activity Research Articles

Optimized Treatment of Interleukin (IL-1)-Mediated Autoinflammatory Diseases: Impact of Disease Activity-Based Treatment Adjustments.

Background: Effective control of disease activity in Interleukin-1 autoinflammatory diseases (IL-1 AID) is crucial to prevent damage. The aim was to longitudinally analyze the impact of protocolized disease activity-based treatment adjustments in a real-life cohort. Methods: A single-center study of consecutive children with IL-1 AID followed between January 2016 and December 2019 was performed. Demographics, phenotypes, genotypes, inflammatory markers, physician (PGA), and patient/parent (PPGA) global assessment were captured. Disease activity and treatment changes were assessed. The impact of distinct parameters on disease activity trajectories was analyzed. Results: A total of 56 children were included, median follow-up was 2.1 years reflecting 361 visits. Familial Mediterranean Fever was the most common IL-1 AID. At the first visit, 68% of the patients had moderate/severe disease activity. Disease activity-based treatment adjustments were required in 28/56 children (50%). At last follow-up, 79% had a well-controlled disease. Both PGA and PPGA decreased significantly over time (p < 0.001; p < 0.017, respectively), however, both differed statistically at last visit (p < 0.001). Only PGA showed a significant estimated mean decrease across all IL-1 AID over time. Conclusions: Disease activity-based treatment adjustments can effectively refine treat-to-target strategies, enable personalized precision health approaches, and improve outcomes in children with IL-1 AID.

Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort

ObjectivesTo identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution...

Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

Distinct long-term disease activity trajectories differentiate early on treatment with etanercept in both rheumatoid arthritis and spondylarthritis patients: a prospective cohort study

To characterize disease activity trajectories and compare long-term drug retention between rheumatoid (RA) and spondylarthritis (SpA) patients initiating tumor necrosis factor inhibitor (TNFi) treatment (etanercept). Prospective observational study of RA, axial (AxSpA) and peripheral SpA (PerSpA) patients initiating etanercept during 2004–2020. Kaplan–Meier plots were used for drug retention comparisons and multivariable Cox regression models for predictors of discontinuation. Long-term disease activity trajectories were identified by latent class growth models using DAS28-ESR or ASDAS-CRP as outcome for RA and AxSpA respectively. We assessed 711 patients (450 RA, 178 AxSpA and 83 PerSpA) with a median (IQR) follow-up of 12 (5–32) months. At 5 years, 22%, 30% and 21% of RA, AxSpA and PerSpA patients, respectively, remained on therapy. Etanercept discontinuation was independent of the diagnosis and was predicted by gender and obesity in both RA and SpA groups. Four disease activity (DA) trajectories were identified from 6th month of treatment in both RA and AxSpA. RA patients in remission-low DA groups (33.7%) were younger, had shorter disease duration, fewer comorbidities and lower baseline disease activity compared to moderate (40.6%) & high DA (25.7%) groups. In AxSpA 74% were in inactive-low DA and they were more often males, non-obese and had lower number of comorbidities compared to higher ASDAS-CRP trajectories. In RA and AxSpA patients, disease activity trajectories revealed heterogeneity of TNFi treatment responses and prognosis. Male gender, lower baseline disease activity and fewer comorbidities, characterize a favourable outcome in terms of disease burden accrual and TNFi survival.

Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis

BackgroundMany patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA.MethodsWe studied patients from a validated electronic health record-based RA cohort with data from January 1, 2008, through July 31, 2019; all subjects prescribed ≥ 1 bDMARD or targeted synthetic (ts) DMARD were included. To determine whether subjects had similar b/tsDMARD sequences, the sequences were considered as a Markov chain over the state-space of 5 classes of b/tsDMARDs. The maximum likelihood estimator (MLE)-based approach was used to estimate the Markov chain parameters to determine the clusters. The EHR data of study subjects were further linked with a registry containing prospectively collected data for RA disease activity, i.e., clinical disease activity index (CDAI). As a proof of concept, we tested whether the clusters derived from b/tsDMARD sequences correlated with clinical measures, specifically differing trajectories of CDAI.ResultsWe studied 2172 RA subjects, mean age 52 years, RA duration 3.4 years, and 62% seropositive. We observed 550 unique b/tsDMARD sequences and identified 4 main clusters: (1) TNFi persisters (65.7%), (2) TNFi and abatacept therapy (8.0%), (3) on rituximab or multiple b/tsDMARDs (12.7%), (4) prescribed multiple therapies with tocilizumab predominant (13.6%). Compared to the other groups, TNFi persisters had the most favorable trajectory of CDAI over time.ConclusionWe observed that RA subjects can be clustered based on the sequence of b/tsDMARD prescriptions over time and that the clusters were correlated with differing trajectories of disease activity over time. This study highlights an alternative approach to consider subphenotyping of patients with RA for studies aimed at understanding treatment response.

Influence of Sex on Early Axial Spondyloarthritis: A Six-Year Longitudinal Analysis From a Large National Cohort.

The objective was to determine sex differences in disease outcomes in recent axial spondyloarthritis (SpA) over time. We analyzed the first 6 years of follow-up of the prospective French multicenter DESIR cohort. Patients analyzed had <3 years of disease, were naive to disease-modifying antirheumatic drugs, and fulfilled the Assessment of SpondyloArthritis international Society classification criteria for axial SpA. Disease activity (Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C-reactive protein [CRP] level), patient global assessment (PtGA), CRP level, and radiographic sacroiliitis were compared between men and women (self-reported sex) by linear and logistic mixed-effects models.Models were created for trajectories of disease activity over 6 years in men and women, using k-means. Of 494 patients analyzed (mean ± SD age 31.9 ± 7.5 years, symptoms duration 20.7 ± 11.7 months), 50.4% were men. Over 6 years of follow-up, both men and women showed clear improvements in ASDAS-CRP, PtGA, and CRP level. Women had higher ASDAS-CRP and PtGA over time compared to men (both P < 0.0001) with overall similar CRP levels (P=0.089), whereas structural damage increased more in men (P < 0.0001). One-third of both men (33%) and women (34%) belonged to persistent high/very high disease activity trajectories, but ASDAS-CRP was globally higher in women in these trajectories. In early axial SpA, clinical outcomes (disease activity and symptoms) were worse in women than men over 6 years of follow-up, whereas CRP was similar and structural damage was more frequent in men. Although similarly distributed, disease activity scores were higher in women in high/very high disease activity trajectories. Sex appears to be an important contextual factor in axial SpA.

Disease activity trajectories for early and established rheumatoid arthritis: Real-world data from a rheumatoid arthritis cohort.

Disease activity status described at fixed time points does not accurately reflect disease course in chronic and relapsing diseases such as rheumatoid arthritis (RA). We described longitudinal disease activity trajectories in early and established RA. Patients with available 28-Joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) over two years were included. Using latent growth curve modelling (LCGM), subgroups of patients following distinct patterns were identified. 1920 patients were included with 34.4% in early RA (< 2 years' disease duration). Three subgroups were identified using DAS28-ESR in early RA: 1) low disease activity to remission (LDA-REM: 19.1%); 2) moderate disease to remission (MD-REM: 54%); 3) high to moderate disease (HD-MD: 26.9%). The HD-MD group had a significantly higher number of comorbidities, biologic and steroid use and lower post-secondary education. Using CDAI, we identified seven subgroups with only 1.9% remission in early RA. In established RA, seven subgroups were identified using either DAS28-ESR or CDAI. Using DAS28-ESR 27.8% with HD showed improvement in disease status (14.2% HD-REM, 10.3% HD-LDA and 3.3% HD-MD) while using CDAI 17.9% showed improvement. Disease course was different in early and established RA. Only 14.2% of established RA reached DAS28-ESR remission compared to 73.1% of early RA. Using CDAI only 1.9% of early RA and none of the established RA achieved remission, likely reflecting the impact of the patient global assessment on this score. Findings also illustrate the impact of sociodemographic characteristics and early treatment on disease course.

Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry.

To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. Five trajectories of JIA disease activity, and associated baseline variables, were identified.

Distinct Long-Term Disease Activity Trajectories Differentiate Early on Treatment with Etanercept in Both Rheumatoid Arthritis and Spondylarthritis Patients

Distinct Long-Term Disease Activity Trajectories Differentiate Early on Treatment with Etanercept in Both Rheumatoid Arthritis and Spondylarthritis Patients

Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis.

To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revealed two trajectories of disease activity in each cluster: one with persistently high disease activity over time ('High'), the other rapidly evolving to low disease activity ('Low'). In cluster A patients, peripheral manifestations predisposed to the 'High' trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P= 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR)  = 2.1, 95% CI: 1.0, 4.4, P= 0.04 - Cox proportional-hazards model). Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.

Distinct patterns of disease activity over time in patients with active SLE revealed using latent class trajectory models

BackgroundSystemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune condition for which there are limited licensed therapies. Clinical trial design is challenging in SLE due at least in part to imperfect outcome measures. Improved understanding of how disease activity changes over time could inform future trial design. The aim of this study was to determine whether distinct trajectories of disease activity over time occur in patients with active SLE within a clinical trial setting and to identify factors associated with these trajectories.MethodsLatent class trajectory models were fitted to a clinical trial dataset of a monoclonal antibody targeting CD22 (Epratuzumab) in patients with active SLE using the numerical BILAG-2004 score (nBILAG). The baseline characteristics of patients in each class and changes in prednisolone over time were identified. Exploratory PK-PD modelling was used to examine cumulative drug exposure in relation to latent class membership.ResultsFive trajectories of disease activity were identified, with 3 principal classes: non-responders (NR), slow responders (SR) and rapid-responders (RR). In both the SR and RR groups, significant changes in disease activity were evident within the first 90 days of the trial. The SR and RR patients had significantly higher baseline disease activity, exposure to epratuzumab and activity in specific BILAG domains, whilst NR had lower steroid use at baseline and less change in steroid dose early in the trial.ConclusionsLongitudinal nBILAG scores reveal different trajectories of disease activity and may offer advantages over fixed endpoints. Corticosteroid use however remains an important confounder in lupus trials and can influence early response. Changes in disease activity and steroid dose early in the trial were associated with the overall disease activity trajectory, supporting the feasibility of performing adaptive trial designs in SLE.

Dual trajectories of fatigue and disease activity in an inception cohort of adults with systemic lupus erythematosus over 10 years.

Fatigue is one of the most common symptoms reported in patients living with SLE. We aim to: 1) determine if different trajectories of fatigue associate with specific latent classes of disease activity and 2) define the patient characteristics and associated factors in different latent classes. Data from an inception cohort of adult patients from the Toronto Lupus Clinic from 1997-2018 were analyzed. Fatigue levels were measured using Fatigue Severity Scale (FSS) and disease activity by the Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AMS). Dual latent class trajectory analysis, for fatigue and AMS, was performed. Univariable and multivariable logistic regression analyses assessed the association of baseline variables with class membership. Among 280 patients, 4 dual classes (C) of fatigue and disease activity were identified: C1- lowest disease activity and second highest fatigue trajectory (27%); C2- second highest disease activity and highest fatigue trajectory (30%); C3-moderate disease activity and lowest fatigue trajectory (33%); and C4- highest disease activity and moderate fatigue trajectory (10%). 4 distinct latent classes of dual fatigue and disease activity trajectories were identified. Fatigue and disease activity follow distinct trajectories and disease activity alone cannot fully explain fatigue trajectories. Trajectories with higher FSS scores were associated with more fibromyalgia and trajectories with higher disease activity were associated with higher cumulative glucocorticoid use. Higher baseline glucocorticoid use was more likely associated with more fatigue while older age at SLE diagnosis was associated with less fatigue.

Patient-reported wellbeing and clinical disease measures over time captured by multivariate trajectories of disease activity in individuals with juvenile idiopathic arthritis in the UK: a multicentre prospective longitudinal study.

SummaryBackgroundJuvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course.MethodsIn this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony.FindingBetween Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups.InterpretationAlmost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA.FundingMedical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.

P104 Longitudinal patient reported outcome data collected from a smartphone app can map group level trajectories of disease activity over time

Abstract Background Patient-reported outcome measures are a cornerstone of the current early inflammatory arthritis audit and part of the best practice tariff. However, outcome data are collected infrequently meaning longitudinal changes in disease activity cannot be accurately examined. We report results of a twelve-month clinical pilot of a cloud-enabled commercial smartphone app to record patient self-reported disease activity outcome measures to evaluate trends of disease activity in a routine rheumatology setting. Methods Patients with a clinical diagnosis of inflammatory arthritis attending routine rheumatology clinic were offered the opportunity to use a smartphone app to record their disease activity between hospital appointments using the RAPID3. Data from the first twelve months (July 2018 - July 2019) was extracted and latent class modelling using aggregate data was undertaken to explore the trends of disease activity experienced by our patients at a group level. Standard analysis recommendations were followed. Results Over the course of twelve-months, 58 patients used the app to record their disease activity using the RAPID3. These patients had a mean age of 53 and were 76% female. 35 patients had rheumatoid arthritis, 15 patients had psoriatic arthritis and 8 had another inflammatory arthritis. The median number of RAPID3 scores completed per patient was 8 (interquartile range 14), and a total of 706 RAPID3 scores were submitted over the 12 months. Three different trajectories of disease activity were identified among our cohort of patients. The first trajectory showed a low stable plateau of disease activity for six months before further improvement (27 patients:47%) over six months. The second trajectory (23 patients; 40%) showed an initial moderate disease activity which gradually declined over six months before improving markedly in the last three months, returning to moderate disease activity. The final trajectory (8 patients; 14%) identified patients with the highest disease activity which showed a gradual but slow improvement of disease activity over twelve months. These different trajectories show the changing burden of inflammatory arthritis over time. Conclusion Regular longitudinal data collection of patient-reported outcomes via a smartphone app can be used to show distinct group level trajectories of disease activity and could be used to examine changes in outcomes of patients over time. Data such as these could be used at a departmental level to examine the burden of inflammatory arthritis experienced by patients, assist planning future service requirements, and help anticipate the timings of future appointments more accurately for patients. Disclosures P.D.H. Hamann Consultancies; Living With Ltd. Royalties; PH has provided consultancy for and has an options and limited royalty agreement with, Living With Ltd. software company for the development of the smartphone application described in this abstract. N. Minaur None. J.H. Tobias None. E.M. Clark None.

Joint trajectories of disease activity, and physical and mental health-related quality of life in an inception lupus cohort.

To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership. In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership. Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes. High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.

Sociodemographic factors as determinants of disease, disability and quality of life trajectories in early rheumatoid arthritis: A multi-ethnic inception cohort study.

This study aims to describe the association between sociodemographic factors and trajectories of disease, disability and health-related quality of life (HRQoL) in early rheumatoid arthritis (ERA). Data were collected prospectively over 3years in the Singapore Early Arthritis Cohort study. Trajectories were modeled using multi-trajectory group-based trajectory modeling (GBTM) and determinants of trajectory membership were identified using multinomial logistic regression. Two hundred and thirteen patients were included: 58.2% Chinese, 16.4% Malay, 21.6% Indian, mean (SD) age 51.3 (12.6) years and symptom duration 21.8 (15.3) weeks. In the multi-trajectory analysis, three groups of disease trajectories and corresponding disability and HRQoL trajectories were identified: group 1 (moderate disease rapid response, 49.9%), group 2 (high disease rapid response, 31.1%) and group 3 (high disease slow response, 19.1%). Malay patients had higher relative risk ratio (RRR) of being in trajectory groups 2 and 3 compared to group 1 (RRR=2.30, 95% CI 1.05-3.98 and RRR=4.02, 95% CI 1.45-6.43, respectively) while patients with tertiary education had lower relative risk (RRR=0.56, 95% CI 0.45-0.89 and RRR=0.33, (95% CI 0.14-0.83, respectively). In the analysis of individual outcomes, ethnicity, education level and body mass index were determinants of the heterogeneous disease activity trajectories. Gender and education level were determinants of the disability trajectories. Only gender was a determinant of the HRQoL trajectories. Further, 96.2% of the patients were treated with conventional synthetic disease-modifying antirheumatic drugs. Disparities in sociodemographic factors should be taken into consideration in formulating treatment strategies in ERA.

Early response to anti-TNF predicts long-term outcomes including sustained remission: an analysis of the BSRBR-RA.

ObjectiveTo identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF.MethodsPatients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time.ResultsA total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into ‘modest’ (7986 patients; 55.3%) or ‘substantial’ (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted ‘maximal’ and ‘minimal’ response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving ‘maximal’ response between 2001–2008 and 2010–2013.ConclusionThis is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

Uncovering the heterogeneity of disease impact in axial spondyloarthritis: bivariate trajectories of disease activity and quality of life

ObjectiveThe goal of managing axial spondyloarthritis (axSpA) is to improve and maintain patients’ health-related quality of life (HRQoL), mainly through targeting towards low disease activity. Here, we aim to gain...

From Childhood to Adulthood: Disease Activity Trajectories in Childhood-Onset Systemic Lupus Erythematosus.

No previous study has studied the longitudinal disease course of childhood-onset systemic lupus erythematosus (cSLE). Our objectives are to assess distinguishable differences in disease activity trajectories in cSLE patients, determine baseline factors predictive of disease trajectory membership, and assess if the different disease activity trajectories are associated with different damage trajectories. This is a retrospective, longitudinal inception cohort of cSLE patients. Patients were followed from diagnosis as children, until they were adults. SLE disease activity was modeled as a latent characteristic, jointly using the Systemic Lupus Erythematosus Disease Activity Index 2000 and prednisone in a Bayesian growth mixture model. Baseline factors were tested for membership prediction of the latent classes of disease trajectories. Differences in damage trajectories by disease activity classes were tested using a mixed model. A total of 473 patients (82% females), with median age at diagnosis of 14.1 years, were studied. We studied 11,992 visits (2,666 patient-years). We identified 5 classes of disease activity trajectories. Baseline major organ involvement, number of American College of Rheumatology criteria, and age at diagnosis predicted memberships into different classes. A higher proportion of Asians was in class 2 compared to class 5. Class 1 was associated with the most accrual of damage, while class 5 was associated with no significant damage accrual, even after 10 years. There are 5 distinct latent classes of disease trajectory in patients with cSLE. Membership within disease trajectories is predicted by baseline clinical and demographic factors. Membership in different disease activity trajectory classes is associated with different damage trajectories.

Disease activity trajectories in early rheumatoid arthritis following intensive DMARD therapy over 3 years: association with persistence to therapy.

To identify the disease activity trajectories during intensive triple disease modifying anti-rheumatic drug (DMARD) therapy over 3 years in rheumatoid arthritis (RA) patients and to evaluate the association with treatment persistence. Disease Activity Score in 28 joints, baseline risk factors and medication usage were obtained from a longitudinal observational cohort of early RA patients, most of whom were treated with combination DMARD therapy consisting of methotrexate, sulfasalazine and hydroxychloroquine. Persistence of each DMARD was defined as the duration of time from initiation to cessation. A group-based trajectory modelling technique was used to identify disease activity trajectories. Three disease activity trajectories (good [43.8%], moderate [39.7%] and poor [16.5%]) were identified in a cohort of 297 patients. Most baseline risk factors, medication usage, the rate of treatment persistence and the effect of persistence on disease activity differed among patients in each of the three trajectories. Although the rate of persistence was higher in the trajectory with a good outcome, the association with persistence was more pronounced among patients who were in the poor outcome trajectory. Persistence with at least two or all three baseline DMARDs was associated with a decrease in disease activity to a broadly similar degree in all trajectories. After correction for other baseline prognostic factors, persistence with initial DMARDs contributes to heterogeneity in disease activity trajectory and there was an association between persistence with initial DMARD therapy and lower long-term disease activity.