Correction: Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.
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ABSTRACT:
SUBMITTER: Pan Y
PROVIDER: S-EPMC7117688 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Correction: Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.
Pan Yi Y Norton Sam S Gwinnutt James M JM Kearsley-Fleet Lianne L Symmons Deborah P M DPM Lunt Mark M Young Adam A Hyrich Kimme L KL Verstappen Suzanne M M SMM
PloS one 20200402 4
[This corrects the article DOI: 10.1371/journal.pone.0215999.]. ...[more]
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Project description:BackgroundUnited Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA.MethodsThe study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register-RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership.ResultsIn total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.ConclusionThere is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.
| S-EPMC6527224 | biostudies-literature
Project description:Background:Many patients with rheumatoid arthritis (RA) do not attain remission/low disease activity, remaining in a moderate disease activity state (MDAS) with ongoing disability and impaired quality of life (QoL). If patients in persistent MDAS with poor future outcomes could be prospectively identified, they could arguably be treated more intensively. We evaluated baseline factors predicting function (Health Assessment Questionnaire-Disability Index [HAQ-DI] scores) and QoL (3-level EuroQol-5 dimensions questionnaire [EQ-5D-3L] index scores) at 12?months in patients with RA in persistent MDAS in a real-world setting. Methods:Patients with persistent MDAS (Disease Activity Score for 28-joint count based on erythrocyte sedimentation rate [DAS28-ESR] 3.2-5.1 on at least two consecutive outpatient appointments over 12?months) were identified retrospectively from Guy's Hospital RA Centre and analysed in two groups: (1) biologic naïve at baseline or (2) receiving/ever received biologics. The baseline timepoint was the second-visit MDAS DAS28-ESR score; the endpoint was the closest visit to 12?months. Linear regression analyses evaluated relationships between baseline variables and (1) 12-month HAQ-DI scores, (2) 12-month rank-transformed EQ-5D-3L index scores, (3) 12-month changes in HAQ-DI scores, and (4) 12-month changes in EQ-5D-3L index scores. Results:The analysis included 207 biologic-naïve and 188 biologic-experienced patients. All patients had moderate disability (mean HAQ-DI 1.21 and 1.46) and impaired QoL (mean EQ-5D-3L index scores 0.52 and 0.50). Many reported moderate/severe pain (93 and 96%) and showed little change in HAQ-DI and EQ-5D-3L index scores over 12?months. In both biologic-naïve and biologic-experienced groups, multivariate analysis revealed a significant association between baseline HAQ-DI scores and endpoint HAQ-DI scores (??=?0.67, P?<?0.001 and ??=?0.76, P?<?0.001, respectively), 12-month changes in HAQ-DI scores (both ??=?-?0.21, P?<?0.001), and 12-month EQ-5D-3L index scores (??=?-?0.57, P?<?0.001 and ??=?-?0.29, P?=?0.004, respectively). Baseline EQ-5D-3L index scores were significantly associated with 12-month changes in EQ-5D-3L index scores in both groups (??=?-?0.73, P?<?0.001 and ??=?-?0.40, P?=?0.003, respectively). Conclusions:Patients with RA in persistent MDAS experience substantial ongoing physical disability, poor QoL, and pain. HAQ-DI is an important predictor of future disability and reduced QoL, supporting current national recommendations to measure HAQ-DI in routine care.
| S-EPMC7576705 | biostudies-literature
Project description:Background/aimsTo explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA).MethodsThe study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2.ResultsThe median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ.ConclusionBody composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.
| S-EPMC7820641 | biostudies-literature
Project description:ObjectiveTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). To better understand tofacitinib treatment responses, we used group-based trajectory modeling to investigate distinct disease activity trajectories and associated baseline variables in patients with active RA.MethodsThis post hoc analysis used data from a phase III study of methotrexate-naive patients receiving tofacitinib 5 mg twice daily. Changes in the 4-variable Disease Activity Score in 28 joints, using the erythrocyte sedimentation rate (DAS28-ESR) from baseline to month 24 were used in group-based trajectory modeling to identify distinct disease activity trajectories. Patient and disease characteristics, changes in radiographic progression and patient-reported outcomes, and safety up to month 24 were compared among trajectory groups.ResultsFrom 346 methotrexate-naive patients, 5 disease trajectory groups, defined by DAS28-ESR scores, were identified, which progressed from high disease activity (HDA) to remission (group 1, n = 28), to low disease activity (LDA) rapidly (group 2, n = 107), to moderate disease activity (group 3, n = 98), to LDA gradually (group 4, n = 46), or remained in HDA (group 5, n = 67), at month 24. At baseline, groups 1 and 2 generally had lower disease activity and more favorable patient-reported outcomes, compared with other groups. Improvements in radiographic progression and patient-reported outcomes over 24 months were generally consistent with DAS28-ESR-predicted disease activity trajectories. Adverse event rates were generally comparable across groups.ConclusionDistinct phenotypic subgroups identified heterogeneity in patients with RA normally analyzed as a single population. Trajectory modeling may enable separation of clinically meaningful subsets of patients with RA, and may help optimize treatment outcomes.
| S-EPMC9303215 | biostudies-literature
Project description:To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates-gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)-in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.
| S-EPMC4892870 | biostudies-other
Project description:ObjectivesTo investigate whether normal variation of adult height is associated with clinical characteristics in rheumatoid arthritis (RA), including disease activity (DAS28), impairment of joint function (mechanical joint score, MJS) and overall disability (health assessment questionnaire, HAQ).MethodsA cohort (134 males, 287 females) of consecutively recruited RA patients of Northern European origin was studied. Height, weight and demographic information were obtained. A core set of disease measurements, including DAS28, MJS and HAQ, were recorded at baseline, 12 and 24 months. Other clinical variables (e.g. disease duration, IgM rheumatoid factor, antibodies to cyclic citrullinated peptide, C-reactive protein, erythrocyte sedimentation rate) were recorded at baseline. Socioeconomic status, smoking status, comorbid condition, other autoimmune conditions and drug therapy were also recorded. Associations were analyzed using univariate statistics and multivariate linear regression models. Mediation tests were also carried out for evaluating the relationship between gender, height and disease measures.ResultsIn males, height was inversely associated with DAS28, MJS and HAQ (at baseline and over 24 months) independent of other factors (e.g. weight, body mass index, age, disease duration, osteoporosis, autoantibodies, erosive disease, joint replacement, steroid use, smoking status, socioeconomic status and comorbid disease). In females, a similar trend was seen but the relationships were non significant. In the whole population, the association of female gender with more active disease and poor function disappeared after adjustment for height. Mediation analysis indicated that height served as a full mediator in the relationship of gender with disease activity and overall disability. Confirmation of these findings was demonstrated in a second RA population (n?=?288).ConclusionAdult height is inversely associated with disease activity, impairment of joint function and overall disability in RA, particularly in males. The association of female sex with more severe disease activity and disability appears to be mediated by smaller stature.
| S-EPMC3660323 | biostudies-literature
Project description:The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.
| S-EPMC6525860 | biostudies-literature
Project description:BACKGROUND/AIMS:The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. METHODS:This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. RESULTS:A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. CONCLUSION:There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.
| S-EPMC6960052 | biostudies-literature
Project description:ObjectivesTo determine the baseline factors predictive of significant radiographic progression (SRP) in patients with moderately active rheumatoid arthritis (RA) despite receiving methotrexate (MTX).MethodsPatients from the MTX arm of the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes (TEMPO) trial with sustained moderate RA (defined as ≥3.2 mean disease activity score in 28 joints ≤5.1 during the last 6 months of the first year) were analysed for SRP (mTSS >3.0 overall) after 2 and 3 years. Baseline predictors for SRP were identified by univariate and multivariate analyses. All variables shown to be significantly associated with SRP were categorised based on clinically relevant cut-offs and tertiles and were included in a matrix risk model.Results228 patients were assigned MTX treatment, 210 patients were in the radiographic intention-to-treat population, and 96 of these had sustained moderate RA. SRP occurred in 25 (26%) and 33 (34%) patients after 2 and 3 years of MTX treatment, respectively. Univariate and multivariate analyses found that C reactive protein (CRP) and rheumatoid factor (RF) positivity at baseline were predictive of SRP after 2 and 3 years (p<0.05 for all). The matrix risk model showed that RF positivity and CRP levels >40 mg/L at baseline were significantly associated with SRP after 2 (p<0.05 for both; R(2)=0.24) and 3 years (p<0.05 for both; R(2)=0.22). The baseline erosion score was not found to be predictive of SRP.ConclusionsPatients with sustained moderate RA despite receiving MTX treatment are at risk of SRP, with both RF positivity and high CRP levels shown to be predictive of this.
| S-EPMC4613151 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease with fluctuating course of progression. Despite substantial improvement in treatments in recent years, treatment response is still not guaranteed. The aim of this study was to identify variation in Disease Activity Score 28 (DAS28) of RA patients in response to Tocilizumab, and to investigate both molecular and clinical factors influencing response. Clinical and biochemical data for 485 RA patients receiving Tocilizumab in combination with methotrexate were extracted from the LITHE phase III clinical study (NCT00106535), and post-hoc analysis conducted. Latent class mixed models were used to identify statistically distinct trajectories of DAS28 after the initiation of treatment. Biomarker measurements were then analysed cross-sectionally and temporally, to characterise patients by serological biomarkers and clinical factors. We identified three distinct trajectories of drug response: class 1 (n?=?85, 17.5%), class 2 (n?=?338, 69.7%) and class 3 (n?=?62, 12.8%). All groups started with high DAS28 on average (DAS28?>?5.1). Class 1 showed the least reduction in DAS28, with significantly more patients seeking escape therapy (p?<?0.001). Class 3 showed significantly higher rates of improvement in DAS28, with 58.1% achieving ACR response levels compared to 2.4% in class 1 (p?<?0.0001). Biomarkers of inflammation, MMP-3, CRP, C1M, showed greater reduction in class 3 compared to the other classes. Identification of more homogenous patient sub-populations of drug response may allow for more targeted therapeutic treatment regimens and a better understanding of disease aetiology.
| S-EPMC7434906 | biostudies-literature