Progression Of Radiological Damage Research Articles

DMARDs-Gut Microbiota Feedback: Implications in the Response to Therapy.

Due to its immunomodulatory effects and the limitation in the radiological damage progression, disease-modifying antirheumatic drugs (DMARDs) work as first-line rheumatoid arthritis (RA) treatment. In recent years, numerous research projects have suggested that the metabolism of DMARDs could have a role in gut dysbiosis, which indicates that the microbiota variability could modify the employment of direct and indirect mechanisms in the response to treatment. The main objective of this review was to understand the gut microbiota bacterial variability in patients with RA, pre and post-treatment with DMARDs, and to identify the possible mechanisms through which microbiota can regulate the response to pharmacological therapy.

Association of Dickkopf-1 Polymorphisms With Radiological Damage and Periodontal Disease in Patients With Early Rheumatoid Arthritis: A Cross-Sectional Study.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that increased bone resorption. Periodontal disease (PD) is an associated risk factor of RA. Studies suggest an association between bone markers such as the dickkopf-related protein 1 (DKK-1) and progression of radiological damage. We aimed to evaluate the marker DKK-1, its polymorphisms in patients with early rheumatoid arthritis (eRA), and its association with rheumatic, radiological, and periodontal variables. This is a cross-sectional study. Samples were obtained from 63 patients with eRA. Radiographs of hands and feet were evaluated by Sharp-van der Heijde score (SHS) and Simple Erosion Narrowing Score (SENS). Serum DKK-1 levels and high-resolution fusion analysis was used for polymorphisms (rs1896368, rs1896367, rs1528873). Bivariate analyses were performed. Individuals heterozygous for rs1896367 had more frequent erosions (p = 0.026) and joint space narrowing (p = 0.005) in the feet, higher SHS (p = 0.016), and higher SENS (p ≤ 0.001). Patients homozygous for rs1896368 had less frequent joint space narrowing in hands and feet as assessed by SHS and less presence of erosions by SENS (odds ratio, 0.04; 95% confidence interval, 0.00-0.93; p < 0.05). The presence of PD was associated with the homozygous of rs1896367 (p = 0.009) and the heterozygous of rs1896368 (p = 0.033). Polymorphism rs1896367 seems to be associated with greater radiological compromise; rs1896368 confers protection against bone damage in Colombian eRA patients.

Comparison between low disease activity or DAS remission as treatment target in patients with early active rheumatoid arthritis

ObjectivesTo compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA).MethodsFive-year outcomes were compared in 133 patients with early...

Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.

To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

What have we learned from BeSt?

BackgroundHow have the long term outcomes of RA improved in the last decade? MethodsPatients with DMARD naïve RA were randomized to 4 treatment strategies: 1. sequential DMARD monotherapy, 2. step-up combination therapy, 3. initial combination therapy including prednisone or 4. including infliximab. Treatment-to-target was aimed at DAS≤2.4 (three-monthly calculations). Functional ability (HAQ), radiologic damage progression (Sharp/vanderHeijde Score) and overall survival were reported. ResultsPatients in arms 3 and 4 showed earlier clinical improvement. Up to 50% achieved DAS-remission (<1.6), up to 29% achieved drug free remission. Damage progression was well suppressed (median after 10years in completers 2 SHS points), functional ability approached normality (mean HAQ 0.6). There was no increased mortality (Standardized Mortality Ratio 1.16, 95% CI 0.92–1.46). ConclusionsEarly treatment determines early clinical improvement, treatment-to-target determines long term outcomes. Prevention of relevant radiologic damage progression and disability, drug free remission and normalized survival are realistic goals.

Validation of automatic joint space width measurements in hand radiographs in rheumatoid arthritis.

Computerized methods promise quick, objective, and sensitive tools to quantify progression of radiological damage in rheumatoid arthritis (RA). Measurement of joint space width (JSW) in finger and wrist joints with these systems performed comparable to the Sharp-van der Heijde score (SHS). A next step toward clinical use, validation of precision and accuracy in hand joints with minimal damage, is described with a close scrutiny of sources of error. A recently developed system to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was validated in consecutive hand images of RA patients. To assess the impact of image acquisition, measurements on radiographs from a multicenter trial and from a recent prospective cohort in a single hospital were compared. Precision of the system was tested by comparing the joint space in mm in pairs of subsequent images with a short interval without progression of SHS. In case of incorrect measurements, the source of error was analyzed with a review by human experts. Accuracy was assessed by comparison with reported measurements with other systems. In the two series of radiographs, the system could automatically locate and measure 1003/1088 (92.2%) and 1143/1200 (95.3%) individual joints, respectively. In joints with a normal SHS, the average (SD) size of MCP joints was [Formula: see text] and [Formula: see text] in the two series of radiographs, and of PIP joints [Formula: see text] and [Formula: see text]. The difference in JSW between two serial radiographs with an interval of 6 to 12 months and unchanged SHS was [Formula: see text], indicating very good precision. Errors occurred more often in radiographs from the multicenter cohort than in a more recent series from a single hospital. Detailed analysis of the 55/1125 (4.9%) measurements that had a discrepant paired measurement revealed that variation in the process of image acquisition (exposure in 15% and repositioning in 57%) was a more frequent source of error than incorrect delineation by the software (25%). Various steps in the validation of an automated measurement system for JSW of MCP and PIP joints are described. The use of serial radiographs from different sources, with a short interval and limited damage, is helpful to detect sources of error. Image acquisition, in particular repositioning, is a dominant source of error.

Effectiveness of a telemonitoring intensive strategy in early rheumatoid arthritis: comparison with the conventional management approach.

BackgroundThe advent of Internet and World Wide Web has created new perspectives toward interaction between patients and healthcare professionals. Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to guide the collaborative management treatment and improve outcomes in patients. The objective of this study was to investigate whether an intensive treatment strategy, according to a telemonitoring protocol, is more effective than conventional management strategy in reaching remission and comprehensive disease control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients.MethodsForty-four ERA patients were randomly allocated into two groups: the telemonitoring intensive strategy (TIS) group (group 1) or the conventional strategy (CS) group (group 2). Three patients refused to participate. In group 1 (n = 21), a remote monitoring system of disease activity, in combination with protocolised treatment adjustments aiming for remission was applied. In group 2 (n = 20), patients were treated according to daily clinical practice, with regular evaluation of disease activity, but without protocolised treatment adjustments. A telemedical care called “REmote TElemonitoring for MAnaging Rheumatologic Condition and HEaltcare programmes” (RETE-MARCHE), was developed to perform the remote monitoring.ResultsA higher percentage of patients in the TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at year 1, p <0.01). Time to achieve remission was significantly shorter in the group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %) and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate of CDC (19.4 % vs 5 %).ConclusionsAccording to our results, an intensive treatment strategy by telemonitoring leads to more effective disease remission and more rapid CDC than treatment according to conventional management strategy in ERA.Trial registrationTrial registration number: ISRCTN13142685Date of registration: March, 17th 2016

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study).

BackgroundEarly suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients.MethodsPatients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA.ResultsAfter 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0–0).ConclusionsAfter 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed.Trial registrationhttp://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0912-y) contains supplementary material, which is available to authorized users.

FRI0065 Residual power doppler signals during clinical remission determine joint prognosis in rheumatoid arthritis

Background“Clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA). However, there is evidence that subclinical synovitis is associated with progression of structural damage even after achieving...

THU0156 Response of ra on MRI-detected synovitis to double filtration plasmapheresis

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease with a poor prognosis in which synovitis induces progressive destruction of bones and joints, which leads to marked impairment of the...

SAT0520 Ultrasonography is Useful for Predicting Boolean Remission after Achieving DAS28-Based Clinical Remission of Rheumatoid Arthritis

BackgroundAlthough “clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA), its definition is still controversial. In fact, progressive joint destruction is often observed even during persistent...

SP0141 Collaboration Between Primary and Secondary Care: Early Detection of Inflammatory Arthritis

Inflammatory arthritis is common and costly for individuals, health services and societies. Current guidelines for the management of inflammatory highlight the importance of early administration of disease modifying medication and...

SAT0003 Relationship Between Anticitrullinated Protein Antibodies and Clinical Remission in Arthritis

BackgroundThe relationship between anticitrullinated protein antibodies (ACPA) and the clinical outcome of rheumatoid arthritis (RA) under treatment has been evaluated in clinical trials with conflicting results. Thus, an analysis of...

OP0154 Clinical and radiological outcomes of four disease activity driven treatment strategies: 8-year results of the best study

ObjectivesTo compare clinical and radiological outcomes of 8 years targeted treatment with four treatment strategies in recent onset rheumatoid arthritis (RA) patients.MethodsPatients (n=508) with recent onset RA were randomized to...

Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study)

ObjectiveTo assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo.Methods110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for...

Prediction of treatment response by anticitrullinated protein antibodies (ACPA) levels among patients with rheumatoid arthritis

Background The relationship between ACPA and the clinical outcome of rheumatoid arthritis (RA) under treatment has been evaluated in clinical trials with conflicting results. Thus, the response to treatment was influenced by ACPA in the BeSt study. However, radiological damage progression was more likely among ACPA-positive patients. Conversely, ACPA-negative patients achieved less remissions in the IMPROVED study. Because of these, we evaluated the clinical response (CR) of patients with RA receiving treatment according to ACPA titers. Patients and methods All patients seen at our Unit who fulfilled the following criteria were included in this retrospective study: 1) Diagnosis of RA by a rheumatologist meeting the 1987 criteria for RA; 2) Available determinations of ACPA; 3) Treatment for AR (whether or not biological therapy) with a minimum follow up of 6 months. The outcome variable was CR defined as reaching DAS28 <1.6. Predictors of CR were evaluated using logistic regression. Results 71 patients were included, 79% of them women. CR was observed in 19 (27%) patients during the first 12 months of follow-up. Baseline median (IQR) ACPA levels were 306 (7-500) for individuals without CR and 76 (7-153) for those with CR (p=0.022). 29 (56%) patients without CR vs. 5 (26%) with CR showed ACPA levels ≥200 (p=0.028). ACPA levels decreased significantly among patients with CR (p=0.019), but they did not change in those without CR (p=0.330). Factors independently associated with CR were: recent onset RA [adjusted odds ratio (AOR) 0.19; 95% confidence interval (95%CI) 0.41-0.90; p=0.036], baseline ACPA levels ≥200 [AOR 6.48; 95%CI 1.12-37.3; p=0.037], baseline CRP levels [per unit increase; AOR 1.06; 95%CI 1.001-1.12; p=0.048], baseline DAS28 [per unit increase; AOR 3.04; 95%CI 1.3-7.4; p=0.014]. Conclusions ACPA levels can predict CR of patients with RA receiving treatment in real life conditions. Individuals with high ACPA levels may benefit from a more aggressive treatment approach. Titers of ACPA may be useful to monitor the clinical activity of RA.

Towards personalized treatment: predictors of short-term HAQ response in recent-onset active rheumatoid arthritis are different from predictors of rapid radiological progression

Objective: Personalized treatment depends on the treatment goals. Current prediction models to guide initial treatment choices focus on radiological damage progression. However, for some patients this outcome is less relevant, whereas short-term functional ability is relevant to all. Do these various treatment goals share the same predictors?Methods: Data for 497 patients from the Dutch Behandel Strategieen (BeSt) study of treatment strategies for early rheumatoid arthritis (RA), randomized to initial monotherapy or combination therapy, were used. Predictors of short-term functional disability [Health Assessment Questionnaire (HAQ) score ≥ 1 after 3 months of treatment] were identified with logistic regression analyses. Predicted risks of a HAQ score ≥ 1 were determined for each treatment group and for each subpopulation.Results: At baseline, 76% of patients had a HAQ score ≥ 1 (mean 1.7 ± 0.5). After 3 months of treatment this score was achieved by 40% (mean HAQ score 1.5 ± 0.5). Baseline HAQ score, pain, the Ritchie Articular Index (RAI), and treatment group were significant independent predictors for a HAQ score ≥ 1; the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and baseline radiological damage were not. With cut-offs of 35% and 60%, the risk of a HAQ score ≥ 1 was high for 47% and low for 20% of the patients treated with initial monotherapy. Risks were markedly reduced in the combination therapy groups, also in unfavourable risk profiles.Conclusion: In recent-onset active RA, baseline HAQ score, pain, and initial treatment are predictors for a HAQ score ≥ 1 after 3 months. Known predictors of radiological damage were not predictive of short-term functional disability. The choice of the best initial treatment thus depends on the relevance of various outcome measures for an individual patient.

The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study

ObjectiveAnticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment...

Biologic therapy with anti-TNFa in rheumathoid atrhritis

To evaluate the efficacy, the tolerability, and treatment survival of the association of anti-TNFα (Infliximab, Etanercept, Adalimumab) plus Methotrexate vs Methotrexate as monotherapy in patients with reumathoid arthritis (RA). Review of published controlled randomized clinical studies on the association of anti-TNFα plus Methotrexate vs Methotrexate alone in patients with rheumathoid arthritis (RA). Results in terms of remission and progression of radiologic damage, and clinical response expressed in terms of ACR 50 or ACR 70 were reviewed in the different studies. In patients with RA the association of anti-TNFα plus Methotrexate led to a greater remission of radiologic damage and marked improvement of clinical response expressed as ACR 50 or ACR 70 compared to therapy with Methotrexate only. In the absence of controlled studies, review of the published studies showed that in RA patients the association of anti-TNFα plus Methotrexate is extremely more efficacious than therapy with Methotrexate only. Choice of the drug depends on the activity of the disease, the necessity of a fast response, the presence of side effects, the schedule of treatment and consequently the direct and indirect costs of the drug, and the easiness on supply and distribution.

Association with joint damage and physical functioning of nine composite indices and the 2011 ACR/EULAR remission criteria in rheumatoid arthritis

ObjectiveTo compare nine disease activity indices and the new American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) remission criteria in rheumatoid arthritis (RA) and to relate these to physical...