Rheumatoid Arthritis In Sustained Remission Research Articles

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial

Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. Research Council of Norway and South-Eastern Norway Regional Health Authority.

Patient-reported outcomes and radiographic progression in patients with rheumatoid arthritis in sustained remission versus low disease activity

ObjectiveTo compare clinical and patient-reported outcomes (PROs) over 5 years between patients with rheumatoid arthritis (RA) in sustained remission (sREM), sustained low disease activity (sLDA) or active disease (AD) in...

Performance of the Rheumatoid Arthritis Impact of Disease (RAID) score in relation to flares in disease activity

ObjectivesTo explore the performance of the EULAR-initiated patient-reported Rheumatoid Arthritis Impact of Disease (RAID) questionnaire in relation to flares in disease activity, including comparison with other disease activity outcomes.MethodsPatients with...

Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1g) with piperine (5mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219days (IQR: 123) versus placebo: 214days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumindid not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

Validation and predictive capacity of a Dutch version of the FLARE-RA questionnaire within the context of a TNFi-tapering trial.

Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test-retest reliability were evaluated with Crohnbach's alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test-retest reliability (Cronbach's alpha 0.96; ICC 0.96 [95% CI 0.70-1.00]). Discriminatory capacity of FLARE-RA to detect flares was acceptable (AUC 0.77, 0.80, and 0.72 for global, arthritis, and general symptoms subscales, respectively), with an optimal global score cutoff of 4/10. In GEE-models, higher FLARE-RA scores were associated with increased odds of both current and future flares. We successfully translated and cross-culturally adapted the FLARE-RA into a Dutch version and validated its capacity to detect flares in a bDMARD-tapering context in established RA. Finally, higher FLARE-RA scores might indicate an increased risk of future flares.Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE , EudraCT number 2012-004,631-22. Key Points • Translation and cross-cultural adaptation of the FLARE-RA resulted in a Dutch version with excellent internal consistency and test-retest reliability. • The FLARE-RA is a valid instrument to detect current OMERACT-defined flares within a bDMARD tapering setting, with an optimal global score cutoff of 4/10. • Higher scores on the FLARE-RA are associated with increased risk of future flares, which could be particularly relevant when considering DMARD tapering.

OP0084 DIGITAL SPATIAL PROFILING REVEALS DISTINCT SYNOVIAL TISSUE MACROPHAGE TRANSCRIPTOMIC SIGNATURE OF SUSTAINED REMISSION IN RHEUMATOID ARTHRITIS PATIENTS AT RISK OF DISEASE FLARE AFTER TREATMENT CESSATION

BackgroundSustained remission is the treatment goal for Rheumatoid Arthritis (RA) and once achieved patients are eligible to treatment tapering or discontinuation. However, this exposes patients to the occurrence of unpredictable disease flare, and to date there are no definitive predictive biomarkers of flare for RA in remission that could be used in clinical practice.ObjectivesTo assess the impact of clinical classification of remission on synovial tissue (ST) features of RA in sustained remission and to identify predictive biomarkers of disease flare.Methods200 RA in sustained clinical (102 RA with DAS&lt;1.6 and 98 RA fulfilling Boolean remission criteria for at least 9 months, respectively) and ultrasound (US) remission (PD negative) under Methotrexate with or without biological-Disease Modifying Anti-Rheumatic Drugs (bDMARDs) were enrolled and underwent to US guided ST biopsy. 373 naive RA were included as comparison. For each patient, synovitis degree was determined using a H&amp;E-based semiquantitative score1. Some ST samples of remission RA were used for synovial tissue macrophage (STMs)(CD206/MerTK) FACS phenotyping and digital spatial profiling (GeoMx DSP, Nanostring) to quantitate transcript abundance of CD68pos cells in 138 spatially distinct ST regions of interest (ROI). After study entry, RA were randomly assigned to tapering/discontinuation (TAP/DISC) (tapering c- or b-DMARD treatment for 6 months and discontinuing c- or bDMARD afterwards) or maintaining the same therapeutic scheme (CONT). Each RA was followed every 3 months to assess flare rate after treatment modifications for 24 months.ResultsRegardless of either DAS- or Boolean-defined, remission patients had significantly lower KSS than naive RA (p&lt;0.0001 for both). However, ST of RA in Boolean remission had lower KSS (p&lt;0.0001) and was enriched in CD206posMerTKpos STMs (p=0.0012) as compared to DAS-defined remission RA. 73(36.5%) RA experienced a disease flare regardless of the treatment change during 24 months follow-up. Stratifying RA in remission based on remission definition and treatment group, DAS-defined remission RA who had a disease flare within at least 6 months follow-up had, at study entry, significantly higher KSS (p&lt;0.0001) than RA who maintained a sustained remission, regardless of the treatment change (CONT:p=0.0027 and TAP/DISC:p=0.0011). Logistic regression analysis revealed that baseline KSS≥3 [AUC:0.748(95%CI:0.649-0.846)p&lt;0.0001] was an independent predictive factor of disease flare [OR:6.9(95%CI:2.82-16.81)] within 24 months follow-up in DAS-defined remission RA. Conversely, RA in Boolean remission did not differ for KSS at study entry in both the CONT (p&gt;0.05) and the TAP/DISC (p&gt;0.05) group in relation to disease flare. However, considering STMs phenotype, RA in Boolean remission in the TAP/DISC group who had low levels of CD206posMerTKpos (&lt;38.1%), experienced more likely a disease flare compared to RA in the CONT subgroup with CD206posMerTKpos≥38.1% (p=0.0014). Logistic regression analysis confirmed that, before treatment change, STMs phenotype (CD206posMerTKpos &lt;38.1%) in RA in remission is an independent predictor of disease flare [OR:6.25(95%CI:1.33-29.43)] within 24 months. Finally, DSP analysis using CD68 morphology marker, revealed that lining and sublining layer CD68pos spatial transcriptomics distinguished, at baseline, remission RA who flared after treatment modification from those who did not.ConclusionDisease flare is a common event in RA in sustained remission after treatment modification. KSS and STMs phenotype identified by flow cytometry or by tissue spatial transcriptomic can identify RA in remission at higher risk of flare after treatment modification. Thus, spatial transcriptomic with defined panel of markers on histological biopsy tissues could be a way forward in predicting disease flare.

Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial.

Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms. RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score <2·6 units). Eligible patients were recruited consecutively from 14 German hospitals or rheumatology practices and randomly assigned (1:1:1) without stratification and regardless of baseline treatment, using a sequence that was computer-generated by the study statistician, to continue 100% dose DMARD (continue group), taper to 50% dose DMARD (taper group), or 50% dose DMARD for 6 months before stopping DMARDs (stop group). Neither patients nor investigators were masked to the treatment assignment. Patients were assessed every 3 months and screened for disease activity and relapse. The primary endpoint was the proportion of patients in sustained DAS28-ESR remission without relapse at 12 months, analysed using a log-rank test of trend and Cox regression. Analysis by a trained statistician of the primary outcome and safety was done in a modified intention-to-treat population that included participants with non-missing baseline data. This study is completed and closed to new participants and is registered with ClinicalTrials.gov (NCT02779114). Between May 26, 2010, and May 29, 2018, 303 patients were enrolled and allocated to continue (n=100), taper (n=102), or stop DMARDs (n=101). 282 (93%) of 303 patients were analysed (93 [93%] of 100 for continue, 93 [91%] of 102 for taper, and 96 [95%] of 101 for stop). Remission was maintained at 12 months by 81·2% (95% CI 73·3-90·0) in the continue group, 58·6% (49·2-70·0) in the taper group, and 43·3% (34·6-55·5) in the stop group (p=0·0005 with log-rank test for trend). Hazard ratios for relapse were 3·02 (1·69-5·40; p=0.0003) for the taper group and 4·34 (2·48-7·60; p<0.0001)) for the stop group, in comparison with the continue group. The majority of patients who relapsed regained remission after reintroduction of 100% dose DMARDs. Serious adverse events occurred in ten of 93 (11%) patients in the continue group, seven of 93 (8%) patients in taper group, and 13 of 96 (14%) patients in the stop group. None were considered to be related to the intervention. The most frequent type of serious adverse event was injuries or procedural complications (n=9). Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approaches will require tight monitoring of disease activity. However, remission was regained after reintroduction of antirheumatic treatments in most of those who relapsed in this study. These results might help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis. None.

Tapering of Etanercept is feasible in patients with Rheumatoid Arthritis in sustained remission: a pragmatic randomized controlled trial

Objective In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. Method Patients with RA in 28-joint Disease Activity Score (DAS28) remission (≥ 6 months) and treated with etanercept 50 mg weekly (≥ 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28–C-reactive protein (CRP) ≥ 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. Results Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0–6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. Conclusions Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment?

With increasing numbers of patients with rheumatoid arthritis achieving sustained remission, medication withdrawal is an important consideration to reduce polypharmacy and associated adverse events. An article from the journal Arthritis & Rheumatology (1) explores the treatment withdrawal options for patients on etanercept and methotrexate combination therapies and suggests methotrexate withdrawal has the least impact on disease worsening. There are limitations in the study, including the use of only one disease activity score and no assessment of radiographic progression, but, overall, the article provides a good framework for future studies on treatment withdrawal options and the possibility of medication reduction for patients.

Distinct synovial tissue macrophage subsets regulate inflammation and remission in rheumatoid arthritis.

Immune-regulatory mechanisms of drug-free remission in rheumatoid arthritis (RA) are unknown. We hypothesized that synovial tissue macrophages (STM), which persist in remission, contribute to joint homeostasis. We used single-cell transcriptomics to profile 32,000 STMs and identified phenotypic changes in patients with early/active RA, treatment-refractory/active RA and RA in sustained remission. Each clinical state was characterized by different frequencies of nine discrete phenotypic clusters within four distinct STM subpopulations with diverse homeostatic, regulatory and inflammatory functions. This cellular atlas, combined with deep-phenotypic, spatial and functional analyses of synovial biopsy fluorescent activated cell sorted STMs, revealed two STM subpopulations (MerTKposTREM2high and MerTKposLYVE1pos) with unique remission transcriptomic signatures enriched in negative regulators of inflammation. These STMs were potent producers of inflammation-resolving lipid mediators and induced the repair response of synovial fibroblasts in vitro. A low proportion of MerTKpos STMs in remission was associated with increased risk of disease flare after treatment cessation. Therapeutic modulation of MerTKpos STM subpopulations could therefore be a potential treatment strategy for RA.

A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis

BackgroundReliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission.MethodsRA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as ‘low disease activity state’ (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as ‘persistent disease activity’ (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test.ResultsOf 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68–0.75) and IR/SR (AUROCs 0.65–0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65–0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year.ConclusionsThis study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.

Potential of neutrophil to lymphocyte ratio in predicting sustained remission in rheumatoid arthritis compared to other immune activation markers.

Background & objectives:Cells and cell proportions may indicate the equilibrium status of the immune system. The present study was conducted to evaluate the role of cytokines and the immunocompetent cells as biomarkers of remission in rheumatoid arthritis (RA) patients intended to withdraw or reduce disease-modifying anti-rheumatic drug (DMARD) treatment.Methods:This prospective observational study involved newly diagnosed and treated RA patients who fulfilled 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. The patients were classified based on disease activity score (DAS)28-C-reactive protein (CRP)(3) score into remission (≤2.6) and treatment-naïve/active (>2.6) groups. Remission patients were followed up for six months and were reclassified into those in sustained remission (≤2.6) and relapse (>2.6) based on the DAS28-CRP(3) score. Various cytokines and cell surface markers were quantitated using whole blood samples, and the CD3+/CD19+ and FOXP3+/CD4+ ratios were calculated. The clinical, demographic, cytokine and cellular phenotype characteristics were compared between remission and treatment-naïve groups. The factors associated with sustained remission were verified.Results:Of the 72 patients, 52 were in remission and 20 were DMARD naïve and had active disease. Duration of illness, interleukin-6 (IL-6) and IL-10 were significantly different between remission and treatment naïve/active disease patients. Increased likelihood for achieving sustained remission was noted in RA patients with baseline NLR ≤2. Other demographic/clinical variables and cell phenotypes, namely age, gender, duration of illness, CD3+, CD4+, FOXP3+, CD19+, CD3+/CD19+, FOXP3+/CD4+ and cytokines - IL-6 and IL-10 were not associated with sustained remission.Interpretation & conclusions:The present preliminary study highlighted the potential of NLR in predicting sustained remission in RA patients with a cut-off <2. Further study with a large sample size should be done to confirm this finding.

Correction: Prevalence and predictors for sustained remission in rheumatoid arthritis

[This corrects the article DOI: 10.1371/journal.pone.0214981.].

Secular trends of sustained remission in rheumatoid arthritis, a nationwide study in Sweden.

The aim of this study of patients with RA in Sweden was to investigate secular trends in achieving sustained remission (SR), i.e. DAS28 <2.6 on at least two consecutive occasions and lasting for at least 6 months. All adult RA patients registered in the Swedish Rheumatology Quality register through 2012, with at least three registered visits were eligible, a total of 29 084 patients. Year of symptom onset ranged from 1955, but for parts of the analysis only patients with symptom onset between 1994 and 2009 were studied. In total, 95% of patients fulfilled the ACR 1987 classification criteria for RA. Odds of reaching SR for each decade compared with the one before were calculated with logistic regression and individual years of symptom onset were compared with life table analysis. Of patients with symptom onset in the 1980s, 1990s and 2000s, 35.0, 43.0 and 45.6% reached SR, respectively (P < 0.001 for each increment), and the odds of SR were higher in every decade compared with the one before. The hazard ratio for reaching SR was 1.15 (95% CI 1.14, 1.15) for each year from 1994 to 2009 compared with the year before. Five years after symptom onset in 2009, 45.3% of patients had reached SR compared with 15.9% in 1999. There is a clear secular trend towards increased incidence of SR in patients with RA in Sweden. This trend most likely reflects earlier diagnosis and treatment start, and adherence to national and international guidelines recommending the treat to target approach.

Predictors and the optimal duration of sustained remission in rheumatoid arthritis.

To determine predictors and optimal duration of sustained remission (SR) in patients with rheumatoid arthritis (RA). A total of 428 consecutive patients with RA visiting our clinic routinely between 2012 and 2013 were evaluated. Seventy seven of these patients in DAS28 remission were enrolled and followed up for 62.2 ± 9.9months. Patients in remission ≥ 6months (SR) and shorter (non: N-SR) were compared in terms of demographic-clinical data and the psychosocial factors. At enrollment, 1st and 5th years, patients in DAS28, SDAI, and Boolean remission were determined. Sixty three patients were in SR and 14 in N-SR. Lower baseline DAS28 and HAQ scores, anti-CCP were positive predictors of SR. Although the presence of anxiety, depression, fibromyalgia, and fatigue were lower in the SR group, there was no significance. Patients in DAS28 remission (100%) at baseline reduced to 64% at 1st and 42.6% at 5th years. Patients satisfying SDAI and Boolean remission at these three visits were 49%, 44%, and 32.4% vs 41%, 28%, and 20.6%, respectively. If the duration of remission is defined as 6months, the remission rates of SDAI at inclusion and fifth years' visits were similar but Boolean remission rates differed significantly and if it is accepted as ≥ 12months, both the SDAI and Boolean remission rates were not different. Low DAS28 and HAQ scores at baseline, anti-CCP were positive predictors of SR. Instead of 6months, remission duration for ≥ 12months would probably help us to predict SR independently from the chosen criteria; Boolean or SDAI.

Clinical Course and Sustained Remission in Rheumatoid Arthritis

Clinical Course and Sustained Remission in Rheumatoid Arthritis

The application value of MRI in the diagnosis of subclinical inflammation in patients with rheumatoid arthritis in remission

BackgroundTo explore the value of MRI in the diagnosis of subclinical inflammation in patients with early rheumatoid arthritis (RA) in remission and to predict the radiographic progression.MethodsA total of 76 of 156 patients with early RA in remission at 1 year and with available magnetic resonance imaging (MRI) data at baseline and at 12 months were included. Complete clinical and laboratory evaluations were conducted for the patients. MRI images were assessed according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Progression of bone erosions was defined as an increase of 1 or more units in annual RAMRIS score for erosions compared to baseline.ResultsAt 1 year, the majority of patients with RA in sustained remission showed some inflammatory activity on MRI (43.4% synovitis, 39.5% bone marrow edema (BME), and 9.2% tenosynovitis), and 25 of the 76 patients (32.9%) showed MRI progression of bone erosions. A significant difference was observed in MRI BME and bone erosion at 1 year, with higher mean score in patients with progression compared to non-progression of erosions (BME, 4.8 ± 3.6 vs 3.1 ± 2.1, P = 0.01; bone erosion, 13.5 ± 9.6 vs 4.4 ± 3.6, P < 0.001).ConclusionPersistent subclinical inflammations were shown in patients with sustained remission; BME in MRI may be a strong predictor of future radiographic progression of bone erosions in patients with persistent clinical remission.

Prevalence of sustained remission in rheumatoid arthritis: impact of criteria sets and disease duration, a Nationwide Study in Sweden.

The aims of this national study in Sweden of patients with RA were to: examine the prevalence of sustained remission (SR), that is, remission lasting for at least 6 months; compare the prevalence of SR in patients with early RA and established RA; study the timing of onset of and time spent in SR; and study possible predictors of SR. Adult patients with RA included in the Swedish Rheumatology Quality registry were studied. The registry was searched for patients fulfilling remission criteria: DAS28-ESR, Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and ACR/EULAR remission for at least 6 months. Early RA was defined as symptom duration ⩽6 months at inclusion in the Swedish Rheumatology Quality. Of 29 084 patients, 12 193 (41.9%) reached DAS28 SR at some time point during follow-up compared with 6445 (22.2%), 6199 (21.3%) and 5087 (17.5%) for CDAI, SDAI and ACR/EULAR SR, respectively. SR was more common in early RA (P < 0.001). The median time from symptom onset to SR was 1.9, 2.4, 2.4 and 2.5 years according to DAS28, CDAI, SDAI and ACR/EULAR criteria, respectively. Lower age, male sex and milder disease characteristics were associated with SR. The majority of patients in this nationwide study never reached SR. Patients with early RA are more likely to reach SR than patients with established RA.

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis

Objectives: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission.Methods: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 – erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits.Results: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five.Conclusion: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations.

Sustained remission is an ultimate treatment goal in the management of patients with rheumatoid arthritis (RA). Historically the frequency of sustained remission was low but the frequency of achieved sustained remission is increasing over time. The last years’ clinical studies of tight control targeted treatment and intervention trials of early use of intensive strategy suggest that these treatment strategies are associated with higher rates of sustained remission. Achievement of sustained remission, in particular but not limited to early sustained remission, can provide tapering and stopping disease-modifying antirheumatic drugs (DMARDs). With new treatment strategies drug-free sustained remission is becoming an achievable goal. Sustained remission is associated with improved outcomes in regard to function, patient-reported outcomes and survival. Drug-free sustained remission is characterized by normalized function ability and survival. Sustained remission and, in particular, drug-free sustained remission offer hope that early identification of patients with arthritis, early improved novel treatments and treatment with target to achieve remission may potentially transform the progressive course of RA disease and disrupt RA chronicity.In this review we summarize the recent evidence on sustained remission in patients with RA, treatment strategies to achieve sustained remission, management of patients in sustained remission and significance of sustained remission from the patient perspective.