Though remission is currently a treatment goal in patients with rheumatoid arthritis (RA), the number of patients who achieve and sustain remission in daily practice is still small. It is suggested that early remission will be associated with sustainability of remission. The aim was to study the association between time-to-remission and sustainability of remission in a cohort of early RA patients treated according to daily practice.
For this study, three-year follow-up data were used from the Nijmegen RA Inception Cohort of patients included between 1985 and 2005 (N = 753). Patients were included upon diagnosis (ACR criteria), were systematically evaluated at three-monthly visits and treated according to daily practice. Remission was defined according to the Disease Activity Score (DAS) <1.6 and the ACR remission criteria. Remission of at least 6 months duration was regarded as sustained remission. Predictors for time-to-remission were identified by Cox-regression analyses. The relation between time-to-remission and sustained remission was analyzed using longitudinal binary regression.
N = 398 (52%) patients achieved remission with a median time-to-remission of 12 months. Male gender, younger age and low DAS at baseline were predictive to reach remission rapidly. There were n = 142 (36%) patients experiencing sustained remission, which was determined by a shorter time-to-remission only. The relationship between time-to-remission and sustained remission was described by a significant odds ratio (1.11) (1.10 to 1.12-95% CI) that was constant over the whole period 1985 to 2005. Results obtained with the ACR remission criteria were similar.
A shorter time-to-remission is related to sustainability of remission, supporting striving for early remission in patients with RA.
In development of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) remission definitions using clinical trials data, one criterion used to compare different remission definitions was whether, compared with those not in remission, those in remission had evidence of later disease stability defined by x-ray and functional status. Validation of the RA remission criteria using observational study data is necessary before recommending their use in practice.
Using data from those who met RA criteria in the ESPOIR cohort, we matched each person in remission with a person not in remission and then carried out analyses comparing later stability of x-ray and health assessment questionnaire (HAQ) between the two groups. We compared the predictive validity of the same candidate definitions of remission evaluated in the ACR/EULAR process. To minimize potential bias and produce more stable results, we used a bootstrap resampling approach to select those not in remission, repeating the sample matching analysis process 500 times.
Results were similar to those of clinical trials analyzed for the ACR/EULAR remission criteria. Specifically, the ACR/EULAR remission definitions using either an simple disease activity index (SDAI) ≤ 3.3, clinical disease activity index (CDAI) ≤ 2.8 or a definition of remission requiring tender joint count, swollen joint count, patient global assessment all ≤ 1 performed as well or better than other candidate definitions of remission in terms of predicting later x-ray and function stability.
ACR/EULAR definitions of remission developed for trials are similarly valid in observational studies in RA and could be used in practice.
Due to advances in therapies for rheumatoid arthritis (RA) over the last years, an increasing proportion of patients are able to achieve a state of ‘remission’. But what exactly is remission? At the moment, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient’s disease state. For research findings to be correctly interpreted, the need for a uniform definition of remission is vital. The ACR constituted a committee to redefine remission in RA that included international clinical researchers, trialists and clinical epidemiologists. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of ‘remission’, and develop a research agenda that would inform future work in the development of an ACR definition of remission.
In its first meeting, the committee preferred to develop a ‘strict’ definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome e.g. physical function and damage. The committee decided to consider both a definition for trials and a modified version for clinical practice.
The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis.
698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis.
After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids.
Early remission of rheumatoid arthritis by 28‐joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.
Objectives: To study which cut off point of DAS28 corresponds to fulfilment of the American Rheumatism Association (ARA) preliminary remission criteria, and clinical remission criteria in patients with rheumatoid arthritis (RA).
Methods: All adult patients diagnosed with RA at Jyväskylä Central Hospital 1997–98 were assessed for remission at 5 years. Remission was defined as (a) ARA remission; (b) clinical remission (defined as no tender or swollen joints and normal erythrocyte sedimentation rate). DAS28 was used to measure disease activity. A receiver operating characteristics curve analysis was performed to calculate a cut off point of DAS28 that best corresponds to the ARA remission criteria and the clinical remission criteria.
Results: 161 patients (mean age 57 years, 107 (66%) female, 98 (61%) with positive rheumatoid factor, and 51 (32%) with erosions) were studied. At 5 years, 19 (12%) patients met the ARA remission criteria, and 55 (34%) met the clinical remission criteria. The cut off value of DAS28 was 2.32 for the ARA remission criteria, and 2.68 for the clinical remission criteria. In patients with DAS28 <2.32, 11/57 (19%) had tender joints, 6/57 (11%) had swollen joints, and 4/57 (7%) had both tender and swollen joints (66 joint count).
Conclusion: In this study the DAS28 cut off point for the ARA remission was lower than in previous studies. The cut off point for DAS28 remission remains controversial. A substantial proportion of patients below the DAS28 cut off point for remission have tender or swollen joints, or both. DAS28 may not be an appropriate tool for assessment of remission in RA.
Remission is rapidly becoming a key endpoint in rheumatoid arthritis clinical trials, but its definition is not satisfactory. Although it is generally believed that achieving a state of remission will lead to better structural outcome, this has not been studied systematically. As a part of an undertaking to redefine remission, the current review describes the relationship between remission and long term structural outcome.
A systematic literature search of PubMed, Embase.com, and the Cochrane Library intersected three groups of terms: rheumatoid arthritis, remission and long term outcome. The search identified 1138 records, of which 14 were relevant to the research question.
All the studies included in this review showed a relationship between remission and long term structural damage or disability. Patients that achieved a state remission, defined in various ways, showed less deterioration of function and radiographic progression compared to patients who did not reach a state of remission.
Patients who achieve a state of remission are less likely to show deterioration of function and radiographic progression compared to patients that do not reach a state of remission.
Rheumatoid arthritis; remission; systematic review; predictive validity
The presence or absence of antibodies to citrullinated peptides/proteins (ACPA) is an important parameter that helps a clinician set a diagnosis of early rheumatoid arthritis and, hence, initiate treatment. There are several commercial tests available to measure ACPA levels, although it can be difficult to decide what the best test for a given clinical question is. We analyzed literature data in which the diagnostic and other properties of various ACPA tests are compared. The results show that for diagnostic purposes the CCP2 test has the highest specificity, the highest sensitivity in stratified studies and the highest positive predictive value. For the prediction of future joint destruction the CCP2, MCV, and CCP3 tests may be used. The ability to predict the likelihood of not achieving sustained disease-modifying antirheumatic drug-free remission was highest for the CCP2 test. Finally, the levels of anti-CCP2 and anti-CCP3 (and possibly anti-mutated citrullinated vimentin) in rheumatoid arthritis patients are not significantly influenced by TNFα blocking agents.
To seek the cutoff value of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) that is necessary to achieve remission under the new Boolean-based criteria, we analyzed the data for 285 patients with rheumatoid arthritis registered between May 2008 and November 2009 by the Michinoku Tocilizumab Study Group and observed for 1 year after receiving tocilizumab (TCZ) in real clinical practice. Remission rates under the DAS28-ESR criteria and the Boolean criteria were assessed every 6 months after the first TCZ dose. The DAS28-ESR cutoff value necessary to achieve remission under the new criteria was analyzed by receiver operating characteristic (ROC) analysis. Data were analyzed using last observation carried forward. After 12 months of TCZ use, remission was achieved in 164 patients (57.5 %) by DAS28-ESR and 71 patients (24.9 %) under the new criteria for clinical trials. CRP levels scarcely affected remission rates, and the difference between remission rates defined by DAS28-ESR and by the new criteria was mainly due to patient global assessment (PGA). Improvement of PGA was inversely related to disease duration. ROC analysis revealed that the DAS28-ESR cutoff value necessary to predict remission under the new criteria for clinical trials was 1.54, with a sensitivity of 88.7 %, specificity of 85.5 %, positive predictive value of 67.0 %, and negative predictive value of 95.8 %. A DAS28-ESR cutoff value of 1.54 may be reasonable to predict achievement of remission under the new Boolean-based criteria for clinical trials in patients receiving TCZ.
Boolean; Criteria; DAS28-ESR; Remission; Tocilizumab
Schizophrenia is a multifactorial complex disease with a large impact on society. Many hypotheses have been proposed over the years to explain its causes, and genomics and functional genomic approaches may shed light on the reason behind these controversies and discrepancies. We give an overview of several approaches that have been used to identify the genetic causes and molecular phenotypes of the disease. We focus on a recent microarray analysis by Torkamani and colleagues on the evolution of regulatory networks in normal and schizophrenic brains. Combining the conclusion of that study with the prevalent hypotheses of schizophrenia, we suggest that the schizophrenic brain might resemble a juvenile brain.
With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal.
Rheumatoid arthritis; Remission
The most surprising feature of the inflammatory response in rheumatoid arthritis is not that it occurs but that it does not resolve. The persistence of the chronic inflammatory response in conjunction with ongoing joint destruction is an all too familiar finding in many patients with rheumatoid arthritis. Despite the use of effective anti-inflammatory agents and disease modifying drugs, a significant proportion of patients with rheumatoid arthritis continue to have resistant disease. Complete clinical remission is unusual for more than six months and a formal cure of the disease remains elusive. In this report we focus on how attempts to address the question of why rheumatoid arthritis persists have led to a different interpretation of the pathogenesis of rheumatoid disease; one in which alterations in stromal cells such as fibroblasts play an important role in the switch from resolving to persistent disease.
To describe use of the ACR/EULAR (AE) rheumatoid arthritis (RA) remission criteria in clinical practice.
We examined remission in the US Veterans Affairs RA (VARA) registry of 1,341 patients (91% men) with 9,700 visits and a community rheumatology practice (ARCK) of 1,168 patients (28% men) with 6,362 visits. We studied cross-sectional and cumulative probabilities, agreement among various remission criteria, and aspects of reliability using Boolean definitions and CDAI and SDAI methods proposed by AE.
By AE definition for community practice (swollen and tender joints ≤1, patient global ≤1), cross-sectional remission was 7.5% (6.4, 8.7) for ARCK and 8.9% (7.9, 9.9) for VARA. Cumulative or remission at any observation was 18.0% (ARCK) and 24.4% (VARA) over a mean of 2.2 years. Addition of ESR or CRP to criteria reduced remission to 5.0-6.2%, and use of CDAI/SDAI increased proportions to 6.9-10.1%. 1.8%-4.6% of patients met remission criteria at ≥2 visits. Agreement between criteria definitions was good by Kappa and Jaccard measures. Among patients in remission, the probability of a remission lasting 2 years was 6.0%-14.1%. Among all patients the probability of a remission lasting 2 years was <3%. Remission and examination results varied substantially among physicians by multilevel analyses.
Cross-sectional remission occurs at 5.0%-10.1%, with cumulative remission 2-3 times greater. Long-term remissions are rare. Problems with reliability and agreement limit criteria usefulness in the individual patient. However, the criteria can be an effective method for measuring clinical status and treatment effect in groups of patients in the community.
Rheumatoid arthritis; Remission; Reliability
Remission is an important goal of therapy in rheumatoid arthritis (RA), but data on duration of remission are lacking. Our objective was to describe the duration of remission in RA, assessed by different criteria.
We evaluated patients from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) not in remission at baseline with at least 2 years of follow-up. Remission was assessed according to the Disease Activity Score 28-C-reactive protein (DAS28-CRP4), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) scores, and the recently proposed American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) criteria for remission. Analyses were performed by using Kaplan-Meier survival curves.
We identified 871 subjects with ≥2 years of follow-up. Of these subjects, 394 were in remission at one or more time-points and not in remission at baseline, according to at least one of the following criteria: DAS28-CRP < 2.6 (n = 309), DAS28-CRP < 2.3 (n = 275), SDAI (n = 168), CDAI (n = 170), and 2010 ACR/EULAR (n = 158). The median age for the 394 subjects at entrance to BRASS was 56 years; median disease duration was 8 years; 81% were female patients; and 72% were seropositive. Survival analysis performed separately for each remission criterion demonstrated that < 50% of subjects remained in remission 1 year later. Median remission survival time was 1 year. Kaplan-Meier curves of the various remission criteria did not significantly differ (P = 0.29 according to the log-rank test).
This study shows that in clinical practice, a minority of RA patients are in sustained remission.
The primary purpose of this study was to evaluate the proportion of psoriatic arthritis (PsA) patients maintaining clinical remission after adalimumab (ADA) dose reduction compared with patients with rheumatoid arthritis. Secondary purposes include evaluating the proportion of PsA patients who achieve remission, the duration of remission after ADA dose reduction, time to relapse, psoriasis course, and the frequency of adverse events at the end of follow-up.
This was a single-center, prospective, follow-up, case-control study of 76 consecutive patients (35 females, 41 males; mean age 46 ± 10.2 years) who met the classification criteria for psoriatic arthritis and required anti-tumor necrosis factor therapy according to Group for Research and Assessment of Psoriasis and Psoriatic Arthritis recommendations. The 76 patients were compared with 55 patients (40 females, 15 males; mean age 50 ± 11.6 years) who satisfied the American College of Rheumatology criteria for rheumatoid arthritis and received the same treatment. Case patients and controls were recruited from January 2008 to December 2010. At baseline, PsA patients and controls received 40 mg of ADA every other week, usually with methotrexate (10 to 20 mg/weekly). In the presence of clinical remission, ADA dose was reduced to 40 mg every 4 weeks in both groups.
Fifty-three of the 76 (69.7%) PsA patients and 17 of the 55 (30.9%) rheumatoid arthritis (P < 0.019) controls achieved remission after a mean time of 5.1 ± 1.2 and 6.3 ± 1.6 months, respectively (P = nonsignificant). After halving the dose of ADA, 47 of the 53 (88.6%) PsA patients and three of the 17 (17.6%) controls maintained remission (P = 0.016) over a mean follow-up period of 28.9 ± 8.4 and 24.2 ± 6.4 months, respectively. No significant changes in Psoriatic Arthritis Severity Index scores were observed. The mean time to relapse was 8.3 ± 3.4 months in six case patients and 7.2 ± 4.2 in 14 controls (P = not significant). No serious adverse events occurred in either group.
Clinical remission is possible in a high percentage of patients with early PsA receiving ADA. Such remission is maintained in a high proportion of subjects after ADA dose halving, with relevant advantages in terms of patient compliance, drug-exposure risk, and economic burden.
psoriatic arthritis; anti-TNF; adalimumab; remission; dose reduction
Disease remission has become a feasible goal for most rheumatoid arthritis (RA) patients; however, patient-reported symptoms, such as pain, may persist despite remission. We assessed the prevalence of pain in RA patients in remission according to the Disease Activity Score (DAS28-CRP4) and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria.
Data were analyzed from RA patients in the Brigham Rheumatoid Arthritis Sequential Study with data at baseline and 1 year. DAS28 remission was defined as DAS28-CRP4 <2.6. The ACR/EULAR remission criteria included (a) one or more swollen joints, (b) one or more tender joints, (c) C-reactive protein ≤1 mg/dl, and (d) patient global assessment score ≤1. Pain severity was measured by using the pain score from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). The associations between baseline clinical predictors and MDHAQ pain at baseline and 1 year were assessed by using multivariable linear regression.
Among the 865 patients with data at baseline and 1 year, 157 (18.2%) met DAS28-CRP4 remission criteria at both time points. Thirty-seven (4.3%) met the ACR/EULAR remission criteria at baseline and 1 year. The prevalence of clinically significant pain (MDHAQ pain ≥4) at baseline ranged from 11.9% among patients meeting DAS28-CRP4 remission criteria to none among patients meeting ACR/EULAR remission criteria. Patient global assessment, MDHAQ function, MDHAQ fatigue, MDHAQ sleep, and arthritis self-efficacy were significantly associated with MDHAQ pain in cross-sectional (P ≤ 0.0005) and longitudinal analyses (P ≤ 0.03). Low swollen-joint counts were associated with high MDHAQ pain in longitudinal analyses (P = 0.02) but not cross-sectional analyses. Other measures of inflammatory disease activity and joint damage were not significantly associated with MDHAQ pain at baseline or at 1 year.
Clinically significant pain continues among a substantial proportion of patients in DAS28 remission but not among those in ACR/EULAR remission. Among patients in DAS28 remission, patient global assessment, disability, fatigue, sleep problems, and self-efficacy are strongly associated with pain severity at baseline and 1 year, whereas inflammatory disease activity and joint damage are not significantly associated with elevated pain severity at either baseline or 1 year.
Individuals who have developed a clinical dependence on drugs and/or alcohol often report that they sought help because they were “sick and tired of being sick and tired.” Quality of life (QOL) remains the missing measurement in the addictions arena. The few studies conducted to date show that QOL is typically poor during active addiction and improves as a function of remission. An intriguing question bears on the role of quality of life in subsequent remission status. Reasoning that higher life satisfaction may `increase the price' of future use and thus enhance the likelihood of sustained remission, this exploratory study tests the hypotheses that quality of life satisfaction prospectively predicts sustained remission, and that motivational constructs mediate the association. Inner city residents (N = 289, 53.6% male, mean age 43) remitting from chronic and severe histories of dependence to crack and/or heroin were interviewed three times at yearly interval beginning in April 2003. Logistic regression findings generally support our hypotheses: Controlling for other relevant variables, baseline life satisfaction predicted remission status one and two years later and the association was partially mediated by motivation (commitment to abstinence) although the indirect effect did not reach statistical significance. Findings underline the importance of examining the role of quality of life satisfaction in remission processes. Limitations of this exploratory study are discussed including the use of a single item global life satisfaction rating; suggestions for future studies are discussed including the need to embrace QOL as a bona fide clinical outcome and to use comprehensive standardized QOL measures that speak to individual dimensions of functioning. Implications are noted, especially the need for the addiction field to continue moving away from the pathology-focused model of care toward a broader model that embraces multiple dimensions of positive health as a key outcomes.
Quality of life; remission; recovery; motivation; addiction; processes
Remission was a rare event, even in the most advanced rheumatology clinics, until recent times. However, in the early 1990s, it was chosen as the treatment goal and the primary outcome measure for the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial, which can be considered the beginning of remission's way to rheumatology. In addition to remission in patients with rheumatoid arthritis, remission in patients with psoriatic arthritis is now being studied, although remission criteria for psoriatic arthritis have yet to be defined. Better treatment results with more active treatment strategies and availability of biologic agents motivate rheumatologists to monitor their patients as part of usual rheumatology care.
To assess the radiological damage progression in patients with recent rheumatoid arthritis in sustained remission.
A cohort of 191 patients with active early (<1 year) rheumatoid arthritis was prospectively assessed at baseline, 3 and 5 years by the Disease Activity Score (DAS) and the Sharp–van der Heijde Score (SHS) for radiographic damage. Patients in remission (DAS<1.6) at the 3‐year and 5‐year time points were compared with patients with a persistently active rheumatoid arthritis by Wilcoxon's signed rank test.
57 patients died, were lost to follow‐up or had incomplete data; 30 (15.7% of those who completed) patients were in remission at 3 and 5 years. The SHS in these two groups was not significantly different at baseline (p = 0.15), but was lower in the remission group at 5 years (p = 0.0047). The median (IQR) radiographic score increased from 0.5 (0–7) at baseline to 2.5 (0–14) after 5 years for the remission group (p = 0.18) and from 2 (0–7) to 13 (3–29) in the group with active rheumatoid arthritis (p<0.001). 5 (16.7%) patients in remission had relevant progression of radiographic damage (ie, progression >4.1 points) and 6 (20%) presented new erosions in a previously unaffected joint between the third and the fifth years.
Patients with early rheumatoid arthritis in sustained remission did not present statistically significant radiographic degradation at the group level; nevertheless, 16.7% of these patients did present degradation. Absence of progression should be part of the remission definition in rheumatoid arthritis.
To compare 28 joint disease activity score (DAS28) remission with comprehensive joint count DAS remission in rheumatoid arthritis.
620 actually measured paired observations of DAS28 and DAS were analysed in 155 patients. Discordant observations (either DAS or DAS28 below remission cut off level: 1.6 for DAS and 2.6 for DAS28) and concordant observations (both DAS and DAS28 below their remission cut off level) were analysed separately.
91 of 620 paired DAS observations (15%) were discordant; 87 (in 53 patients) comprised observations in which the DAS28 remission criterion, but not the DAS remission criterion, was met. The reverse was found in only four observations, which were therefore omitted. With the original DAS as standard, DAS28 sensitivity was 95% and specificity 84%. Probability plots showed a swollen joint count >0 in 75% of discordant pairs v 48% of concordant pairs. The same was found for total joint count (TJC >0 in 90% v 40%; median TJC, 0 v 6) and patient global assessment, but not for ESR. Individual joint analysis showed that 51% of discordant v 18% of concordant observations (p<0.0005) had involvement of lower extremity joints that are not included in the DAS28.
DAS remission is more conservative than DAS28 remission. Activity (tenderness and swelling) in joints not included in the reduced joint counts (ankles, feet) mainly account for the discrepancy between the two assessments. DAS28 remission at a cut off level of 2.6 has insufficient construct validity and should be used with caution in clinical practice and clinical trials.
remission; disease activity score; probability plot
With remission in rheumatoid arthritis (RA) an increasingly attainable goal, there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome in clinical trials.
A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism and the Outcome Measures in Rheumatology Initiative (OMERACT) met to guide the process and review prespecified analyses from clinical trials of patients with RA. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures to define remission including at least joint counts and an acute phase reactant. Members were surveyed to select the level of each core set measure consistent with remission. Candidate definitions of remission were tested including those that constituted a number of individual measures in remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient reported outcomes and the ability of candidate measures to predict later good x-ray and functional outcomes.
Survey results for the definition of remission pointed to indexes at published thresholds and to a count of core set measures with each measure scored as 1 or less (e.g. tender and swollen joint counts, CRP and global assessments on 0-10 scale). Analyses suggested the need to include a patient reported measure. Examination of 2 year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good x-ray and functional outcomes, although DAS28 based measures of remission did not predict good radiographic outcomes as well as did the other candidate definitions. Given these and other considerations, we propose that a patient be defined as in remission based on one of two definitions : 1: When their scores on the following measures are all <1: tender joint count, swollen joint count, CRP (in mg/dL) and patient global assessment (0-10 scale), OR 2: when their score on the SDAI is < 3.3.
We propose two new definitions of remission both of which can be uniformly applied and widely used in RA clinical trials. We recommend that one of these be selected in each trial as an outcome and that the results on both be reported in each trial.
Objective: To determine prognostic factors for remission in early rheumatoid arthritis.
Methods: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained.
Results: 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score.
Conclusions: Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.
With regard to rheumatoid arthritis, remission as currently used in the literature can have two meanings: either a state with persistent absence of clinical and radiological signs of disease activity without being treated for a specific time period, or it may point to a disease state with minimal disease activity during antirheumatic treatment. A risk factor for the first is absence of autoantibodies, with the anti-CCP-antibodies as best predictors, whereas risk factors for achieving a drug-induced state of minimal disease activity are not well defined. These definitions of remission refer to different disease states; therefore, we propose that the term remission is reserved for patients that are not treated with antirheumatic drugs.
Polyarticular juvenile idiopathic arthritis (JIA) is a category of JIA where multiple joints are affected by chronic inflammation, and where serious and lasting damage to joints is the expected natural history in untreated disease. There is evidence of response to disease-modifying antirheumatic and biologic drugs, but little evidence of permanent remission from any of the existing therapeutic trials. The TREAT trial by Wallace et al., recently published in Arthritis and Rheumatism, used a collaborative multicenter approach to studying early aggressive treatment of polyarticular JIA in an attempt to achieve full clinical inactive disease after 6 months of treatment. The study's main finding that the earlier in the disease course that treatment is started, the better the chance of disease control, has provided evidence that there is a 'window of opportunity' for treating JIA as there is in adult rheumatoid arthritis (RA). The study provides both a platform and an impetus for concentrating future treatment trials on early rather than established disease and investigating a standard of starting treatment within 10 to 12 weeks.
Childhood arthritis; polyarticular juvenile arthritis; treatment
Pregnancy frequently has a beneficial effect on the autoimmune disease Rheumatoid Arthritis, ranging from improvement in clinical symptoms to complete remission. Despite decades of study, a mechanistic explanation remains elusive. Here, we demonstrate that an analogous pregnancy-induced remission can be observed in a mouse model of arthritis. We demonstrate that during pregnancy mice are protected from collagen-induced arthritis, but are still capable of launching normal immune responses to influenza infections. We examine the role of regulatory T (TR) cells in this beneficial effect. TR cells are essential for many aspects of immune tolerance, including the suppression of autoimmune responses. Remarkably, transfer of regulatory T cells from pregnant ‘protected’ mice was sufficient to confer protection to non-pregnant mice. These results suggest that regulatory T cells are responsible for the pregnancy-induced amelioration of arthritis.
► Pregnancy-induced protection from RA is not due to systemic immunosuppression. ► The effect can be studied in Collagen-Induced Arthritis, a mouse model of human RA. ► Protection can be transferred from pregnant-protected to control mice using TR cells. ► The pregnancy-induced suppression of RA by TR cells is antigen-specific.
Rheumatoid arthritis; Pregnancy; Regulatory T cells; Mouse model; RA, rheumatoid arthritis; TR, regulatory T cells; CIA, collagen-induced arthritis; PAMPs, pathogen-associated molecular patterns
Fourteen patients with severe rheumatoid arthritis (RA) were given 27 courses of methylprednisolone intravenously, each of 3 infusions of 1 g on alternate days. After 7 days there was marked improvement in clinical state and most laboratory tests; levels of ESR and 4 serum acute-phase proteins, C3, C, IgG, and IgA, fell significantly. Serum IgM and rheumatoid factor titre were unchanged. 125I C1q binding fell in all instances where it was initially raised. Clinical remission lasted a mean of 10 weeks. Serum C-reactive protein (CRP) fell to less than 30 mg/l after all courses except one within 7 days and rose above this figure after a mean of 7 weeks. The ESR fell below 30 mm/h within seven days in 17 courses and remained below this value for a mean of 7 weeks. Three patients had clinical remissions, with serum CRP less than 30 mg/l and ESR less than 30 mm/h, lasting more than 42 weeks.