Sustained rheumatoid arthritis remission is uncommon in clinical practice

Introduction

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.

Methods

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.

Results

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).

Conclusions

This study shows that in clinical practice, a minority of RA patients are in sustained remission.     

Physical function continues to improve when clinical remission is sustained in rheumatoid arthritis patients

IntroductionTo investigate the course of functional status assessed by health assessment questionnaire (HAQ) in rheumatoid arthritis (RA) patients with sustained clinical remission (REM).MethodsIn recent RA clinical trials, we identified patients with subsequent visits of ≥24 weeks in clinical REM according to the disease activity score using 28-joint counts including C-reactive protein (DAS28) (≤2.6), or simplified disease activity index (SDAI) (≤3.3). Area under the curve (AUC) and mean HAQ scores throughout the time in sustained REM were compared using t test, analyses of variance (ANOVA) and adjusted general linear modeling (GLM) with repeated measures. In Cox regression analyses, the time to regain full physical function was modeled. Sensitivity analyses were performed in patients of sustained SDAI low disease activity (LDA; SDAI ≤11).ResultsA total of 610 out of 4364 patients achieved sustained DAS28 REM (14 %) and 252 SDAI REM (5.8 %). ANOVA testing for linear trend showed significant decrease of mean HAQ from week 0 (start of REM) to week 24, regardless of REM criteria used. AUC of HAQ throughout 24 weeks of REM was higher in DAS28 compared to SDAI REM (p ≤0.01). GLM adjusting for covariates showed significant decrease of monthly HAQ scores from week 0 to 24 (DAS28: 0.276, 0.243, 0.229, 0.222, 0.219, 0.209 to 0.199; p = 0.0001; SDAI: 0.147, 0.142, 0.149, 0.129, 0.123, 0.117 to 0.114; p = 0.029). Similarly, a decrease of HAQ over time was found in patients of sustained SDAI LDA. In DAS28 REM, the chance of regaining full physical function was higher for female (hazard ratio HR [95 % confidence interval]: 1.41 [1.13–1.76]) and early RA patients (disease duration ≤2 years: HR 1.29 [1.01–1.65]); in SDAI REM no significant differences were found.ConclusionsPhysical function continues to improve if the target of REM or LDA is sustained. The stringency of the remission criteria determines achievement of the best possible functional improvement.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0719-x) contains supplementary material, which is available to authorized users.     

Forefoot disease activity in rheumatoid arthritis patients in remission: results of a cohort study

Introduction  

The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion.     

Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis - a systematic review of the literature

Introduction

Ultrasonography (US) might have an added value to clinical examination in diagnosing early rheumatoid arthritis (RA) and assessing remission of RA. We aimed to clarify the added value of US in RA in these situations performing a systematic review.

Methods

A systematic literature search was performed for RA, US, diagnosis and remission. Methodological quality was assessed; the wide variability in the design of studies prohibited pooling of results.

Results

Six papers on the added value of US diagnosing early RA were found, in which at least bilateral metacarpophalangeal (MCP), wrists and metatarsophalangeal (MTP) joints were scanned. Compared to clinical examination, US was superior with regard to detecting synovitis and predicting progression to persistent arthritis or RA. Eleven papers on assessing remission were identified, in which at least the wrist and the MCP joints of the dominant hand were scanned. Often US detected inflammation in patients clinically in remission, irrespective of the remission criteria used. Power Doppler signs of synovitis predicted X-ray progression and future flare in patients clinically in remission.

Conclusions

US appears to have added value to clinical examination for diagnosing of RA when scanning at least MCP, wrist and MTP joints, and, when evaluating remission of RA, scanning at least wrist and MCP joints of the dominant hand. For both purposes primarily power Doppler US might be used since its results are less equivocal than those of greyscale US.     

Predicting joint damage in rheumatoid arthritis using MRI scanning

Predicting prognosis in the patient with newly diagnosed rheumatoid arthritis is of key importance so that high-cost therapies can be tailored to the needs of the individual. In a recent issue of Arthritis Research and Therapy, the prognostic significance of MRI changes at the forefoot has been studied. While progression to radiographic erosion occurred rarely in this group of patients exposed to potent disease-suppressing therapies, including TNF inhibitors, MRI bone edema, representing osteitis, has been further implicated as a forerunner to bone erosion. Early MRI scans of the forefoot were helpful in defining those with the potential to progress as well as those in a good prognosis category.     

Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.     

Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis

IntroductionClinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.MethodsThe Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2–8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.ResultsJE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.ConclusionsExisting JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00195663","term_id":"NCT00195663"}}NCT00195663. Registered 13 September 2005.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0626-1) contains supplementary material, which is available to authorized users.     

Arthrosonography in the diagnosis of rheumatoid arthritis of the knee joint

The paper presents the capacities of echography in the estimation of the activity of rheumatoid gonitis. A study of knee joints in 126 patients with rheumatoid arthritis has provided the basic ultrasound criteria that are characteristic for the first, second, and third degrees of its progression, which include the pattern of proliferative changes in the synovium, the qualitative and quantitative assessments of intraarticular exudate and its viscosity. The capacities of X-ray study and MRI in the detection of the progression of rheumatoid arthritis are discussed. An algorithm of knee joint radiation study is proposed for patients with rheumatoid arthritis.     

Declining needs for total joint replacements for rheumatoid arthritis

This millennium brings new views to rheumatology. Total joint replacement surgery is needed less often as active treatment strategies combined with availability of new medications has led to more effective rheumatoid arthritis control. This was beautifully shown in a recent issue of Arthritis Research & Therapy by a Swedish study that uses data from national registers and compares incidence rates for total hip and knee arthroplasties before and after the establishment of biologic agents use for rheumatoid arthritis     

The role of interleukin-17 in mediating joint destruction in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, persistent inflammatory joint disease with systemic involvement that affects about 1% of the world’s population, that ultimately leads to the progressive destruction of joint. Effective medical treatment for joint destruction in RA is lacking because the knowledge about molecular mechanisms leading to joint destruction are incompletely understood. It has been confirmed that cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including RA. Recently, IL-17 was identified, which production by Th17 cells. IL-17 has proinflammatory properties and may promote bone and joint damage through induction of matrix metalloproteinases and osteoclasts. In mice, intra-articular injection of IL-17 into the knee joint results in joint inflammation and damage. In addition, it has been shown that blocking IL-17/IL-17R signaling is effective in the control of rheumatoid arthritis symptoms and in the prevention of joint destruction. In this article, we will briefly discuss the biological features of IL-17/IL-17R and summarize recent advances on the role of IL-17/IL-17R in the pathogenesis and treatment of joint destruction in RA.     

Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis

AIM: To investigate whether blood serotonin (5-hydroxytryptamine) (5-HT) modulates musculoskeletal pain differently in seropositive and seronegative rheumatoid arthritis (RA). METHODS: Patients with temporomandibular joint (TMJ) involvement of seropositive RA (33 patients) or seronegative RA (28 patients) and 26 healthy individuals were included. TMJ pain, general musculoskeletal pain, plasma and serum 5-HT, acute phase reactants and thrombocyte count were investigated. RESULTS: The patients with seropositive RA had higher serum (median = 1130 nmol/l) and plasma (55 nmol/l) levels of 5-HT than the healthy individuals (704 nmol/l, p = 0.044 and 23 nmol/l, p < 0.001, respectively), and higher plasma levels of 5-HT than the seronegative patients (14 nmol/l, p < 0.001). There was no significant correlation between serum and plasma levels of 5-HT in any group. In the seropositive RA patients, positive correlations were found between serum levels of 5-HT and the number of painful mandibular movements (r(s) = 0.36, n = 33, p = 0.042), as well as pain on maximum mouth opening (r(s) = 0.41, n = 24, p = 0.047) and tenderness to digital palpation (r(s) = 0.49, n = 33, p = 0.003). In the healthy individuals, there was a negative correlation between plasma level of 5-HT and the TMJ pressure pain threshold (r(s) = -0.47, n = 20, p = 0.037). CONCLUSION: Peripheral serotonergic pain mechanisms seem to be activated by blood 5-HT in patients with seropositive RA, in contrast to seronegative patients.     

Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study

Introduction  

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.     

Plasma lipidomic profiling in patients with rheumatoid arthritis

Introduction

Rheumatoid arthritis (RA) is linked to increased cardiovascular morbidity and mortality, not completely explained by traditional risk factors. Importantly, the increased risk occurs despite lower levels of total and low-density lipoprotein cholesterol. Whilst systemic inflammation may be a factor, it is possible that changes in individual lipid species contribute to the increased cardiovascular risk.

Objectives

In the present study, we characterized plasma lipidomic profiles in patients with RA in comparison with healthy controls.

Methods

Patients with RA (n = 32) and age- and gender-matched healthy volunteers (n = 84) were recruited. Fasting plasma lipid profiles were measured using electrospray-ionisation tandem mass spectrometry. 24 lipid classes and subclasses were measured.

Results

Patients with RA had normal total, low-density lipoprotein and high-density lipoprotein cholesterol, but higher triglycerides than controls. Five lipid classes (dihydroceramides, alkylphosphatidylethanolamine, alkenylphosphatidylethanolamine, lysophosphatidylinositol, phosphatidylserine) differed between patients with RA and controls. Then we measured 36 lipid species within these 5 classes and found that 11 lipid species were different between patients with RA and controls. Three lipid classes (dihydroceramides, lysophosphatidylinositol, phosphatidylserine) and 10 lipid species remained significantly associated with RA after adjusting for age, sex, body mass index, current smoking, systolic blood pressure and anti-hypertensive treatment in a binary logistic regression model.

Conclusion

This study has identified lipid alterations in RA. These alterations of lipids warrant further investigation as they may be associated with accelerated atherosclerosis and joint inflammation in patient with RA.