Activity In Early Rheumatoid Arthritis Research Articles

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort.

Background: Long-chain omega-3 and omega-6 fatty acids (n-3, n-6 FAs) may modulate inflammation and affect the risk of developing rheumatoid arthritis (RA). However, whether n-3/n-6 FA status affects RA after disease onset is unknown. This study aimed to assess whether FA profiles are independently associated with disease activity in a large prospective cohort of patients with early RA. Methods: Baseline serum FAs were quantified in 669 patients in the ESPOIR cohort. Principal component analysis identified three serum FA patterns that were rich in n-7–9, n-3 and n-6 FAs (patterns ω7–9, ω3 and ω6), respectively. The association of pattern tertiles with baseline variables and 6-month disease activity was tested using multivariable logistic regression. Results: Pattern ω3 was associated with low baseline and pattern ω6 with high baseline C-reactive protein level and disease activity. Both patterns ω3 and ω6 were associated with reduced odds of active disease after 6 months of follow-up (pattern ω3: odds ratio, tertile three vs. one, 0.49 [95% CI 0.25 to 0.97] and pattern ω6: 0.51 [0.28 to 0.95]; p = 0.04 and 0.03, respectively). Conclusions: In a cohort of early RA patients, a serum lipid profile rich in n-3 FAs was independently associated with persistently reduced disease activity between baseline and 6-month follow-up. An n-6 FA profile was also associated with lower 6-month disease activity.

OP0059 PROFOUND ANTICOAGULANT EFFECTS OF INITIAL ANTIRHEUMATIC TREATMENTS IN EARLY RHEUMATOID ARTHRITIS PATIENTS: A NORD-STAR SPIN-OFF STUDY

BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk of venous thromboembolism. Thus far, there have not been any comparative studies investigating the effects of initial antirheumatic treatments in (very) early RA patients.ObjectivesTo assess the effects of different initial treatments on hemostatic parameters in patients with early RA.MethodsNORD-STAR is an international, multicentre, open-label, assessor-blinded, phase 4 study where patients with newly diagnosed RA started methotrexate (MTX) and were randomised 1:1:1:1 to a) conventional treatment (either prednisolone tapered to 5mg/day, or sulfasalazine combined with hydroxychloroquine and intra-articular corticosteroids), b) certolizumab pegol, c) abatacept, d) tocilizumab1. This study is a spin-off from the main NORD-STAR study extensively investigating hemostatic system in 24 per protocol consecutive Dutch participants at baseline, 12 weeks and 24 weeks after the start of the treatment. Statistical analysis was done using paired samples t-test in SPSS version 28.ResultsThe mean age of investigated patients was 51.8 (± 12.7) years and 58.3% were female. At baseline patients had an average DAS28 score of 4.6 (± 0.9) and had elevated levels of investigated coagulation biomarkers: Factor 1 + 2, fibrinogen, D-dimer and parameters of the two global hemostatic assays, i.e. endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). These biomarkers decreased significantly at 12 and 24 weeks in patients in all groups (Table 1). Overall fibrinolytic potential (OFP) was decreased and clot lysis time (CLT) was prolonged at baseline, demonstrating impaired fibrinolytic activity in early RA. The reduction of coagulation parameters was significantly higher in biological treatment arms in comparison to the standard MTX treatment arm. In addition, tocilizumab was more effective compared to certolizumab and abatacept, (Figure 1), which was expected considering the direct inhibitory effect of this drug on the IL-6 synthesis and consequently the coagulation activation as well. After 24 weeks of treatment with methotrexate and tocilizumab, the average fibrinogen of patients was reduced by 63% vs 31% and 36% in the certolizumab and abatacept groups, respectively. The changes in DAS-28 and the changes in fibrinogen had a correlation of 0.385 which did not reach statistical significance.Table 1.Measurements are marked with * if p<0.05, ** if p<0.01 and *** if p<0.001BaselineW12W24Factor 1 + 2 (pmol/L)270.25 (149.4)190.36 (108.6)**179.52 (85.3)***Fibrinogen (g/L)4.64 (1.5)3.61 (1.6)**2.63 (1.2)***D-dimer (mg/L)2.17 (3.0)0.33 (0.23)**0.29 (0.2)**OHP (Abs-sum)157.38 (64.9)120.62 (68.7)*100.49 (53.8)***OCP (Abs-sum)369.52 (58.8)305.04 (101.7)*275.91 (83.1)***OFP (%)57.97 (13.1)63.20 (12.7)*65.25 (11.4)***Lag time (s)304.5 (71.1)306.8 (71.8)312.7 (65.4)Slope0.07 (0.02)0.066 (0.03)0.094 (0.12)Max Abs1.17 (0.3)1.00 (0.4)*0.91 (0.3)**CLT (s)1405 (356)1317 (377)1231 (320)**ETP (nM*min)1480 (471)1395 (395)*1337 (429)*Peak (nM)231 (78)223 (68)223 (74)Lagtime (min)4.06 (2.1)3.28 (1.2)**2.87 (1.0)***ttPeak (min)7.40 (2.2)6.61 (1.5)*6.13 (1.4)**Figure 1.ConclusionOur results indicate an enhanced coagulation and fibrinolytic impairment in newly diagnosed RA patients. Effective antirheumatic treatments reduce this hemostatic imbalance, with significantly more pronounced effects of biologic drugs compared to conventional (MTX+glucocorticoids) treatment.

Serum Tumor Necrosis Factor-Alpha as a Competent Biomarker for Evaluation of Disease Activity in Early Rheumatoid Arthritis.

AimThe cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pathophysiology of rheumatoid arthritis (RA). The goal of this study was to evaluate the role of serum TNF-α as a competent biomarker of disease activity in RA and to assess the correlation of serum TNF-α with DAS28-ESR (disease activity score-erythrocyte sedimentation rate in 28 joints) and other markers expressed in serum of RA patients.MethodologyThe study was conducted from May 2020 to October 2020 after approval from the Ethical Review Committee of Ziauddin University. This cross-sectional study included 90 diagnosed cases of RA from 30 to 65 years with the complaint of arthralgia. Patients from the rheumatology clinic were enrolled in the study by a non-probability consecutive sampling technique. Informed consent was taken from each patient and they were assessed through a set of questions based upon disability in the performance of daily activities due to RA. Evaluation of serum levels of anti-cyclic citrullinated peptide (ACCP), rheumatoid factor (RF), erythrocyte sedimentation rate, and TNF-α were done by enzyme-linked immunosorbent assay (ELISA). Patients were segregated into groups based upon DAS28-ESR with erythrocyte sedimentation rate as an inflammatory marker. The Kruskal Wallis test was applied for the comparison of different variables in these groups. Spearman correlation was applied for the association between different variables. Multiple variable analysis was performed to assess the predictability of disease activity by serum markers included in the study.ResultsThe results of our study disclosed a significant difference in ACCP, TNF-α, tender joint count of 28 joints (TJ-28), swollen joint count of 28 joints (SJ-28), and health assessment questionnaire-disability index (HAQ-DI) in disease activity groups. A significant correlation of serum TNF-α with DAS28-ESR in RA patients was observed.ConclusionThis study illustrated a significant correlation of serum TNF-α with DAS28-ESR in RA patients. We found that expression of serum TNF-α may intensify the inflammatory activity in early RA, therefore, RA patients must be screened for this cytokine to monitor that disease activity could be useful for patients undergoing anti-TNF therapy.

Association of Leptin Levels and Disease Activity in Patients with Early Rheumatoid Arthritis

Previous studies have reported a link between metabolic parameters and disease activity in rheumatoid arthritis (RA), although the evidence is limited in early RA. We aimed to investigate the relationship between disease activity and adipocytokine levels in subjects with early RA. Forty-seven patients with early RA (symptom duration ≤12 months) were enrolled. Disease activity was determined by DAS28-CRP. Patients were treated with DMARDs according to the EULAR recommendations. Subjects were tested before and five months after treatment. Early RA patients with high disease activity (DAS28-CRP > 4.9) had greater BMI (31.2 ± 6.8 kg/m2 vs. 26.7 ± 4.1 kg/m2; p = 0.006) and higher leptin levels (14.62 ± 15.60 ng/mL vs. 7.82 ± 8.00 ng/mL; p = 0.048). Levels of other adipocytokines were not significantly different. Leptin levels were similar in subjects with mild/moderate disease activity and controls. DAS28-CRP was correlated with leptin (r = 0.303, p = 0.039). Leptin levels decreased significantly after treatment (from 10.86 ± 12.34 ng/mL to 9.22 ± 9.29 ng/mL; p = 0.047) along with insulin levels (from 13.68 ± 21.90 mU/L to 7.09 ± 4.72 mU/L; p = 0.010) and HOMA-IR (from 4.39 ± 9.53 to 1.70 ± 1.38; p = 0.012). HDL cholesterol levels increased (from 41 ± 10 mg/dL48 ± 10 mg/dL; p <0.001). Leptin levels were associated with disease activity in patients with early RA and these levels decreased after treatment with DMARDs. Further research is needed to elicit leptin's role to regulate disease activity in early RA.

Serum levels of the soluble urokinase plasminogen activator receptor (suPAR) correlates with disease activity in early rheumatoid arthritis and reflects joint damage over time

Soluble urokinase plasminogen activator receptor (suPAR) is intensively studied as a biomarker of inflammation and disease outcome in various diseases. In rheumatoid arthritis (RA), suPAR have shown an association with inflammation and swollen joints, but data on suPAR in relation to early disease course and disease progression are lacking. This study investigates the potential of suPAR to predict or reflect disease outcome in early RA. Serum suPAR was measured by enzyme-linked immunosorbent assay at disease onset and after 3 and 36 months in 252 patients from a Swedish prospective observational early RA cohort. Levels and changes of suPAR were analyzed in relation to the 28-joint disease activity score (DAS28) and joint damage according to the Larsen score at inclusion and during follow-up. 100 healthy blood donors served as controls. Circulating levels of suPAR were higher in RA patients at all time points as compared to healthy controls. Baseline suPAR was significantly associated with baseline disease activity whereas suPAR levels at 36 months were associated with joint damage at 36 months. No predictive value of suPAR levels or changes in suPAR levels over time were found. In conclusion, suPAR levels associate with disease activity in early untreated RA and reflects joint damage at later stages. Increased suPAR in established RA could indicate patients in need of frequent monitoring of joint status, irrespective of disease activity. In the view of suPAR as a rapidly emerging biomarker, it is important to be aware of its ability to reflect both inflammation and subsequent damage.

Anti-cyclic citrullinated peptide antibodies are associated with radiographic damage but not disease activity in early rheumatoid arthritis diagnosed in 2006–2011

Objective: The discovery of anti-citrullinated protein antibodies (ACPAs) and the introduction of new therapeutic options have had profound impacts on early rheumatoid arthritis (RA) care. Since ACPA status, most widely assessed as reactivity to cyclic citrullinated peptides (CCPs), influences treatment decisions in early RA, we aimed to determine whether anti-CCP remains a predictor of disease activity and radiographic joint damage in more recent ‘real-world’ early RA. Method: Two observational early RA cohorts from Sweden enrolled patients in 1996–1999 (TIRA-1, n = 239) and 2006–2009 (TIRA-2, n = 444). Clinical and radiographic data and ongoing treatment were prospectively collected up to 3 years. Two other cohorts served as confirmation cohorts (TRAM-1, with enrolment 1996–2000, n = 249; and TRAM-2, 2006–2011, n = 528). Baseline anti-CCP status was related to disease activity, pharmacotherapy, and radiographic joint damage according to Larsen score. Results: In the TIRA-1 cohort, anti-CCP-positive patients had significantly higher 28-joint Disease Activity Score, swollen joint count, C-reactive protein level, and erythrocyte sedimentation rate during follow-up compared with anti-CCP-negative patients. In TIRA-2, no such differences were found, but baseline anti-CCP positivity was associated with higher 3 year Larsen score (5.4 vs 3.5, p = 0.039). In TRAM-2, anti-CCP also predicted radiographic damage (8.9 vs 6.7, p = 0.027), with no significant differences in disease activity. Conclusion: In the early RA cohorts recruiting patients in 2006–2011, baseline anti-CCP positivity was not associated with disease activity over time, but was associated with increased radiographic damage at follow-up. Hence, close radiographic monitoring is warranted in early anti-CCP-positive RA regardless of disease activity.

Presence of anti-citrullinated protein antibodies and costs and disease activity in early rheumatoid arthritis - a 3-year follow-up

Objective: To analyse healthcare utilization, loss of productivity, and disease activity in relation to presence of anti-citrullinated protein antibodies (ACPAs). Method: In total, 447 ACPA-positive and 224 ACPA-negative patients from two early rheumatoid arthritis cohorts, recruited 1996–1998 (cohort 1) and 2006–2009 (cohort 2), were followed during 3 years. Data on disease activity were collected, and patients reported healthcare utilization and days lost from work. Disease activity, healthcare costs, and loss of productivity were compared between ACPA groups. Linear regression was performed, controlling for confounders. Results: Healthcare costs did not differ significantly by ACPA status (EUR 3214 for vs EUR 2174 for ACPA-positive vs ACPA-negative patients in cohort 1, ns; EUR 4150 vs EUR 3820 in cohort 2, ns). Corresponding values for loss of productivity were EUR 9148 vs EUR 7916 (ns) and EUR 5857 vs EUR 5995 (ns). Total prescription of traditional disease-modifying anti-rheumatic drugs was higher in cohort 2 than in cohort 1. Methotrexate prescription was higher in ACPA-positive patients, but biologics did not differ significantly between ACPA groups. Disease activity was significantly more improved in cohort 2, but there was no difference in achieving remission in relation to ACPA status. In cohort 1, 25% of ACPA-positive patients were in remission vs 31% of ACPA-negative (ns) and in cohort 2, 55% vs 60% (ns). Conclusions: With increasing drug treatment for both ACPA-positive and ACPA-negative patients, outcome in ACPA-positive was no more severe than in ACPA-negative patients. Healthcare costs and loss of productivity were similar in the two groups.

Promoting engagement in physical activity in early rheumatoid arthritis: A proof-of-concept intervention study.

The aim of this study is to test the feasibility and acceptability of promoting engagement in physical activity in early rheumatoid arthritis (PEPA-RA) to inform a future trial. A 'proof of concept' study was carried out. This study was conducted in community hospitals delivered by musculoskeletal primary care physiotherapists. Participants were 12 adults with rheumatoid arthritis (RA) diagnosed 6-24 months previously (nine females, three males; mean age 58 years, range 23-79). The intervention consisted of five sessions, that is, four group sessions and one individual session facilitated by a physiotherapist over 12 weeks including patient education and support for behaviour change as well as supervised practical exercise. The main outcomes were attendance, completion of outcome measures, adverse events, and participant and physiotherapist feedback views relating to the intervention. Overall attendance was 85%, with sessions missed due to illness or RA flare. Outcome measure completion ranged from 83% to 100%. There were no clinically meaningful changes in pain or function at 12 weeks, but mean 6-min walk distance improved from 394 to 440 m. No serious adverse events were reported, and participants were generally positive about the intervention. Suggested minor modifications for the group sessions included venue accessibility and ensuring that physical activity time was protected. Several participants indicated that they would have liked to receive the intervention earlier following diagnosis. PEPA-RA and the outcomes appear feasible and acceptable. Overall, small beneficial effects were noted at 12 weeks for most outcomes. Challenges to recruitment resulted in a smaller than anticipated sample size, and the majority of participants were active at baseline indicating that future recruitment needs to target less active individuals.

THU0093 EARLY REMISSION IS ASSOCIATED WITH LOWER FATIGUE LEVELS ON THE LONG TERM IN PATIENTS WITH RECENT ONSET RHEUMATOID ARTHRITIS

Background:Fatigue is mentioned as a symptom with high impact in many patients with Rheumatoid Arthritis (RA) and this symptom remains difficult to be managed by both the patient and the physician.Objectives:To investigate if rapid suppression of disease activity in early RA could impact fatigue complaints in the long run.Methods:For this study, we included patients from the 2-year pragmatic investigator-initiated Care in Early Rheumatoid Arthritis (CareRA) trial. Most patients were treated intensively, with different combinations of csDMARDs and glucocorticoid remission induction schemes, except one group without classic markers of poor prognosis that was treated with MTX weekly in monotherapy. Patients were followed up at least every 3 months, with more mandatory visits in the first 6 months of treatment. Clinical parameters including DAS28 components were registered at every visit. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-reported instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to no motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Only patients with a filled-out MFI at baseline and available DAS28CRP at week 16 were included in this study.Patients were divided in 2 groups based on their response, defined as achieving or not achieving DAS28CRP remission (&lt;2.6) at week 16. These patients were classified as early responders and controls respectively. The 2 groups were compared by Mann-Whitney-U test. A generalized estimating equation (GEE) compared the 2 groups over the course of the 2-year trial per each of the 5 domains of the MFI, adjusting for baseline DAS28CRP and baseline MFI domain score.Results:Of the 379 patients recruited in the CareRA trial, 343 (90.5%) had a MFI score available at baseline and a DAS28CRP available at week 16 with 236 (68.8%) patients achieving remission, and 107 (31.2%) patients not achieving remission at week 16. After 2 years of treatment, the proportion of patients in DAS28CRP remission was still higher in the early responders versus controls (82.3% versus 63.5%, p=0.001). Every MFI domain after 2 years of treatment showed lower scores for early responders including general fatigue (p=0.017), physical fatigue (p=0.011), reduced activity (p=0.040) and mental fatigue (p=0.042) except reduced motivation (p=0.062) (see figure 1). GEE analysis demonstrated that all MFI domains differed over 2 years between patients in remission or not at week 16, including general fatigue (p&lt;0.001), physical fatigue (p&lt;0.001), reduced activity (p&lt;0.001), mental fatigue (p=0.037) and also reduced motivation (p=0.005).Figure 1.MFI domain scores at baseline and at week 104 per groupConclusion:Patients reaching remission after 16 weeks of treatment achieve lower fatigue levels over 2 years compared to patients not reaching this early remission. This study underlines the importance of early disease control. Successful early intensive treatment improves in the long run not only clinical outcomes but also an important patient preferred outcome such as fatigue.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

A novel, theory based intervention to promote engagement in physical activity in early rheumatoid arthritis

Purpose: People with Rheumatoid Arthritis (RA) have suggested they need support to engage with physical activity following their diagnosis. With patient input, and based upon previous research, we developed an intervention delivered by musculoskeletal physiotherapists in a primary care setting - Promoting Engagement in Physical Activity for Rheumatoid Arthritis (PEPA-RA). This consisted of four group and one individual session delivered over 12 weeks by a musculoskeletal physiotherapist in a primary care setting. Each session included patient education, support for behaviour change, and supervised practical exercise. The aim was to test the feasibility and acceptability of PEPA-RA to inform a future delivery and further research.

The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis.

In people with rheumatoid arthritis (RA), mental health problems are common, but often not recognized or treated, contributing to increased morbidity and mortality. Most studies examining the impact of mental health problems in RA have focused on depression. We aimed to determine the association between anxiety, and disease activity and quality of life (QoL) in people with RA. A systematic review and meta-analysis were performed. A protocol was registered with PROSPERO (CRD2-17062580). Databases (Web of Science, PsycINFO, CINAHL, Embase, Medline) were searched for studies examining the association between anxiety and disease activity and QoL, in adults with RA, from inception to February 2019. Primary outcome measures were DAS28 and SF-36. Eligibility screening and data extraction were completed by two reviewers. Disagreements were resolved by discussion or a third reviewer. Quality assessment was carried out using the Newcastle-Ottawa Scale. From 7712 unique citations, 60 articles were assessed for eligibility. The final review included 20 studies involving 7452 people with RA (14 cross-sectional, 6 cohort). Eleven examined disease activity, 6 reported QoL outcome measures and 3 included both. Anxiety was associated with increased disease activity and worse QoL. Meta-analysis showed anxiety to be correlated with increased DAS28 scores (r = 0.23, CI 0.14, 0.31) and reduced physical (r = - 0.39, CI - 0.57, - 0.20) and mental QoL (- 0.50, CI - 0.57, - 0.43). Anxiety in people with RA is associated with increased disease activity and worse QoL. Improved recognition and management of comorbid anxiety may help to improve outcomes for people with RA.Key Points• This is the first systematic review and meta-analysis to examine the relationship between anxiety and disease activity and QoL in people with RA.• Anxiety was associated with higher disease activity both cross-sectionally and at up to 12-month follow-up.• Anxiety may have a more significant impact on disease activity in early RA, highlighting the importance of early recognition and management of comorbid anxiety.• People with anxiety had poorer self-reported physical and mental QoL, although there was some heterogeneity in study findings, particularly for physical QoL (I2= 78.5%).

Diagnostic value of anti-fibrinogen citrullinated peptide in rheumatoid arthritis

ObjectiveTo determinate the diagnostic value of an antibody against a citrullinated fibrinogen peptide in Cuban patients with rheumatoid arthritis, using an enzyme immunoassay. Materials and methodsA citrullinated peptide of fibrinogen designed by informatics prediction was synthesised and used in an enzyme immunoassay. The participants were 81 patients with early disease, 81 patients with established disease, 58 patients with other rheumatic and inflammatory diseases, and 43 healthy individuals. Anti-citrullinated fibrinogen peptide, anti-mutated citrullinated vimentin, anti second generation citrullinated peptides and rheumatoid factor antibodies were determined by enzyme-linked immunosorbent assay. ResultsDetermination of anti-citrullinated peptide of fibrinogen antibodies by the designed enzyme immunoassay showed the best diagnostic value in early rheumatoid arthritis patients, with the highest value sensitivity (84%), negative predictive value (85%), Youden index (0.73%) and area under the receiver operating curve (0.9192). Specificity (89%) and positive predictive value (88%) were higher than rheumatoid factor, similar to anti-mutated citrullinated vimentin, but lower than second generation anti-citrullinated peptides assay. The positivity of C-reactive protein was associated with the presence of anti-citrullinated fibrinogen peptide antibodies and the titres of these antibodies correlated with clinical activity in early disease. ConclusionsThe immunoassay designed with a citrullinated fibrinogen peptide has a high diagnostic value and can identify patients with greater clinical activity in early rheumatoid arthritis.

E051 A novel, theory based intervention to promote engagement in physical activity in early rheumatoid arthritis: quantitative findings

E051 A novel, theory based intervention to promote engagement in physical activity in early rheumatoid arthritis: quantitative findings

042 “The pain doesn’t go, but it’s better since exercising”: promoting engagement in physical activity in early rheumatoid arthritis

042 “The pain doesn’t go, but it’s better since exercising”: promoting engagement in physical activity in early rheumatoid arthritis

Biologics: A tectonic shift in the management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints which if ongoing, has a significant bearing in the quality of life and has a variety of systemic manifestation which reduces the overall life span due to an ongoing inflammatory process. There has been a shift in the management of RA right from the early identification of the disease to targeting the pathogenic mechanisms. The changing modalities with emphasis on remission and low disease activity in early RA should be the primary goal. Disease control of RA with the use of combination synthetic disease modifying anti-rheumatic drugs or in combination with biological agents have improved disease-related outcomes. This prevents the progression of disease, morbidity, and has a significant bearing on the overall economic productivity of the patient and the society. Costs of the biological drugs is a major hurdle in their usage. Introduction of biosimilars have lead to a decrease in the cost of the biological molecules and hence their use becoming more widespread. The purpose of this review is to highlight the changing treatment modalities with the advent of biological disease modifiers in RA and a rationale for their use. The strategy in the treatment of RA should be goal directed rather than just relief of symptoms.

Costs and disease activity in early rheumatoid arthritis in 1996–2000 and 2006–2011, improved outcome and shift in distribution of costs: a two-year follow-up

Objective: To evaluate changes in healthcare utilization, costs, and disease activity from 1996 to 2011 for patients with early rheumatoid arthritis (RA).Method: Two cohorts of patients with early RA, included in 1996–1998 (T1) and 2006–2009 (T2), were followed regularly. Healthcare utilization, costs, and disease activity were compared between cohorts during 2 years after diagnosis.Results: Disease activity was significantly improved in T2 vs T1. Drug costs increased in T2 vs T1 (EUR 911 vs EUR 535, respectively; p = 0.017), and costs for RA-related hospitalization decreased. More than 90% in T2 were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion compared to 50% in T1. At 2 year follow-up, levels were still > 90% in T2, while corresponding values in T1 were just above 70%. Comparing T2 to T1, total direct costs were slightly higher in T2 (EUR 3941 vs EUR 3364, respectively; ns), sick leave decreased (EUR 3511 vs EUR 5672; p = 0.025), while disability pension increased slightly (EUR 4889 vs EUR 4244; ns), but total indirect costs remained unchanged (EUR 8400 vs EUR 9916; ns). Total direct and indirect costs did not differ between the cohorts (EUR 12 342 in T2 vs EUR 13 280 in T1; ns), and loss of productivity still represented the largest component of total costs.Conclusion: T2 patients were prescribed DMARDs earlier and more aggressively than T1 patients. Stable and better improvements in disease activity, function, and quality of life were achieved in T2 compared to T1. There was a shift within the components in direct costs and indirect costs, but total costs remained essentially unchanged.

Determinants of Perceived Health Nonimprovement in Early Rheumatoid Arthritis Patients With Favorable Treatment Outcomes.

To explore the association between achieving favorable clinical outcomes and patients' perceived change in overall health status after 12 months of treat-to-target in patients with early rheumatoid arthritis (RA) and to identify determinants of subjective nonimprovement. Baseline and 12-month data of patients included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study with at least a moderate response (by European League Against Rheumatism criteria) after 1 year were selected for analysis. Logistic regression analysis was used to identify factors associated with nonimproved perceived overall health status at 12 months. At 12 months, 75 of 210 patients (35%) did not consider their health to have improved despite having achieved favorable clinical outcomes. Relative change from baseline in pain (Wald = 20.20; P < 0.01) and fatigue (Wald = 5.58; P = 0.02) was independently associated with nonimproved perceived overall health status. The results were similar when only patients with ≤1 swollen joint were analyzed. An improvement of 55% in pain measured on a visual analog scale was found to discriminate reasonably well between patients who considered their health to have improved versus patients who did not, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.61-0.78). These results demonstrate that clinical improvements do not equate with improved subjective health for all patients. The association of nonimprovement with changes in pain and fatigue suggest that it might be worthwhile to monitor and address pain and fatigue in addition to and independently of disease activity in early RA.

Role of cartilage oligomeric matrix protein (COMP) as a prognostic biomarker in follow-up of early rheumatoid arthritis patients: Correlation to musculoskeletal ultrasonographic findings

Aim of the workTo assess the level of serum cartilage oligomeric matrix protein (COMP) in early rheumatoid arthritis (RA) patients and study its relation to disease activity and musculoskeletal ultrasound (MSUS) findings. Patients and methodsThe study included 40 early RA patients. Disease activity score (DAS28) was assessed. Serum COMP level was measured and MSUS findings of the small joints of hands done at base line and after 6 months of follow up.20 age and sex matched control were included. ResultsPatients age was 38.8 ± 9.3 years; 36 females and 4 males and disease duration 6.7 ± 3.5 years. Serum COMP was significantly higher in patients (median 190 U/L; 90–750 U/L) compared to control (90 U/L; 80–130 U/L)(p < .001) being higher in more active (250 U/L) (p = .001) and significantly correlated with baseline synovial inflammation (p = .009). COMP levels were lowered after 6 months of receiving treatment (110 U/L; 30–180 U/L) (p < .001). The presence of bony erosions increased with more active disease (p = .003). There was a significant reduction in the erythrocyte sedimentation rate and COMP at follow up (p < .0001 and p = .001 respectively). No correlation was found between the COMP level with C-reactive protein, ESR, MSUS score or bony erosions at follow up. ConclusionsCOMP significantly correlated with disease activity in early RA and could be used as a marker of activity. It correlates significantly with synovial inflammation detected by power Doppler. COMP may reflect the outcome and could be used as a prognostic marker in RA patients. COMP did not significantly correlate with bone erosions.

High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis.

Adverse events (AEs) are common during disease-modifying antirheumatic drug (DMARD) treatment, but their influence on treatment results is unclear. We studied AEs in relation to disease activity in early rheumatoid arthritis (RA). Ninety-nine patients started intensive treatment with three conventional synthetic DMARDs (csDMARDs) and oral prednisolone, and were randomized to a 6-month induction treatment with infliximab or placebo. All AEs during the first 12months of treatment were recorded. We scored each AE based on severity (scale 1-4) and defined the burden of AEs as the sum of these scores. Patients were divided into tertiles according to the burden of AEs. As outcomes, we assessed 28-joint disease activity score (DAS28) levels and remission rates at 12 and 24months. Three hundred thirty-one AEs in 99 patients were reported, and 27 (8%) were categorized as severe or serious. Mean burden of AEs per patient was 5.4 ± 4.3. Seventy-nine AEs (24%) led to temporary (n = 52) or permanent (n = 27) csDMARD discontinuation. Of discontinuations, 1, 21, and 57 were detected in the first, second, and third tertiles, respectively. DAS28 remission rates decreased across tertiles at 12months (94, 94, and 76%; p for linearity 0.029) and at 24months (90, 86, and 70%; p for linearity 0.021). Mean DAS28 levels increased across tertiles at 12months (1.5 ± 1.0, 1.7 ± 0.9, and 1.9 ± 1.2; p for linearity 0.021) and at 24months (1.4 ± 0.8, 1.6 ± 1.0, and 1.9 ± 1.1; p for linearity 0.007). High burden of AEs is associated with higher disease activity and lower likelihood of remission in early RA.

Conséquences du tabac sur le devenir de la polyarthrite rhumatoïde

Tobacco, that is a well-known risk factor for rheumatoid arthritis (RA) development, can have an impact on disease outcome. Data are rather well-documented about active smoking. Concerning disease activity, there are contradictory results. While smoking is associated to a more important articular and systemic activity in early RA, it is not predictive of a persistent disease activity. In terms of disease severity, current smoking is not related to a higher radiographic progression and would have “protective effects”. But it enhances the occurrence of extra-articular manifestations (nodules, interstitial lung disease, periodontitis, vasculitis) and increases the risk of severe infections, periprosthetic joint infection, lung cancer and mortality. Whatever the immunological status, smoking is linked to a lower response to methotrexate and to the 3 TNF-blocking agents (infliximab, etanercept and adalimumab) that have been assessed until now. No informations are available about the other biologic agents. Moreover, remission and drug survival rates are lower under tobacco exposure. Nevertheless, active smoking has no deleterious effect in case of dose reduction or drug discontinuation. Although smoking cessation, which is an objective difficult to achieve because of several well-identified brakes, does not modify disease activity, its interest remains to reduce the appearance of extra-articular manifestations, severe infections and the risk of premature mortality due to cardiorespiratory comorbidities or cancer.