M. Hazes

Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial

Objective To determine the most effective induction disease-modifying antirheumatic drug (DMARD) strategy in early rheumatoid arthritis (RA), second to compare one single dose of intramuscular glucocorticoids (GCs) with daily oral GCs during the induction phase. Methods The 3-month data of a single-blinded clinical trial in patients with recent-onset arthritis (tREACH) were used. Patients were included who had a high probability (>70%) of progressing to persistent arthritis, based on the prediction model of Visser. Patients were randomised into three induction therapy strategies: (A) combination therapy (methotrexate (MTX) + sulfasalazine + hydroxychloroquine) with GCs intramuscularly; (B) combination therapy with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. A total of 281 patients were randomly assigned to strategy (A) (n=91), (B) (n=93) or (C) (n=97). Results The Disease Activity Score (DAS) after 3 months was lower in patients receiving initial combination therapy than in those receiving MTX monotherapy (0.39 (0.67 to 0.11, 95% CI)). DAS did not differ between the different GC bridging treatments. After 3 months 50% fewer biological agents were prescribed in the combination therapy groups. Although the proportion of patients with medication adjustments differed significantly between the treatment arms, no differences were seen in these adjustments due to adverse events after stratification for drug. Conclusion Triple DMARD induction therapy is better than MTX monotherapy in early RA. Furthermore, no differences were seen in medication adjustments due to adverse events after stratification for drug. Intramuscular and oral GCs are equally effective as bridging treatments and both can be used.

Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study

BackgroundVarious cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA.MethodsPolymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed.ResultsThe IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity.ConclusionsWe here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

Disease activity or remission of rheumatoid arthritis before, during and following pregnancy

Purpose of reviewDisease activity of rheumatoid arthritis (RA) can ameliorate spontaneously during pregnancy; however, adequate measurement of disease activity during pregnancy is a challenge, as is quantifying disease improvement during pregnancy and disease flare postpartum. Adverse pregnancy outcomes may be related to high disease activity during pregnancy, the full extent of which remains to be fully defined. Recent findingsDisease activity might best be measured during pregnancy with DAS28-CRP without visual analogue scale (VAS) general health. Pregnancy outcome seems to be worse in patients with RA compared with healthy controls. High disease activity of RA may contribute importantly both to the longer time to conceive and worse pregnancy outcome. SummaryLow disease activity of RA before, during and after pregnancy may be best for both mother and child. Counselling of patients on reproductive health and preconception treat-to-target management may help to achieve lower disease activity. This may result in better pregnancy outcomes.

Marked underdiagnosis and undertreatment of hypertension and hypercholesterolaemia in rheumatoid arthritis

OBJECTIVE To investigate the prevalence of underdiagnosis and undertreatment of traditional cardiovascular risk factors in RA patients. METHODS RA patients ⩽70 years of age without cardiovascular disease (CVD) or diabetes mellitus were included. Systolic blood pressure and a fasting lipid profile were measured. The 10-year CVD risk was estimated using the Dutch Cardiovascular Risk Management (CVRM) guideline and EULAR modifications of the Systemic Coronary Risk Evaluation tables. RESULTS A total of 327 patients were included (female gender: 68%). The mean age was 53 (11) years [mean (s.d.)]. The median disease duration was 7 years (inter quartile range: 2-14 years). According to the CVRM guideline, 52% of the patients had a CVD risk ⩾20% and according to the EULAR guidelines, 18% of the patients had a CVD risk ≥ 20%. Low-density lipoprotein cholesterol (LDL-C) >2.5 mmol/l was found in >80% of the patients with a CVD risk ⩾10% as estimated by both the CVRM and EULAR guidelines, and 32-42% of the patients with a CVD risk ⩾10% had a systolic blood pressure >140 mmHg, depending on the risk model used. Statins were used in 6% and antihypertensives in 23-25%, and 50-86% of these patients did not reach the recommended treatment targets. CONCLUSION Regardless of the adapted risk assessment model used, untreated hypertension and hypercholesterolaemia were frequently found in RA patients with increased CVD risk. Treatment of these cardiovascular risk factors deserves more attention in RA. TRIAL REGISTRATION The Dutch Trial Register, www.trialregister.nl, NTR3873.

Circulating maternal cytokines influence fetal growth in pregnant women with rheumatoid arthritis

Background High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. Objectives To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy. Methods This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied. Results During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs. Conclusions Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.

Association of Cardiovascular Risk Factors with Carotid Intima Media Thickness in Patients with Rheumatoid Arthritis with Low Disease Activity Compared to Controls: A Cross-Sectional Study

Objectives Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. Methods Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. Results In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR 2–14 years). The median DAS28 was 2.4 (IQR 1.6–3.2) and 114 (50.4%) of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis). Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001) and systolic blood pressure (B = 0.003, P = 0.003). In controls, cIMT was associated with age (B = 0.006, P<0.001) and smoking (B = 0.097, P = 0.001). Conclusion cIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort.

Adherence to cardiovascular prevention strategies in patients with rheumatoid arthritis

Objectives: Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular disease (CVD). Recent national and international guidelines suggest strict treatment of CVD risk factors in RA. The aim of this study was to evaluate the self-reported adherence to CV prevention strategies in patients with RA. Method: RA patients visiting an outpatient clinic for strict CVD risk management received a validated questionnaire to evaluate adherence to CV prevention strategies. Strict treatment targets were defined and lifestyle recommendations were given following a prespecified protocol. CVD risk was assessed using the SCORE algorithm. Results: In total, 111 questionnaires were returned (response rate of 82%). A high 10-year CVD risk (≥ 20%) was present in 53%, but only 3% thought they had an increased CVD risk. A total of 53% of patients reported that they ‘follow the doctors’ suggestions exactly’ and 75% reported finding it ‘easy to follow the suggestions’. Of the 69% of patients who were prescribed lipid- and/or blood pressure-lowering drugs, 90% reported taking all prescribed tablets. The advice to follow a diet was given to 42%, of whom 68% said they followed the advised diet. Physical exercise was advised to 67%, of whom 62% said they performed specific physical exercise on at least 3 days a week. The adherence to lifestyle recommendations was not significantly different across the CVD risk groups. Conclusions: RA patients tend to underestimate their CVD risk. The self-reported adherence of RA patients to CVD risk management was high concerning pharmaceutical interventions and moderate in the case of lifestyle interventions.

THU0108 No Clear Association Between the Presence of Subclinical Synovitis and Patient Reported Outcomes in RA Patients in Remission

Background Several studies assessed disease activity with ultrasound in rheumatoid arthritis (RA) patients who were in clinical remission. These studies found subclinical synovitis in 48-73% of the patients. Subclinical synovitis is associated with radiographic progression and predicts short-term relapse in RA patients. So far, little is known about the association between subclinical synovitis and patient reported outcomes (PROs). Objectives We evaluated the frequency of subclinical synovitis detected by ultrasound in RA patients in clinical remission while they are continuing synthetic and biological DMARDs. Our second objective was to compare PROs between patients with and without subclinical synovitis. Methods Patients who are treated with the combination of a synthetic DMARD and biological DMARD (adalimumab or etanercept) and have low disease activity (DAS44<2.4 and SJC ≤1) were examined by ultrasound at baseline and after three months follow-up. Ultrasound examination included 26 joints (MCP2-5, PIP2-5, wrists, MTP2-5) graded on greyscale (GS; 0-3) and power Doppler (PD; 0-3). A joint with subclinical synovitis was defined as GS>1 and/or PD>0. Data on clinical and psychological characteristics, demographics, pain scores, functional ability (HAQ) and health-related quality of life (SF-36) were collected at baseline and at three months. Coping (Pain Coping and Cognition List [PCCL]), depression/anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Bristol RA Fatigue Multi-Dimensional Questionnaire [BRAF-MDQ] and Fatigue Assessment Scale [FAS]) were collected at three months follow-up. Ultrasound subclinical synovitis positive and negative patients were compared on their PROs using the Wilcoxon-Mann-Whitney test and Chi-square test. Results At baseline, 89 patients were included of which 71 patients had had their three months evaluation. Ultrasound revealed subclinical synovitis in 64% of the patients at baseline and in 68% at three months. In 44% of the patients subclinical synovitis was detected at both measurements. figure 1 shows baseline characteristics and patient reported outcomes at baseline and after three months. No clear pattern emerged on the PROs scores between subclinical synovitis positive and negative patients. At baseline functional ability differed between the two groups while health-related quality of life was similar. At three months similar levels were observed for functional ability, health-related quality of life, coping, depression symptoms and fatigue. HADS anxiety differed at 3 months. Conclusions Subclinical synovitis is common in RA patients in clinical remission while they continue synthetic and biological DMARDs. In our study population we could not find a clear association between subclinical synovitis and PROs. Disclosure of Interest None declared

FRI0562 Ultrasound Enthesitis in Primary Care Psoriasis Patients with Musculoskeletal Complaints

Background Psoriasis patients with enthesitis can classify as psoriatic arthritis since the introduction of the CASPAR classification criteria in 2006. However, clinical assessment of the entheses could be challenging. In addition, the presence of a tender enthesis is not necessarily indicative for underlying inflammatory disease as it could be related to overuse, metabolic disease or ageing. Therefore, we need a better way to identify the inflammatory component of entheseal involvement in psoriasis. To detect these inflammatory components in the entheses, ultrasound (US) examination can be used to identify inflammatory disease at the entheses. Objectives Our aims were to determine the prevalence of US abnormalities among psoriasis patients in primary care and to determine the concordance of clinical and US information at individual entheseal sites. Methods Adult patients with psoriasis were invited to participate in the SENSOR study. Patients who reported pain in joints, entheses or the lower back were eligible for clinical evaluation. If physical examination indicated a painful enthesis on the LEI/MASES or if arthritis was present, US examination of the entheses was performed. The six entheses of the Madrid Sonographic Enthesis Index (MASEI) and the lateral epicondyle tendon insertion (elbow) were evaluated according to the MASEI scoring system. Enthesitis was defined as US inflammation (positive power Doppler (PD) signal or a thickened enthesis of the plantar fascia) in combination with one clinical feature at the same enthesis. Structural changes detected by ultrasound were calcifications, increased thickness, irregular fibre structure and erosions. Results Of 524 patients who participated in the SENSOR study, 111 patients were assessed both by physical examination and by US. In 106 (95%) patients we detected US abnormalities. In 56 (50%) patients we found structural changes without indication for inflammatory disease. In 50 (45%) patients we found US abnormalities indicating inflammatory disease at the enthesis (positive PD: n=35; thickened plantar fascia: n=15). When we combined the US data with the clinical information, 36% of US inflammatory disease were confirmed [Figure 1]. Conclusions We found US abnormalities in 95% of the primary care psoriasis patients with musculoskeletal complaints, which is a combination of both structural and inflammatory US components. In 45% of primary care psoriasis patients we observed US inflammatory disease, which was confirmed in 36% of the patients by clinical information. Acknowledgements This study was financially funded by an investigator-initiated grant from Pfizer bv. Disclosure of Interest None declared

SAT0103 Three-monthly ultrasound monitoring of rheumatoid arthritis patients tapering their medication has limited value in predicting disease relapse

Background Prognostic factors that may guide tapering decisions for DMARDs and TNFi on individual patient level are not available. To improve successful tapering subclinical synovitis may play a role in maintaining the remission state. Studies using ultrasound suggest that the presence of subclinical synovitis may elicit early disease relapse in remission. Objectives Our aim is to determine if ultrasound synovitis precedes disease relapse while tapering synthetic DMARD (sDMARD) or TNFi in patients with RA who achieved clinical remission on sDMARD and TNFi. Methods We included 125 RA patients (aged>17 years) treated with an sDMARD and a TNF-inhibitor who were in remission (DAS44≤2.4 & SJC≤1). Demographic characteristics, swollen and tender joints, laboratory variables and ultrasound synovitis (MCP2-5; PIP2-5; wrists; MTP2-5) were recorded at each visit (every three months) during one year follow-up. Patients were randomised to two tapering strategies: i) tapering sDMARD; ii) tapering TNFi. Disease relapse was defined as DAS44>2.4 or SJC>1. Ultrasound synovitis was defined as GS≤1 and/or PD≤0. To estimate whether ultrasound is able to identify patients who will have a disease relapse within three months follow-up a Cox proportional regression model for time to event data was used. Results: Ultrasound synovitis was found in 58% of RA patients in clinical remission. After one year follow-up 36% of RA patients had a disease relapse of whom 60% had ultrasound synovitis at baseline. table 1 shows the distribution of relapse en ultrasound synovitis for every three months. In the multivariate Cox model increasing number of joints with ultrasound synovitis was not significantly associated with disease relapse within three months follow-up (HR 1.21; 95%CI: 0.97-1.51) [table 2].Table 1 Distribution of disease relapse and US synovitis during follow-up, n (%) T0 T3 T6 T9 T12 US synovitis 72/125 (58) 60/124 (48) 62/112 (55) 40/96 (42) - Disease relapse 0 6/124 (5) 8/112 (7) 23/96 (24) 8/67 (12) US synovitis at previous visit - 4/6 (67) 5/8 (63) 14/23 (61) 6/8 (75) No disease relapse 0 118/124 (95) 104/112 (93) 73/93 (78) 59/67 (88) No US synovitis at previous visit - 46/118 (39) 47/104 (45) 23/73 (32) 29/59 (49) US = ultrasound Table 2 Multivariate Cox model with US synovitis or PD synovitis for disease relapse Model US synovitis HR (95% CI) Model PD synovitis HR (95% CI) Age 0.99 (0.97-1.02) 0.99 (0.97-1.02) Gender 1.08 (0.53-2.17) 1.05 (0.53-2.11) Time since diagnosis 1.02 (0.92-1.13) 1.03 (0.93-1.14) ACCP 0.47 (0.24-0.91) 0.51 (0.27-0.97) DAS (at time of US) 2.25 (1.21-4.19) 2.34 (1.25-4.41) US synovitis 1.21 (0.97-1.51) PD synovitis 1.35 (1.02-1.80) US = ultrasound; PD = power Doppler; HR = hazard ratio; ACCP=anti-cyclic citrullinated peptide antibody; DAS = disease activity score Conclusions Monitoring RA patients who started tapering their medication every three months showed limited value for ultrasound to identify patients who will have a disease relapse. Disclosure of Interest: None declared