Glucose management team significantly improves glycaemic care and commitment to in-hospital guidelines within arthroplastic patients.

BACKGROUND: Perioperative dysglycaemias are a risk for harm but guidelines to improve glucose management are poorly adhered to. AIM: To determine whether a specialized team and diabetes education improves the implementation of guidelines and glucose values. METHODS: We conducted a prospective study of 611 nonselected, consecutive patients attending for elective hip or knee arthroplasty. The first 209 patients received conventional care and the following 402 patients received intervention (Acute Glucose Service, AGS) in two chronological groups; either perioperatively (AGS1) or also preoperatively (AGS2). The AGS-team provided diabetes education, identified the patients with diabetes risk and adjusted the medication when needed. Capillary plasma glucose (CPG) was repeatedly measured and glycated haemoglobin (HbA1c) obtained before and after the surgery. The study objectives were to evaluate the staff actions when hyperglycaemia was severe (CPG >10 mmol/L), and to assess improvement of the glycaemic values and the complication rate within 3 months. RESULTS: None of the severely hyperglycaemic events in the reference group were treated according to guidelines. In the AGS 1 group, 50% and in the AGS2 group, 53% were appropriately managed (p < .001). The events of hyperglycaemia (CPG >7.8 mmol/L at least twice) and of severe hyperglycaemia (CPG >10 mmol/L) decreased in all patient groups. The medians of the highest, mean and variability of CPG values improved. The mean HbA1c improved significantly within AGS 2. There was no association between improved glycaemic care and early complications. CONCLUSIONS: AGS intervention significantly improves adherence to guidelines and glucose values.

Adalimumab and sulfasalazine in alleviating sacroiliac and aortic inflammation detected in PET/CT in patients with axial spondyloarthritis: PETSPA.

AIM: Inflammatory signals in the sacroiliac (SI) joints and the aorta of patients with axial spondyloarthritis (axSpA) were graded by positron emission tomography/computed tomography (PET/CT) imaging before and after treatment with sulfasalazine (SSZ) or adalimumab (ADA). METHODS: Patients with axSpA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, were recruited. Disease-modifying antirheumatic drug-naïve patients started SSZ for 12 weeks, whereas those with prestudy treatment with or contraindication to SSZ commenced ADA for 16 weeks. In addition, those patients in the SSZ group with insufficient response commenced ADA for 16 weeks. 18F-fluorodeoxyglucose PET/CT was performed after inclusion and after treatment with SSZ and ADA. Maximum standardized uptake value (SUVmax) was assessed for the aorta and the SI joints, and maximal target-to-blood-pool ratio (TBRmax) only for the aorta. RESULTS: Among five SSZ patients, mean ± SD BASDAI was 4.7 ± 1.6 before and 3.5 ± 1.4 after treatment (p = .101). In 13 ADA patients, the BASDAI decreased from 5.4 ± 1.6 to 2.8 ± 2.2 (p < .001). Among the SSZ patients, SUVmax in SI joints decreased from 2.35 ± 0.55 to 1.51 ± 0.22 (-35.8%, p = .029). Aortic TBRmax decreased from 1.59 ± 0.43 to 1.26 ± 0.26 (-33.2%, p = .087). In the ADA patients, SUVmax in the SI joints was 1.92 ± 0.65 before and 1.88 ± 0.54 after treatment (-1.8%, p = .808) and TBRmax in the aorta 1.50 ± 0.60 before and 1.40 ± 0.26 after treatment (-6.7%, p = .485). CONCLUSIONS: Our small open-label study showed that SSZ may reduce PET-CT-detectable inflammation in the SI joints, with a trend towards a reduction in the aorta.

Pain experience in an aging adult population during a 10-year follow-up.

OBJECTIVES: This 10-year follow-up study aimed to examine the persistence of SF-36 pain intensity and pain-related interference and to identify baseline factors that may relate to pain experience among community-dwelling aging adults. METHODS: Questionnaire and clinical data on a total of 1,954 participants (mean age at baseline 63 years) were collected in 2002, 2005, 2008, and 2012. Based on pain reports, four pain intensity, pain interference (PIPI) groups were formed at each time point: PIPI group I: none to mild pain intensity and interference; II: moderate to extreme pain intensity, none to mild pain-related interference; III: None to mild pain intensity, moderate to extreme pain-related interference, IV: Moderate to extreme pain intensity and interference. RESULTS: Participants with the most pain at baseline improved their pain situation the most during the follow-up. Higher BMI was associated with pain interference, and metabolic syndrome (MetS) and musculoskeletal diseases with both pain intensity and interference (p<0.05, statistically significant interaction between pain intensity and pain interference) at baseline. According to multivariate logistic regression analysis the following baseline characteristics were associated with remaining in PIPI group I throughout the follow-up: presence of musculoskeletal disease (OR 0.22 [95% CI 0.16-0.30]), high BMI (OR 0.93 [95% CI 0.90-0.97]), high household income (OR 1.46 [95% CI 1.07-1.98]), good childhood home environment (OR 1.03 [95% CI 1.00-1.05]). CONCLUSIONS: Multiple factors may affect pain persistence in late adulthood with varying effect on pain intensity and pain-related interference. Pain situation of even those with most pain may be improved.

Analgesic purchases among older adults - a population-based study.

BACKGROUND: Pain is a frequent and inevitable factor affecting the quality of life among older people. Several studies have highlighted the ineffectiveness of treating chronic pain among the aged population, and little is known about the prevalence of analgesics administration among community-dwelling older adults. The objective was to examine older adults' prescription analgesic purchases in relation to SF-36 pain in a population-based setting. METHODS: One thousand four hundred twenty community-dwelling citizens aged 62-86 years self-reported SF-36 bodily pain (pain intensity and pain-related interference) scores for the previous 4 weeks. The Social Insurance Institution of Finland register data on analgesic purchases for 6 months prior to and 6 months after the questionnaire data collection were considered. Special interest was focused on factors related to opioid purchases. RESULTS: Of all participants, 84% had purchased prescription analgesics during 1 year. NSAIDs were most frequently purchased (77%), while 41% had purchased paracetamol, 32% opioids, 17% gabapentinoids, and 7% tricyclic antidepressants. Age made no marked difference in purchasing prevalence. The number of morbidities was independently associated with analgesic purchases in all subjects and metabolic syndrome also with opioid purchases in subjects who had not reported any pain. DISCUSSION: Substantial NSAID and opioid purchases emerged. The importance of proper pain assessment and individual deliberation in terms of analgesic contraindications and pain quality, as well as non-pharmacological pain management, need to be highlighted in order to optimize older adults' pain management.

Perioperative hyperglycaemia in elective arthroplasties. Should we do better?

BACKGROUND: Perioperative dysglycaemia is associated with deleterious outcomes but guidelines to improve glucose management are poorly or inconsistently adhered to. We evaluated glucose management among diabetic and non-diabetic patients undergoing elective hip or knee arthroplasty. METHODS: Capillary plasma glucose (CPG) was measured prospectively four times daily of 209 patients undergoing elective hip or knee surgery. Actions of the attending teams to CPG values and detection of patients at risk were analysed. RESULTS: A total of 209 patients were enrolled. All diabetic patients on insulin (6/6) had hyperglycaemia (≥7.8 mmol/l) more than twice and severe hyperglycaemia (>10 mmol/l) at least once. Of the 27 diabetic patients not on insulin 26 (96.3%) had CPG ≥ 7.8 mmol/l ≥ 2 times and 17 (63%) >10 mmol/l. The corresponding figures of the 176 non-diabetic patients were 137 (77.8%) and 61 (34.7%). Severe hyperglycaemia occurred in 54/176 (30.1%) of the non-diabetic patients with pre-operative HbA1c < 42 mmol/mol and random plasma glucose < 7.8 mmol/l. Of the 84 hyperglycaemic episodes > 10 mmol/l, none was treated. Patients with a FINDRISC score ≥ 12 (corresponding to moderate to high risk of diabetes) and hyperglycaemia went unnoticed. CONCLUSIONS: Hyperglycaemia is common among elective orthopaedic surgery patients with or without diabetes. More than 80% of the 209 patients had hyperglycaemia and 40% had severe hyperglycaemia. None of the patients was treated according to guidelines and none of the patients at risk of hyperglycaemia or diabetes was noticed. There is an obvious need for further education and support by diabetes specialists. CLINICAL TRIAL REGISTRATION: Clinical trials, gov. NCT03306810.

Automated Text Message-Enhanced Monitoring Versus Routine Monitoring in Early Rheumatoid Arthritis: A Randomized Trial.

OBJECTIVE: Frequent monitoring of patients with early rheumatoid arthritis (RA) is required for achieving good outcomes. This study was undertaken to investigate the influence of text message (SMS)-enhanced monitoring on early RA outcomes. METHODS: We randomized 166 patients with early, disease-modifying antirheumatic drug-naive RA to receive SMS-enhanced follow-up or routine care. All patients attended visits at 0, 3, and 6 months, and a follow-up visit at 12 months. Treatment was at the physicians' discretion. The intervention included 13 SMSs during weeks 0-24 with questions concerning medication problems (yes/no) and disease activity (patient global assessment [PtGA], scale 0-10). Patients were contacted if response SMSs indicated medication problems or PtGA exceeded predefined thresholds. Primary outcome was 6-month Boolean remission (no swollen or tender joints and normal C-reactive protein levels). Quality of life (QoL; measured by the Short Form 36 survey) and Disease Activity Score in 28 joints (DAS28) were assessed. RESULTS: Six and 12-month follow-up data were available for 162 and 157 patients, respectively. In the intervention group, 46% of the patients (38 of 82) reported medication problems and 49% (40 of 82) reported text message PtGAs above the alarm limit. Remission rates at 6 months (P = 0.34) were 51% in the intervention group and 42% in the control group. These rates were 57% and 43% at 12 months (P = 0.17) in the intervention and control groups, respectively. The respective mean ± SD DAS28 scores for the intervention and control groups were 1.92 ± 1.12 and 2.22 ± 1.11 at 6 months (P = 0.09); and 1.79 ± 0.91 and 2.08 ± 1.22 at 12 months (P = 0.28). No differences in QoL were observed. CONCLUSION: The study did not meet the primary outcome despite a trend favoring the intervention group. This may be explained by the notably high overall remission rates.

Decreasing trend in the incidence of serious pneumonias in Finnish children with juvenile idiopathic arthritis.

OBJECTIVES: Children with juvenile idiopathic arthritis (JIA) may be predisposed to serious pneumonia due to modern disease-modifying anti-rheumatic treatment. In this nationwide retrospective study with clinical data, we describe the pneumonia episodes among children with JIA. METHODS: Patients under 18 years of age with JIA and pneumonia during 1998-2014 were identified in the National Hospital Discharge Register in Finland. Each individual patient record was reviewed, and detailed data on patients with JIA and pneumonia were retrieved, recorded, and analyzed. If the patient was hospitalized or received intravenous antibiotics, the pneumonia was considered serious. RESULTS: There were 157 episodes of pneumonia among 140 children with JIA; 111 episodes (71%) were serious (80% in 1998-2006 and 66% in 2007-2014). The mean age of the patients was 9 years. Forty-eight percent had active JIA and 46% had comorbidities. Disease-modifying anti-rheumatic drugs (DMARD) were used at the time of 135 episodes (86%): methotrexate (MTX) by 62% and biologic DMARDs (bDMARD) by 30%. There was no significant difference in the use of bDMARDs, MTX and glucocorticoids between the patient groups with serious and non-serious pneumonia episodes. During six of the episodes, intensive care was needed. Two patients (1.3%) died, the remaining ones recovered fully. CONCLUSIONS: Although the incidence of pneumonia and the use of immunosuppressive treatment among children with JIA increased from 1998 to 2014, the proportion of serious pneumonias in these patients decreased. There was no significant difference in the use of anti-rheumatic medication between patients with serious and non-serious pneumonia.Key Points• The incidence of serious pneumonias decreased from 1998 to 2014 among children with juvenile idiopathic arthritis (JIA).• There was no significant difference in the use of the disease-modifying anti-rheumatic medication between JIA patients with serious and non-serious pneumonias.• Active JIA, comorbidities, and combination medication were associated with nearly half of the pneumonias.

Tuberculosis in people with rheumatic disease in Finland 1995-2007: a nationwide retrospective register study.

OBJECTIVES: RA and its medication, especially TNF-α inhibitors, increase the risk of clinical tuberculosis (TB) infection. We aimed to investigate the clinical manifestations, incidence and temporal changes in TB occurring concurrently with rheumatic diseases (RDs) between 1995 and 2007. METHODS: We combined the register of the Social Insurance Institution of Finland and the National Infectious Disease Register to find adult patients with reimbursed DMARDs and with a TB notification between 1995 and 2007. After reviewing the medical records, we described their clinical manifestations and medications, explored TB incidence trends using Poisson regression, and compared the incidence of TB with that of the general population. RESULTS: We identified 291 patients with both TB and rheumatic disease (RD), 196 of whom had RA. Between 1995 and 2007, the incidence of TB in adult RD decreased from 58.8 to 30.0 per 100 000 (trend P < 0.001, average marginal effect -3.4/100 000 per year, 95% CI -4.4, -2.4). Compared with the general population, the incidence was ∼4-fold. Among RD patients, pulmonary TB was the most common form of TB (72.6%). Disseminated TB was present in 56 (19.6%) patients. CONCLUSION: The incidence of TB among RD patients was ∼4-fold that of the general population, and it declined between 1995 and 2007. Disseminated TB was present in nearly 20% of patients.

Pain-related factors in older adults.

BACKGROUND AND AIMS: Pain is an evident factor affecting the quality of life in all age groups. The objective was to examine the prevalence of self-reported SF-36 bodily pain and pain-related factors in community-dwelling older adults. METHODS: One thousand four hundred and twenty adults aged 62-86 years self-reported SF-36 bodily pain during the previous month. For the analysis, four pain groups were formed (group I [0-45, moderate to very severe pain intensity and interference], group II [47.5-70], group III [77.5-90], and group IV [100, no pain at all]). Additional questionnaire-provided data regarding education, wealth, life habits, and morbidity, as well as clinical data were considered. RESULTS: The overall pain prevalence was 78% (SF-36 bodily pain score <100). The prevalence of cohabiting, as well as the years of education and household income were found to decrease with an increasing SF-36 bodily pain score. The prevalence of a BMI of over 30 and of central obesity emerged as the highest in group I. Morbidities were found to be most prevalent in group I. CONCLUSIONS: A high prevalence of intense and interfering pain was reported. Multiple factors that were found to relate to pain have previously been demonstrated to associate with social exclusion. Increasing attention should be paid to distinguishing these factors in patients with pain, as well as targeted pain assessment and measures to improve the sense of community among older adults. IMPLICATIONS: There is a lack of large studies that examine a wide scale of pain-related factors in the older adult population. To distinguish subjects with multiple such factors would help medical professionals to target their attention to patients at a high risk of chronic pain.

Long-term prognostic impact of hyperuricemia in community.

The debate whether an elevated level of serum uric acid (SUA) is an independent marker of cardiovascular risk is still going on. We examined morbidity and mortality related to SUA and hyperuricemia in a well-characterized population with very long follow-up. Study included 4696 participants (aged 30-59 years at baseline) of the coronary heart disease (CHD) Study of the Finnish Mobile Clinic Health Examination Survey. Adjusted hazard ratios (HRs) of hyperuricemia (defined as ≥360 µmol/l and ≥420 µmol/l) and SUA quintiles for mortality and adverse cardiovascular outcomes are reported. During the mean follow up of 30.6 years there were 2723 deaths, 887 deaths for CHD of which 340 were classified as sudden cardiac deaths, 1642 hospitalizations due to CHD and 798 hospitalizations due to congestive heart failure. After adjusting to baseline risk factors and presence of cardiovascular diseases as well as the use of diuretics there were no significant differences in the risk of any of the outcomes when analyzed either according to quintiles of SUA or using a cut-off point SUA ≥360 µmol/l for hyperuricemia. Only a rare finding of hyperuricemia SUA ≥420 µmol/l among women (n = 17, 0.9%) was independently associated with significantly higher risk of mortality (adjusted HR: 2.59, 95% CI: 1.54-4.34) and a combination end-point of major adverse cardiac events (MACEs) (HR: 2.69; 95% CI: 1.56-4.66). SUA was not an independent indicator of morbidity and mortality, with the exception of particularly high levels of SUA among women.

Early Targeted Combination Treatment With Conventional Synthetic Disease-Modifying Antirheumatic Drugs and Long-Term Outcomes in Rheumatoid Arthritis: Ten-Year Follow-Up Results of a Randomized Clinical Trial.

OBJECTIVE: The short-term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well-established, but the long-term success of such strategies is speculative, as is the role of early add-on biologics. We assessed the 10-year outcomes of patients with early RA treated with initial remission-targeted triple combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), 7.5-mg prednisolone, and additional infliximab (IFX) or placebo infusions. METHODS: Ninety-nine patients with early, DMARD-naive RA were treated with a triple combination of csDMARDs and prednisolone and randomized to double-blind receipt of infusions of either IFX (the Finnish Rheumatoid Arthritis Combination Therapy Trial [FIN-RACo] + IFX) or placebo (FIN-RACo + placebo) during the first 6 months. After 2 years, the treatment strategies became unrestricted, but the treatment goal was strict remission in the TNF-Blocking Therapy in Combination With Disease-Modifying Antirheumatic Drugs in Early Rheumatoid Arthritis (NEO-RACo) study. At 10 years, the clinical and radiographic outcomes and the drug treatments used between 5 and 10 years were assessed. RESULTS: Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo + IFX and 47 in the FIN-RACo + placebo group. At 10 years, the respective proportions of patients in strict NEO-RACo remission and in Disease Activity Score using 28 joints remission in the FIN-RACo + IFX and FIN-RACo + placebo groups were 46% and 38% (P = 0.46) and 82% and 72% (P = 0.29), respectively. The mean total Sharp/van der Heijde score was 9.8 in the FIN-RACo + IFX and 7.3 in the FIN-RACo + placebo group (P = 0.34). During the 10-year follow-up, 26% of the FIN-RACo + IFX group and 30% of the FIN-RACo + placebo group had received biologics (P = 0.74). CONCLUSION: In early RA, excellent results can be maintained up until 10 years in most patients treated with initial combination csDMARDs and remission-targeted strategy, regardless of initial IFX/placebo infusions.

Pneumonia in children with juvenile idiopathic arthritis in Finland 1999-2014: a nationwide retrospective register linkage study.

OBJECTIVES: To compare the incidence of pneumonia in children with juvenile idiopathic arthritis (JIA) to the aged-matched general population and to evaluate the use of anti-rheumatic medication among children with JIA and pneumonia. METHODS: The National Hospital Discharge Register collects data on ICD-diagnoses of hospital patients in Finland. From this register, patients with JIA under 18 years of age with pneumonia from 1999 through 2014 were identified. The control group consisted of age-matched patients derived from the general population with a diagnosis of pneumonia made in the same calendar year as the pneumonia of the JIA patients. The patient records of the children with JIA were scrutinised for the use of anti-rheumatic medication. RESULTS: We identified 223 pneumonias among the JIA patients (56,161 patient-years) and 53,058 pneumonias in the control group (17,546,609 person-years). The incidence of pneumonia in children with JIA was 386 (annual range 131-639) and in the control group 303 (annual range 225-438) per 100,000 person-years. The incidence of pneumonia increased significantly over time among JIA patients (p=0.013) and in the control group (p<0.001). Through 2007-2014 the rate of pneumonia was significantly higher among children with JIA (p<0.001) than control children. We found 150 JIA patients with pneumonia confirmed by positive chest radiograph. Altogether 47% of the JIA patients had combination medication. The use of methotrexate and biologic agents increased significantly over time (p=0.016 and p<0.001, respectively). CONCLUSIONS: The incidence of pneumonia increased in children with JIA and in the general population from 1999 to 2014. During 2007-2014 JIA patients had a significantly higher rate of pneumonia than age-matched controls. The use of active anti-rheumatic medication was common.

Severity of symptoms persists for decades in fibromyalgia-a 26-year follow-up study.

The aim of this study is to find out the outcome of 28 patients who got the diagnosis of primary fibromyalgia (pFM) 26 years ago. In 1986, 56 patients with widespread pain were examined and filled in a base questionnaire (BQ). Of them, 42 fulfilled the Yunus criteria for pFM. Twenty-six years later, addresses of 38 patients were found, and an extensive follow-up questionnaire (FupQ) was mailed to them. Of them, 28 (74%) answered the FupQ. This included nine identical questions with the BQ and questions concerning changes in their symptoms and quality of life (Qol). Three patients (11%) had healed from fibromyalgia (FM), and 23% reported having one or several symptomless periods lasting at least 1 year. In others (n = 25), all but pain and ache showed slight deterioration. Despite the aging and FM, the level of functional ability evaluated by Stanford Health Assessment Questionnaire (HAQ) remained at the same level (BQ 0.41 vs. Fup 0.44, p = 0.82). The sum score of reported symptoms (n = 21) did not change significantly (10.8 (SD 2.9) vs. 11.1 (SD 4.1), p = 0.75). Experienced sleeplessness increased most significantly (27 vs. 65%, p = 0.0034). Exercising did not have a significant influence on the changes of the measured parameters. However, the three healed patients exercised regularly. Symptoms of FM have persisted in most patients for decades without significant deterioration of self-reported functional ability. About one fourth of patients had experienced long symptomless periods during their illness. Three patients (11%) reported that they have healed from FM.

Somatic STAT3 mutations in Felty syndrome: an implication for a common pathogenesis with large granular lymphocyte leukemia.

Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome. Somatic STAT3 mutations were discovered in 43% (6/14) of Felty syndrome patients with deep amplicon sequencing targeting all STAT3 exons. Mutations were located in the SH2 domain of STAT3, which is a known mutational hotspot. No STAT5B mutations were found. In blood smears, overrepresentation of large granular lymphocytes was observed, and in the majority of cases the CD8+ T-cell receptor repertoire was skewed when analyzed by flow cytometry. In bone marrow biopsies, an increased amount of phospho-STAT3 positive cells was discovered. Plasma cytokine profiling showed that ten of the 92 assayed cytokines were elevated both in Felty syndrome and large granular lymphocyte leukemia, and three of these cytokines were also increased in patients with uncomplicated rheumatoid arthritis. In conclusion, somatic STAT3 mutations and STAT3 activation are as frequent in Felty syndrome as they are in large granular lymphocyte leukemia. Considering that the symptoms and treatment modalities are also similar, a unified reclassification of these two syndromes is warranted.

Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial.

OBJECTIVE: YKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission. METHODS: Ninety-nine patients with early DMARD-naïve RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay. RESULTS: At the baseline, plasma YKL-40 concentration was 57 ± 37 (mean ± SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-α antagonist infliximab was added on the combination treatment. CONCLUSIONS: High YKL-40 levels were found to be associated with disease activity in early DMARD-naïve RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission.

Epstein-Barr virus in peripheral blood is associated with response to rituximab therapy in rheumatoid arthritis patients.

Autoreactive B cells infected by Epstein-Barr virus (EBV) are suspected to be involved in the etiology of various human chronic autoimmune diseases. This motivated us to study the relationship between peripheral blood EBV load at baseline and treatment response to B cell-depleting therapy in rheumatoid arthritis (RA) patients. Thirty-five RA patients who started treatment with rituximab (RTX) in a routine clinical setting were assessed for baseline disease activity using disease activity score using 28 joint counts (DAS28) (erythrocyte sedimentation rate [ESR]). Treatment response was evaluated 3-7 months after RTX. EBV load in baseline whole blood (WB) samples was determined using quantitative PCR. EBV DNA was detected in 16/35 (46 %) of the WB samples. In these 16 EBV-positive patients, the median viral load was 3.15 (2.68-4.00) log copies/ml. Good/moderate European League Against Rheumatism (EULAR) response was observed in 16/16 of the EBV DNA-positive vs 13/19 EBV DNA-negative patients, p = 0.022. Significant response (DAS28 change >1.2) was observed in 14/16 of the EBV DNA-positive vs 10/19 EBV DNA-negative patients, p = 0.035. The decline in DAS28 after RTX was 2.10 (1.03-4. 78) in the EBV DNA-positive vs 1.47 (-0.7-4.70) in the EBV DNA-negative patients, p = 0.13. EBV load at baseline significantly correlated with change in DAS28 after RTX (τB = -0.261, p = 0.042). Our results suggest that the presence of EBV genome in WB could serve as a predictive marker to RTX therapy in RA.