Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib-A retrospective analysis on consecutive patients from a well-defined region.

OBJECTIVE: Ibrutinib treatment is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as increased risk of bleeding. Here, we aimed at describing the incidence of these events during long-term follow-up in patients with chronic lymphocytic leukemia treated outside clinical trials as well as identifying clinical factors predictive of developing AF. Additionally, other reasons for treatment withdrawal were analyzed. METHODS: The study was retrospective, data were collected from medical records. RESULTS: A total of 134 patients were identified. Median follow-up was 32 months (range 3-103) and median duration of ibrutinib treatment was 26 months (range 1-103). Of 110 patients with no prior history of AF, 24.5% were diagnosed during treatment. Newly diagnosed or worsening of pre-existing hypertension occurred in 15.7%. Sixty-six % of the patients experienced bleeding events, of which 7.5% grade 3-4. Treatment discontinuation and dose reduction occurred in 68% and 47% of the patients, respectively, mostly due to toxicity. CONCLUSIONS: The incidence of AF was high and at a median follow-up of 2.5 years, two-thirds of the patients discontinued treatment mostly due to bleeding and infections. Treatment-related toxicity of any grade should be regarded as a concern of prolonged ibrutinib therapy.

Health literacy in individuals with knee pain-a mixed methods study.

BACKGROUND: Low health literacy is associated with worse pain and poorer self-management. This study (1) examined the level of health literacy and associations with lifestyle habits, health status, chronic pain, and radiographic knee osteoarthritis; and (2) explored experiences illuminating health literacy among individuals with knee pain. METHODS: A convergent parallel mixed-methods design was used, including 221 individuals. Health literacy was assessed by HLS-EU-Q16 and eHEALS. The questionnaire included questions on lifestyle habits, health status, and pain distribution. Radiographic knee osteoarthritis was assessed with x-rays. Associations were analysed using logistic regression analyses. Individual semi-structured interviews were conducted (n = 19) and analysed with qualitative content analysis. RESULTS: The result showed that 71% reported sufficient health literacy. Higher education, healthy lifestyle habits, better general health, and absence of widespread pain were associated with sufficient health literacy. Experiences regarding health literacy influencing the decision-making process toward a decision on action comprised: (1) searching for information actively or passively; (2) processing of the information included being informed, critical, and interpretive; and (3) taking a stand on the information based on trustfulness and motivation. CONCLUSION: Seven out of 10 reported sufficient health literacy. Despite this, unhealthy lifestyles were common, suggesting that having sufficient HL is not enough for a behavioural change and the decision-making process, including different phases such as searching, processing, and taking a stand on health information is important to consider. More research on health literacy is needed to gain knowledge of how best to develop health promotion in individuals with knee pain.

Associations between chronic widespread pain, pressure pain thresholds, leptin, and metabolic factors in individuals with knee pain.

OBJECTIVE: The aim was to study associations between chronic widespread pain, widespread pain sensitivity, leptin, and metabolic factors in individuals with knee pain. A secondary aim was to study these associations in a subgroup of individuals with normal BMI. METHOD: This cross-sectional study included 265 individuals. The participants were categorised into three different pain groups: Chronic widespread pain (CWP), chronic regional pain (ChRP), or no chronic pain (NCP). The pressure pain thresholds (PPTs) were assessed using computerised pressure algometry. Low PPTs were defined as having PPTs in the lowest third of all tender points. Leptin and metabolic factors such as BMI, visceral fat area (VFA), lipids, and glucose were also assessed. RESULT: Sixteen per cent reported CWP, 15% had low PPTs, and 4% fulfilled both criteria. Those who fulfilled the criteria for CWP were more often women, more obese, and had increased leptin levels. In logistic regression, adjusted for age and gender, leptin was associated with fulfilling criteria for CWP, OR 1.015 (95% CI 1.004-1.027, p = 0.008). In logistic regression, adjusted for age and gender, leptin was associated with low PPTs, OR 1.016 (95% CI 1.004-1.029, p = 0.012). Leptin was also associated with fulfilling both criteria, adjusted for age, sex, and visceral fat area (VFA), OR 1.030 (95% CI 1.001-1.060), p = 0.040. CONCLUSION: Leptin was associated with fulfilling the combined criteria for chronic widespread pain and low PPTs, even after adjusting for the visceral fat area (VFA). Longitudinal studies are needed to study the causal relationships between leptin and the development of widespread pain. TRIAL REGISTRATION: clinicalTrials.gov Identifier: NCT04928170.

Pressure pain thresholds in individuals with knee pain: a cross-sectional study.

BACKGROUND: Knee osteoarthritis (KOA), chronic widespread pain (CWP) and overweight/obesity are public health problems that often coincide, and there is a multifactorial and unclear relationship between them. The study aimed to (1) investigate pain sensitivity, assessed by pressure pain thresholds (PPTs), among women and men with knee pain and (2) associations with, respectively, radiographic KOA (rKOA), CWP, and overweight/obesity. METHODS: Baseline data from an ongoing longitudinal study involving 280 individuals with knee pain in the 30-60 age group. Pain sensitivity was assessed by PPTs on eight different tender points using a pressure algometer. The participants' knees were x-rayed. Self-reported CWP and number of pain sites were assessed with a pain figure, and overweight/obesity was measured using body mass index (BMI), visceral fat area (VFA), and body fat percentage, assessed with a bioimpedance. Associations were analysed using regression analyses. RESULTS: Women reported lower PPTs than men (p < 0.001), but no PPTs differences were found between those with and without rKOA. Low PPTs was associated with female sex, more pain sites, CWP, and a higher VFA and body fat percentage. The tender points second rib and the knees were most affected. The prevalence of CWP was 38 %. CONCLUSIONS: The modifiable factors, increased VFA, and body fat could be associated with increased pain sensitivity among individuals with knee pain. Longitudinal studies are needed to further investigate the associations.

Chronic widespread pain and its associations with quality of life and function at a 20- year follow-up of individuals with chronic knee pain at inclusion.

OBJECTIVE: To study the prevalence of chronic widespread pain (CWP) and chronic regional pain (CRP), and their association to quality of life, pain, physical function at a 20-year follow-up in a population based cohort with chronic knee pain at inclusion. METHODS: 121 individuals (45% women, mean age 64 years, range 54-73) with chronic knee pain from a population-based cohort study, answered a questionnaire and had radiographic knee examination at a 20-year follow-up. The responders were divided into three groups according to reported pain; individuals having no chronic pain (NCP), chronic widespread pain (CWP) and chronic regional pain (CRP). Pain and physical function were assessed using Knee injury and Osteoarthritis Outcome Score (KOOS). Health related quality of life (HRQL) was assessed with Euroqol-5D-3 L (EQ5D) and Short form 36 (SF36). The associations between pain groups and KOOS, EQ5D, and SF36 were analysed by multiple logistic regression, controlled for age, gender and radiographic changes indicating knee osteoarthritis (OA). RESULTS: The prevalence of CWP was 30%, and CWP was associated to worse scores in all KOOS subscales, controlled for age, gender and radiographic changes. CWP was also associated to worse scores in EQ-5D and in seven of the SF-36 subgroups, controlled for age, gender and radiographic changes. CONCLUSION: One third of individuals with chronic knee pain met the criteria for CWP. CWP was associated with patient reported pain, function and HRQL. This suggest that it is important to assess CWP in the evaluation of patients with chronic knee pain, with and without radiographic knee OA.

Development of radiographic knee osteoarthritis and the associations to radiographic changes and baseline variables in individuals with knee pain: a 2-year longitudinal study.

OBJECTIVES: The aim was to study the development of radiographic knee osteoarthritis (RKOA) in individuals with knee pain over 2 years, and the associations between radiographic changes and baseline variables. DESIGN: Longitudinal cohort study. PARTICIPANTS AND SETTING: This study is part of the Halland Osteoarthritis cohort. The included 178 individuals, aged 30-67, had knee pain, without cruciate ligament injury or radiographic findings and 67% were women. The presence of RKOA was defined as Ahlbäck score of ≥1 in ≥1 knee. (Ahlbäck grade 1: joint space narrowing in the tibiofemoral joint <3 mm). Diagnosis of clinical KOA was based on the clinical guideline from the National Institute for Health and Care Excellence (NICE). Knee injury and Osteoarthritis Outcome Score (KOOS), pain intensity, physical function, body mass index (BMI) and visceral fat area (VFA) were measured. Associations to RKOA were analysed with logistic regression (OR). RESULTS: In all, 13.8% (n=24) developed RKOA in 2 years whereof all had clinical KOA at baseline, as defined by NICE. Deterioration to RKOA was significantly associated with higher BMI, OR 1.119 (95% CI 1.024 to 1.223; p=0.013), and VFA, 1.008 (95% CI 1.000 to 1.016; p=0.049), worse knee pain intensity, 1.238 (95% CI 1.028 to 1.490; p=0.024), worse scores for KOOS Pain, 0.964 (95% CI 0.937 to 0.992; p=0.013) and KOOS Symptoms, 0.967 (95% CI 0.939 to 0.996; p=0.027), KOOS Activities of daily living 0.965 (95% CI 0.935 to 0.996; p=0.026) and KOOS Quality of Life 0.973 (95% CI 0.947 to 0.999; p=0.044), at baseline. CONCLUSIONS: One out of seven individuals with clinical KOA developed RKOA in only 2 years. Baseline variables associated with RKOA after 2 years may possibly be detected early by using the NICE guideline, assessment of obesity and self-reported data of symptoms to support first-line treatment: education, exercise and weight control. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04928170).

Alcohol consumption is associated with lower self-reported disease activity and better health-related quality of life in female rheumatoid arthritis patients in Sweden: data from BARFOT, a multicenter study on early RA.

BACKGROUND: Earlier studies have found a positive effect of alcohol consumption, with a reduced disease activity in rheumatoid arthritis (RA). The aim of this study was to assess alcohol consumption and its association with disease activity and health related quality of life (HRQL) in Swedish RA patients. METHODS: Between 1992 and 2005, 2,800 adult patients were included in the BARFOT study of early RA in Sweden. In 2010 a self-completion postal questionnaire was sent to all 2,102 prevalent patients in the BARFOT study enquiring about disease severity, HRQL, and lifestyle factors. Alcohol consumption was assessed using the validated AUDIT-C questionnaire. RESULTS: A total of 1,238 out of 1,460 patients answering the questionnaire had data on alcohol consumption: 11% were non-drinkers, 67% had a non-hazardous drinking, and 21% were classified as hazardous drinkers. Women who drank alcohol reported lower disease activity and better HRQL, but there were no association between alcohol consumption and disease activity in men. For current smokers, alcohol use was only associated with fewer patient-reported swollen joints. The outcome was not affected by kind of alcohol consumed. CONCLUSIONS: There was an association between alcohol consumption and both lower self-reported disease activity and higher HRQL in female, but not in male, RA patients.

Early increase in serum-COMP is associated with joint damage progression over the first five years in patients with rheumatoid arthritis.

BACKGROUND: Currently available biomarkers for the early tissue process leading to joint damage in rheumatoid arthritis are insufficient and lack prognostic accuracy, possibly a result of variable activity of the disease over time. This study represents a novel approach to detect an altered activity of the disease process detected as increasing serum-COMP levels over a short time and whether this would correlate with joint damage progression over the first 5 years of disease. METHODS: In all, 349 patients from the Swedish BARFOT early RA study were examined. Serum-COMP was analysed by ELISA at diagnosis and after 3 months. Based on changes in serum-COMP levels, three subgroups of patients were defined: those with unchanged levels (change ≤ 20%) (N=142), decreasing levels (> 20%) (N=173) and increasing levels (> 20%) (N=34). Radiographs of hands and feet were obtained at inclusion, after 1, 2 and 5 years and scored according to Sharp van der Heijde (SHS). Radiographic progression was defined as increase in SHS by ≥5.8. RESULTS: The group of patients with increasing COMP levels showed higher median change in total SHS and erosion scores at 1, 2 and 5 year follow-up compared with the groups with stable or decreasing COMP levels. Furthermore, the odds ratio of radiographic progression was 2.8 (95% CI 1.26-6.38) for patients with increasing COMP levels vs. patients with unchanged levels.The group of patients with increasing COMP levels had higher ESR at inclusion but there were no baseline differences between the groups for age, gender, disease duration, disease activity (DAS28), function (HAQ), CRP, nor presence of rheumatoid factor or anti-CCP. Importantly, neither did changes over the 3-month period in DAS28, HAQ, ESR nor CRP differ between the groups and these variables did not correlate to joint damage progression. CONCLUSION: Increasing serum-COMP levels between diagnosis and the subsequent 3 months in patients with early RA represents a novel indicator of an activated destructive process in the joint and is a promising tool to identify patients with significant joint damage progression during a 5-year period.

The effect of snuff (smokeless tobacco) on disease activity and function in rheumatoid arthritis: experiences from the Better Anti-Rheumatic FarmacOTherapy, a longitudinal multicenter study on early rheumatoid arthritis.

BACKGROUND: It is not known whether snuff (moist smokeless tobacco) affects disease activity in rheumatoid arthritis (RA). OBJECTIVE: This study aims to study the effect of snuff on disease activity and function in Swedish patients with early RA. METHODS: Between 1992 and 2005, 2800 adult patients were included in the Better Anti-Rheumatic FarmacOTherapy (BARFOT) early RA study in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire, visual analog scale for general health, and drug treatment were registered at inclusion and at follow-up after 1, 2, and 5 years. European League Against Rheumatism response and remission criteria were applied at 1 year. In 2010, a self-completed postal questionnaire was sent to 2102 patients in the BARFOT study enquiring about lifestyle factors such as smoking and use of snuff. Three controls for each patient using snuff were identified. RESULTS: Fifty-one patients who used snuff were identified, together with 145 controls. When we adjusted for socioeconomic class, disease duration, and previous antirheumatic medication, the snuff users had lower DAS28 values at up to 6 months of follow-up than patients who had never smoked, and they had lower DAS28 values than previous smokers at up to 2 years of follow-up. No effect of snuff use on European League Against Rheumatism response was seen at up to 1 year. CONCLUSIONS: Snuff users initially had lower DAS28 levels than never smokers and previous smokers.

The effect of a tight control regime with monthly follow-up on remission rates and reported pain in early rheumatoid arthritis.

OBJECTIVE: To determine whether a tight control (TC) regime with monthly consultations to the physician for the first 6 months, could increase remission rate and improve reported pain of patients with early rheumatoid arthritis (RA). METHODS: In this single-centre, TC study, with monthly visits to the physician, a cohort of 100 patients with early RA was consecutively included. They were compared with a reference cohort of 100 patients from the same clinic that had been conventionally managed. The patients were followed for 2 years. RESULTS: The patients in the TC cohort had lower 28- joints disease activity score (DAS28) at three, six, 12 and 24 months, compared with the conventionally managed cohort, p ≤ 0.001. At 12 months, 71% in the TC cohort versus 46% in the conventional cohort were in remission (DAS28 < 2.6) and at 24 months 68% versus 49% respectively, p < 0.05. The TC cohort reported less pain at three, six, 12 and 24 months, p < 0.001. Multiple logistical regression analyses adjusted for, respectively, age, disease duration, pharmacological treatment, DAS28 and visual analogue scale pain at inclusion, revealed that participation in the TC cohort had an independent positive association with remission at 12 and 24 months and with acceptable pain at 24 months. CONCLUSION: The intensive follow-up schedule for patients with early RA improved remission and led to improvement in reported pain and physical function. The positive effect of a TC regime in early disease may be due to increased empowerment, developed by meeting health professionals frequently.

Autoantibodies to Disease-Related Proteins in Joints as Novel Biomarkers for the Diagnosis of Rheumatoid Arthritis.

OBJECTIVE: This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints. METHODS: We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead-based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age- and sex-matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE). RESULTS: Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98-100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19-26%) of early RA patients seronegative for anti-cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE. CONCLUSION: A multiplex immunoassay with peptides from disease-related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA.

Is knee osteoarthritis a symmetrical disease? Analysis of a 12 year prospective cohort study.

BACKGROUND: The aim of this study was to document the development of bilateral knee osteoarthritis over a 12 year period using a middle-aged population-based cohort with knee pain at inclusion. METHODS: One hundred and forty three patients aged 35 to 54 were recruited from a population based cohort of 279 subjects who had knee pain at baseline and assessed with clinical and radiographic data, with 5 and 12 year follow up. The data was analysed with regard to the development and progression of uni- and bilateral knee osteoarthritis over 12 years. A definition of KL = 1 was used to define radiographic disease. RESULTS: 24 of the 30 (80%) patients with unilateral disease at baseline developed bilateral disease after 12 years. At baseline 37 patients (26%) had bilateral disease, whereas that number increased to 65 (52%) at 5 years and 100 (70%) at the 12 year follow up. The most common pattern was medial compartment involvement in both knees. Six patients had lateral compartment disease in one knee and medial in the other whereas only two had lateral compartment disease bilaterally. CONCLUSIONS: Bilateral knee osteoarthritis is very common with time, as the majority of sufferers will eventually develop radiographic disease in both knees. Clinicians need to be aware of the 'joint at risk' and researchers need to remember to account for both knees when assessing the relationship between physical function, pain and structural disease. The other knee should not be used for comparison, even if it appears to be normal at baseline.

Experiences of How Health and Lifestyle among Individuals with Knee Pain Have Been Influenced during the COVID-19 Pandemic, a HALLOA Study.

The COVID-19 pandemic has affected the health and lifestyles of both the general population and of vulnerable groups. Individuals with knee pain are recommended to lead an active lifestyle to relieve pain but find it difficult to maintain health and lifestyle compared to the general population due to the cause of chronic pain, impaired physical function, and a diminished quality of life. This study aimed to explore experiences of how health and lifestyle among individuals with knee pain have been influenced during the COVID-19 pandemic. Interviews (n = 19) were conducted in 2021 and analysed with qualitative content analysis. The results showed how individuals with knee pain adjusted their behaviour and revalued their life to maintain health and lifestyle during COVID-19. Adjusted behaviours emerged, such as spending more time at home, becoming digital, and spending more time outdoors, while revaluing life emerged as having a positive outlook on life and sharing responsibility. In conclusion, behaviour was adjusted, and life revalued to manage health and lifestyle during the pandemic. However, the findings are probably similar to the general population, i.e., individuals with knee pain live similar lives as the general population despite knee pain. The results may contribute to alternative ways of maintaining health and lifestyle in various vulnerable groups and may be applied in situations other than the pandemic.

Lifestyle factors in patients with rheumatoid arthritis-a cross-sectional study on two Scandinavian cohorts.

INTRODUCTION: The risk for cardiovascular diseases and other comorbidities increases with the number of unhealthy lifestyle factors in the general population. However, information on the combined number of unhealthy lifestyle factors in people with rheumatoid arthritis (RA) is scarce. OBJECTIVES: To study lifestyle factors and the association between disease impact and two or more unhealthy lifestyle factors in two Scandinavian cohorts with RA. METHODS: We analysed data from two cohorts, Danish (n = 566; mean age 61.82 (SD 11.13) years; 72% women) and Swedish (n = 955; mean age 66.38 (SD 12.90) years; 73% women). Lifestyle factors (tobacco use, BMI, alcohol consumption and physical activity) were dichotomised as healthy vs. unhealthy (range 0-4 unhealthy factors). The association between disease impact and two or more unhealthy lifestyle factors was analysed using logistic regression. RESULTS: Sixty-six percent of Danish and 47% of Swedish respondents reported two or more unhealthy lifestyle factors, most commonly, being overweight/obese and physical inactivity. For Danish participants, two or more unhealthy lifestyle factors were associated with (OR and 95% CI) male gender (1.86; 1.21-2.85), cardiovascular diseases (1.90; 1.28-2.82) and disease duration (0.97; 0.95-0.99). Corresponding findings for the Swedish cohort were male gender (1.42; 1.07-1.89), pain (1.10; 1.04-1.15), fatigue (1.09; 1.04-1.15), physical functioning (1.64; 1.28-2.10) and quality of life (0.35; 0.20-0.60). CONCLUSION: Many patients, most often male, in both cohorts had two or more unhealthy lifestyle factors. The number of unhealthy lifestyle factors indicates a multifaceted relationship with disease impact.

Cohort profile: the Halland osteoarthritis (HALLOA) cohort-from knee pain to osteoarthritis: a longitudinal observational study in Sweden.

PURPOSE: The overall objective in this study is to investigate the early development of radiographic knee osteoarthritis (OA) and its association with hand or/and knee OA, metabolic diseases, biomarkers, chronic pain, physical function and daily physical activity types. PARTICIPANTS: The Halland osteoarthritis (HALLOA) cohort is a longitudinal cohort study that includes individuals with knee pain in the southwest of Sweden. Enrolment took place from 2017 to 2019. The inclusion criteria were current knee pain, with no former known radiographic knee OA and no cruciate ligament rupture or rheumatological disorder. The participants were recruited: (1) when seeking care for knee pain in primary healthcare or (2) by advertisements in local newspapers. There are 306 individuals included in the study, mean age (SD) 51.7 (8.7) years and 69% are women. The baseline and follow-ups include clinical tests, radiographical examinations, blood samples, metabolic measures, pain pressure thresholds, tests of physical functions, daily physical activity types and patient-reported outcomes. FINDINGS TO DATE: There were associations between metabolic factors and radiographic knee OA, even in those with normal body mass index at baseline. In addition, clinical hand OA was positively associated with fasting plasma glucose. We also found that modifiable factors as increased visceral fat and total body fat were associated with increased pain sensitivity among individuals with knee pain. FUTURE PLANS: By studying possible pathophysiological mechanisms of OA over time, we aim to provide new insights on OA progression, identify usable preventive measures helping the clinicians in the management of the disease and improve health for the patients. It is also important to study the development of chronic pain in OA, to get tools to identify individuals at risk and to be able to offer them treatment. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04928170).

Experiences of Health-Promoting Activities among Individuals with Knee Pain: The Halland Osteoarthritis Cohort.

Knee pain is an early sign of knee osteoarthritis (KOA) and a risk factor for chronic widespread pain (CWP). Early prevention is vital, and more research is needed to understand health-promoting activities for individuals with knee pain from a patient perspective. This study aimed to explore how individuals with knee pain experienced health-promoting activities. Explorative qualitative design with inductive approach was applied to explore the experiences of 22 individuals (13 women, 9 men; median age: 52). Semi-structured interviews were conducted and analysed using latent qualitative content analysis. The results revealed health-promoting activities in individuals with knee pain and were interpreted in the overall theme, striving for balance in everyday life. Two categories explored the content in health-promoting activities: (1) Caring for the body-being physically active, having a healthy diet, and utilising support; and (2) Managing life stressors-allowing for recovery, promoting vitality, and safeguarding healthy relationships. In conclusion, individuals with knee pain described various health-promoting activities. They strived for balance in everyday life by caring for the body and managing life stressors. We suggest that a broader approach to everyday life can be helpful in treatment plans and health promotion to manage and prevent KOA and CWP, while striving for a healthy lifestyle.

Erosion-free rheumatoid arthritis: clinical and conceptional implications-a BARFOT study.

BACKGROUND: Bone erosions may appear early or later during rheumatoid arthritis (RA), causing joint damage and functional impairment. However, in some patients erosions do not occur, even after several years of disease. This study evaluates the prevalence, clinical relevance and possible predictors of erosion-free RA. METHODS: Six hundred and eight patients from an early RA cohort (BARFOT) having radiographs of hands and feet at inclusion and after 1, 2, 5 and 8 years were studied. Clinical and functional assessments were performed on all these time-points. RESULTS: In all, 144 patients (24%) did not develop erosions up to 8 years follow-up (Never erosive group), while 464 patients (76%) had erosions on one or more assessments (Ever erosive group). At diagnosis, the patients in the Never erosive group were significantly younger, satisfied fewer ACR criteria, and were less frequently RF- and/or anti-CCP- positive compared with those in the Ever erosive group. The Never erosive patients had consistently more tender joints, lower erythrocyte sedimentation rate (ESR) and, from two years and onwards, fewer swollen joints. Absence of rheumatoid factor (RF) and/or anti-CCP were strong independent predictors for erosion-free disease. The erosion-free patients were less frequently treated with DMARDs and/or prednisolone. CONCLUSIONS: One-quarter of the patients was erosion-free during eight years in this early RA cohort. Erosion-free patients had a less severe disease course as to disease activity and were more often seronegative compared with those with erosive disease. The results suggest that non-erosive RA represents a milder form of RA.

Immune Biomarkers in the Peripheral Blood and Tumor Microenvironment of Classical Hodgkin Lymphoma Patients in Relation to Tumor Burden and Response to Treatment.

In classical Hodgkin lymphoma (cHL), the malignant cells represent only a small fraction of the tumor. Yet, they orchestrate a lymphocyte-dominated tumor microenvironment (TME) that supports their survival and growth. The systemic effects of this local immunomodulation are not fully elucidated. Here, we aimed at characterizing circulating lymphocytes and plasma proteins in relation to clinical parameters and treatment effect. Peripheral blood (PB) samples were obtained from 48 consecutive patients at diagnosis and at 2 time points after successful primary treatment. Single-cell suspensions were prepared from lymph node (LN) biopsies obtained for routine diagnostic purposes. Twenty healthy individuals were included as controls. Cells from PB and LN were analyzed by flow cytometry, and plasma proteins by Proximity Extension Assay. We found that the frequencies of T and B cells positively correlated between the LN and the PB compartments. Compared to controls, cHL patients had higher frequencies of proliferating T cells as well as higher expression of programmed death (PD)-1 and cytotoxic T lymphocyte antigen (CTLA)-4 in circulating T cells, and lower naive T-cell frequencies. Advanced-stage patients had fewer NK cells with a functionally impaired phenotype. Differences in the immune profile were observed in patients with a high tumor burden and with high inflammation, respectively. Most of these deviations disappeared after standard first-line treatment. Patients who received radiotherapy involving the mediastinum had low T-cell counts for a prolonged period. Our findings suggest that the immunomodulation of lymphocytes in the TME of cHL might affect immune biomarkers in the PB.

Distribution of erosions in hands and feet at the time for the diagnosis of RA and during 8-year follow-up.

BACKGROUND: Joint destruction in rheumatoid arthritis (RA) is usually evaluated by radiographs of both hands and feet, while the inflammatory status mostly is evaluated by DAS28 which, however, does not include the feet. OBJECTIVES: To investigate the distribution of erosions in hands and feet in early RA over 8 years and its potential clinical implications. Furthermore, the group of patients never showing erosions has been addressed. METHODS: This study comprises 1041 patients from the BARFOT study of patients with early RA. Radiographs of hands and feet were performed at baseline, 1, 2, 5, and 8 years and evaluated by the Sharp van der Heijde scoring (SHS) method (32 joints in the hands and 12 in the feet). Disease activity was measured by DAS28, SR, CRP, and function with HAQ. RESULTS: In the feet, there were significantly more eroded joints in percent of examined joints than in the hands at all time points. Patients with erosions only in the feet were younger, more often seropositive and smokers. They had significantly lower baseline DAS28, than the patients with erosions only in the hands. The patients without erosions over time were, at diagnosis, significantly younger and less frequently seropositive compared with patients having erosions. CONCLUSIONS: This study highlights the importance of evaluating the feet in patients with RA, both with clinical examinations and with imaging and lends support to the notion that seropositivity and smoking are risk factors for erosive disease. Further studies of patients with nonerosive disease are needed. KEY POINTS: • Foot problems are common in RA • This study emphasizes the limitations of DAS28 and Sharp van der Heijde score as regards evaluating disease activity and radiographic damage • This study highlights the importance of evaluating the feet in patients with RA with clinical examinations and imaging • This study also points out the need of further studies of patients with non-erosive RA.

Higher levels of anti-phosphorylcholine autoantibodies in early rheumatoid arthritis indicate lower risk of incident cardiovascular events.

BACKGROUND: The increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA. METHODS: The study population was derived from the BARFOT early RA cohort, recruited in 1994-1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC. RESULTS: In all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded. Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142-0.916); in males, HR 0.558 (0.325-0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065-0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379-0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years. CONCLUSION: Protective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.