Nationwide, large-scale implementation of an online system for remote entry of patient-reported outcomes in rheumatology: characteristics of users and non-users and time to first entry.

AIMS: In May 2020, a nationwide, web-based system for remote entry of patient-reported outcomes (PROs) in inflammatory rheumatic diseases was launched and implemented in routine care (DANBIO-from-home). After 1.5 years of use, we explored clinical characteristics of patients who did versus did not use the system, and the time to first entry of PROs. METHODS: All patients followed in DANBIO were informed about DANBIO-from-home by electronic invitations or when attending their clinic. Characteristics of patients who did/did not use DANBIO-from-home in the period after implementation were explored by multivariable logistic regression analyses including demographic and clinical variables (gender, age group, diagnosis, disease duration, use of biological disease-modifying agent (bDMARD), Health Assessment Questionnaire (HAQ), Patient Acceptable Symptom Scale (PASS)). Time from launch to first entry was presented as cumulative incidence curves by age group (<40/40-60/61-80/>80 years). RESULTS: Of 33 776 patients, 68% entered PROs using DANBIO-from-home at least once. Median (IQR) time to first entry was 27 (11-152) days. Factors associated with data entry in multivariate analyses (OR (95% CI)) were: female gender (1.19 (1.12 to 1.27)), bDMARD treatment (1.41 (1.33 to 1.50)), age 40-60 years (1.79 (1.63 to 1.97)), 61-80 years (1.87 (1.70 to 2.07), or age >80 years (0.57 (0.50 to 0.65)) (reference: age <40 years), lower HAQ (0.68 (0.65 to 0.71)) and PASS 'no' (1.09 (1.02 to 1.17). Diagnosis was not associated. Time to first entry of PROs was longest in patients <40 years of age (119 (24-184) days) and shortest in the 61-80 years age group (25 (8-139) days). CONCLUSION: A nationwide online platform for PRO in rheumatology achieved widespread use. Higher age, male gender, conventional treatment and disability were associated with no use.

Long-term Behavioral Changes During the COVID-19 Pandemic and Impact of Vaccination in Patients With Inflammatory Rheumatic Diseases.

OBJECTIVE: To explore anxiety and self-isolation in patients with inflammatory rheumatic disease (IRD)15 months into the coronavirus disease 2019 (COVID-19) pandemic, including attitudes toward and effects of SARS-CoV-2 vaccination. METHODS: A nationwide online survey was conducted at 3 timepoints: May 2020, November 2020, and May 2021. Patients with IRD followed in the Danish Rheumatology Quality Registry (DANBIO) were asked about the effects of the pandemic, including SARS-CoV-2 infection and their behavior, anxiety, and concerns. The May 2021 survey included attitudes toward SARS-CoV-2 and influenza vaccination. Characteristics associated with self-isolation in May 2021 were explored with adjusted logistic regression analyses that included patient characteristics and SARS-CoV-2 vaccination status. RESULTS: Respondents to surveys 1, 2, and 3 included 12,789; 14,755; and 13,921 patients, respectively; 64% had rheumatoid arthritis and 63% were female. Anxiety and concerns were highest in May 2020 and decreased to stable levels in November 2020 and May 2021; 86%, 50%, and 52% of respondents reported self-isolation, respectively. In May 2021, 4% of respondents self-reported previous SARS-CoV-2 infection. The SARS-CoV-2 vaccine acceptance rate was 86%, and the proportion of patients vaccinated against influenza had increased from 50% in winter 2019-2020 to 64% in winter 2020-2021. The proportion of patients with anxiety appeared similar among those vaccinated and unvaccinated against SARS-CoV-2. In multivariable analyses, being unvaccinated, female gender, receiving biologic drugs, and poor quality of life were independently associated with self-isolation. CONCLUSION: Levels of anxiety and self-isolation decreased after the initial lockdown period in patients with IRD. Half of the patients reported self-isolation in May 2021, a phase that included widespread reopening of society and large-scale vaccination. The lack of prepandemic data prevented a full understanding of the long-term effects of the pandemic on anxiety and self-isolation in patients with IRD.

Impact of the COVID-19 pandemic on treat-to-target strategies and physical consultations in >7000 patients with inflammatory arthritis.

OBJECTIVES: To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease. METHODS: Patients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment). RESULTS: We included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21-72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%). CONCLUSION: In this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

Fast track clinic for early diagnosis of polymyalgia rheumatica: Impact on symptom duration and prednisolone initiation.

OBJECTIVES: To evaluate the efficacy of a fast track clinic (FTC) for patients suspected of polymyalgia rheumatica (PMR) regarding symptom duration, prednisolone initiation before rheumatological assessment, number of hospital contacts before diagnosis, and cancer diagnosis. METHODS: It is a retrospective cohort study with a one year follow-up period. Patients referred to the FTC (1st August 2016 to 25th June 2019) were compared to a historical cohort of PMR patients (1st August 2014 to 1st August 2016). Referral criteria are: age over 50, symptoms of PMR but not cranial GCA, and increased C-reactive protein. Data were obtained from patient journals. RESULTS: Ninety-seven PMR patients in the historical cohort and 113 FTC patients, of whom 83 patients had PMR, were included. The median (interquartile range) number of days from symptom onset until PMR diagnosis were 53 (31-83) days in the FTC versus 80 (58-132) days in the historical cohort (P<0.001). Prednisolone was prescribed before rheumatological assessment to 11% in the FTC versus 42% in the historical cohort (P<0.001). Patients in the FTC had significantly fewer contacts with the hospital before the diagnosis compared with the historical cohort. Four patients in the FTC were diagnosed with a cancer, all of which were found by imaging. CONCLUSION: The FTC reduced the time from symptom onset until diagnosis, lowered prednisolone initiation before rheumatological assessment, and resulted in fewer hospital visits. The frequency of cancers was low in patients suspected of PMR and cancers were discovered by imaging.

Self-protection strategies and health behaviour in patients with inflammatory rheumatic diseases during the COVID-19 pandemic: results and predictors in more than 12 000 patients with inflammatory rheumatic diseases followed in the Danish DANBIO registry.

AIMS: In Danish patients with inflammatory rheumatic diseases to explore self-protection strategies and health behaviour including adherence to disease-modifying antirheumatic treatment (DMARD) during the initial phase of the COVID-19 pandemic and again after the reopening of the society started. Furthermore, to identify characteristics of patients with high levels of anxiety and self-isolation. METHODS: Patients in routine care followed prospectively in the nationwide DANBIO registry were invited to answer an online questionnaire regarding disease activity and COVID-19 infection, behaviour in March and June 2020. Responses were linked to patient data in DANBIO. Characteristics potentially associated with anxiety, self-isolation and medication adherence (gender/age/diagnosis/education/work status/comorbidity/DMARD/smoking/EQ-5D/disease activity) were explored with multivariable logistic regression analyses. RESULTS: We included 12 789 patients (8168 rheumatoid arthritis/2068 psoriatic arthritis/1758 axial spondyloarthritis/795 other) of whom 65% were women and 36% treated with biological DMARD. Self-reported COVID-19 prevalence was 0.3%. Patients reported that they were worried to get COVID-19 infection (March/June: 70%/45%) and self-isolated more than others of the same age (48%/38%). The fraction of patients who changed medication due to fear of COVID-19 were 4.1%/0.6%. Female gender, comorbidities, not working, lower education, biological treatment and poor European Quality of life, 5 dimensions were associated with both anxiety and self-isolation. CONCLUSION: In >12 000 patients with inflammatory arthritis, we found widespread anxiety and self-isolation, but high medication adherence, in the initial phase of the COVID-19 pandemic. This persisted during the gradual opening of society during the following months. Attention to patients' anxiety and self-isolation is important during this and potential future epidemics.

[Inflammatory spinal arthritis].

Spondyloarthritis (SpA) is an inflammatory arthritis mainly affecting the axial skeleton and large peripheral joints. Age of onset is typically 20-35 years. However, symptoms of SpA is often overlooked or interpreted as common low back pain, postponing an effective treatment. In this review, symptoms of SpA with emphasis on inflammatory pain and clinical findings are summed-up. Furthermore, diagnostic challenges, and treatments are covered.

Incidence of Free of Charge Physiotherapy in a Danish National Cohort of Stroke, Parkinson's Disease, Multiple Sclerosis and Rheumatoid Arthritis Patients.

BACKGROUND: Denmark is a welfare state with a publically funded healthcare system that includes the right to free of charge physiotherapy (FCP) for patients with chronic or progressive disease who fulfill strict criteria. The aim of this study was to investigate the incidence of referral to FCP in patients with a hospital diagnosis of stroke, multiple sclerosis (MS), Parkinson's disease (PD) and rheumatoid arthritis (RA) between 2007 and 2016. METHODS: The study was register-based and included data from The Danish National Patient Registry and The National Health Service Registry. The study population included the four largest disease groups receiving FCP in Denmark. The incidence of receiving FCP was reported as the cumulated incidence proportion (CIP). RESULTS: The study showed that FCP was mainly initiated within the first 2 years after diagnosis. The 2-year CIP was 8% for stroke patients, 53% for PD patients, 49% for MS patients, and 16% for RA patients. The proportion of patients referred to FCP generally increased over the period of the study due to more patients being referred from medical specialists in primary care. CONCLUSION: This study found substantial differences in the incidence of referral to FCP in a Danish population of stroke, PD, MS and RA patients.

CT-guided transarticular biopsy of the sacroiliac joint: Technique and histomorphological results. A preliminary study.

OBJECTIVE: To introduce and evaluate computed tomography (CT)-guided transarticular needle biopsy of the cartilaginous sacroiliac joint (SIJ) and to assess the biopsy results microscopically. MATERIALS AND METHODS: The new CT-guided transarticular biopsy of the SIJ was performed in a young corpse and ten patients, two males and eight females aged 18-81 years. All patients had abnormal findings by magnetic resonance imaging (MRI) of the SIJs, including bone marrow edema, related to different types of joint disorders. The biopsies were focused on areas with bone marrow edema. The quality of the specimens obtained, using two different types of biopsy needles, was assessed microscopically. RESULTS: Biopsies containing cartilage, subchondral plate, and bone marrow from the iliac and sacral sides were obtained from the corpse and three patients and from the iliac bone only in two patients. In three patients, the biopsy needles could not penetrate the bone marrow to the joint facet due to pronounced subchondral sclerosis, but adequate marrow biopsies were obtained. Two biopsies were inadequate, one due to technical problems and one was crushed during preparation. Histological assessment of eight adequate specimens revealed inflammatory bone marrow changes, except in two specimens from females with pronounced sclerosis conforming to osteitis condensans ilii. CONCLUSIONS: Transarticular SIJ biopsies are obtainable and can be directed towards areas with MRI abnormalities. They can be used to confirm inflammatory changes histologically. With the biopsy needles used, severe bone marrow sclerosis may hinder penetration to the cartilage, but bone marrow specimens can be obtained.

Anti-tumor necrosis factor treatment increases both the Th17 and Th22 T helper subsets in spondyloarthritis.

The aim was to examine anti-tumor necrosis factor α (anti-TNFα) therapy influence changes on Th17 and Th22 cells in patients with spondyloarthritis (SpA), and its correlation with changes in clinical and magnetic resonance imaging (MRI) activity and chronicity scores. The Th17 and Th22 cells were assessed at baseline, after 12 and 52 weeks of anti-TNFα therapy by flow cytometry (ClinicalTrials.gov NCT4682724). The percentages of both Th17 and Th22 cells were increased by 70% at baseline compared with healthy controls (both p < 0.01). During treatment, these two subsets increased further to be 170% (Th17) and 123% (Th22) above levels in healthy controls (both p < 0.01). The same subsets decrease their expression of IL-23R significantly during the observation period (p < 0.05). High levels of Th17 and Th22 cells at baseline were associated with the degree of chronic changes in the sacroiliac joints on MRI and a good clinical response to anti-TNFα treatment after one year. Plasma levels were not associated with clinical changes. Th17 cells, and Th22 subsets, increased during one year of anti-TNF-α therapy in SpA, regardless of their clinical improvement. This supports that both the Th17 and Th22 subsets could be involved in the progression in SpA.

Probiotics for chronic low back pain with type 1 Modic changes: a randomized double-blind, placebo-controlled trial with 1-year follow-up using Lactobacillus Rhamnosis GG.

PURPOSE: To investigate whether treatment by lactic acid bacteria for 100 days is associated with change of disability and pain in chronic low back pain (CLBP) patients with type 1 or mixed Modic changes (MC) during 1-year follow-up. METHODS: Eighty-nine patients with CLBP and type 1 MC or mixed MC were randomized to receive either one capsule Lactobacillus Rhamnosis GG (6 billion colony-forming unit per capsule) twice daily or placebo capsules for 100 days. RESULTS: Missing values at 1 year were 4% and 3% in the disability and pain variables, respectively. The predefined outcomes disability and back + leg pain only changed little during follow-up with no statistically significant differences between groups. At 1 year, back pain had on average decreased by 1.1 more on a 0-10 scale (95% confidence interval 0.20-1.97) in the group treated by lactic acid bacteria than in the control group. There were no differences regarding other predefined outcomes, i.e. global effect or percentage with minimal disability at 1 year. Nine per cent of the patients reported gastrointestinal side effects without difference between groups. CONCLUSIONS: No differences were found regarding the predefined outcomes. Overall, there was little improvement during the 1-year observation period. A small, though hardly clinically relevant, effect on back pain was seen after treatment by Lactobacillus Rhamnosis GG, and the treatment was without side effects in comparison with the control group.

Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling.

Background. Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion injury and may have beneficial effects in patients with stable cardiovascular disease. We investigated the effect of long-term RIC treatment in patients with chronic ischemic heart failure (CIHF). Methods. Prespecified post-hoc analysis of a prospective, exploratory and outcome-assessor blinded study. Twenty-one patients with compensated CIHF and 21 matched controls without heart failure or ischemic heart disease were treated with RIC once daily for 28 ± 4 days. RIC was conducted as 4 cycles of 5 minutes upper arm ischemia followed by 5 minutes of reperfusion. We evaluated circulating markers of inflammation and cardiac remodeling at baseline and following long-term RIC. Results. RIC reduced C-reactive protein from 1.5 (0.6-2.5) to 1.3 (0.6-2.1) mg/l following long-term RIC treatment (p = .02) and calprotectin from 477 (95% CI 380 to 600) to 434 (95% CI 354 to 533) ng/ml (p = .03) in patients with CIHF, but not in matched controls. Overall, RIC did not affect circulating markers related to adaptive or innate immunology or cardiac remodeling in patients with CIHF. Among patients with CIHF and N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels above the geometric mean of 372 ng/l, long-term RIC treatment reduced soluble ST2 (n = 9) from 22.0 ± 3.7 to 20.3 ± 3.9 ng/ml following long-term RIC treatment (p = .01). Conclusion. Our findings suggest that long-term RIC treatment has mild anti-inflammatory effects in patients with compensated CIHF and anti-remodeling effects in those with increased NT-proBNP levels. This should be further investigated in a randomized sham-controlled trial.

NSAID consumption and risk of acute myeloid leukemia: a national population-based case-control study.

BACKGROUND: Most cases of acute leukemia arise without identifiable risk factors. Studies investigating the impact of autoimmune diseases and infections on leukemogenesis have revealed conflicting results. If inflammation increases the risk of acute myeloid leukemia (AML), nonsteroidal anti-inflammatory drug (NSAID) use may decrease the risk of leukemia. METHODS: We conducted a case-control study of 3,053 patients with AML diagnosed between 2000 and 2013, who were registered in the Danish National Acute Leukemia Registry, and 30,530 population controls matched on sex and age. We identified prescriptions through the Danish National Health Service Prescription Database. We used conditional logistic regression analysis to compute ORs associating AML with NSAID use overall, in patients with inflammatory diseases, and for specific AML subtypes (de novo AML, AML related to previous hematological disease, ie, secondary AML [sAML], or therapy-related AML [tAML; exposed to previous cytotoxic therapy]). RESULTS: Overall, NSAID use was not associated with a lower risk of AML (OR 1.1, 95% CI=1.0-1.2), de novo AML (OR 1.0, 95% CI=0.9-1.1), and sAML/tAML (OR 1.3, 95% CI=1.1-1.5). In addition, in patients with known inflammatory diseases, NSAIDs did not affect AML risk (OR 0.9, 95% CI=0.5-1.6). Number of prescriptions, type of NSAID, age, or sex did not influence the results. CONCLUSION: In line with our recent findings that showed no association between autoimmune diseases and infections and de novo AML, NSAID use was not found to reduce the risk of AML.

[Diagnosing and treating rheumatoid arthritis].

Rheumatoid arthritis (RA) is a chronic, autoimmune joint disease associated with increased risk of multiorgan involvement and comorbidities such as osteoporosis, cardiovascular disease, and infections. Therefore, doctors in other specialities should have knowledge of RA. No diagnostic criteria are available, but the classification criteria are often used as a diagnostic tool. Early initiation of effective immunosuppressive treatment is essential to improve outcome. The cornerstone of treatment is intra-articular administration of glucocorticoids in combination with methotrexate.

Divergent effects on macrophage biomarkers soluble CD163 and CD206 in axial spondyloarthritis.

The chronic joint inflammation in axial spondyloarthritis (axSpA) is characterized by infiltration of activated macrophages. The haptoglobin-hemoglobin receptor CD163 and the mannose receptor CD206 are strongly expressed on M2c and M2a macrophages, respectively. We measured the soluble forms of the receptors (sCD163 and sCD206) in plasma (PL) in two axSpA cohorts. All patients fulfil the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA and/or the 1984 modified New York criteria for ankylosing spondylitis. The first cohort included anti-TNF-α treated patients with active axSpA (n = 30); the second cohort included patients in early disease stages (n = 38). Plasma sCD163 and sCD206 were both within the reference interval of healthy controls (HC), but sCD163 decreased slightly during anti-TNF-α treatment [baseline: 1.49 mg/L (IQR: 1.22-1.77 mg/L, 12 weeks: 1.29 (IQR: 1.09-1.57) mg/L, 20 weeks: 1.25 (IQR: 0.99-1.75) mg/L, 52 weeks: 1.39 (IQR: 1.15-1.78) mg/L], while sCD206 increased [baseline: 0.17 (IQR: 0.13-0.21) mg/L, 12 weeks: 0.19 (0.16-0.23) mg/L, 20 weeks: 0.20 (0.14-0.24) mg/L, 52: 0.19 (IQR: 0.14-0.23) mg/L], pointing toward a shift in polarization of involved macrophages. Plasma levels of sCD206 proved significantly higher in patients with early disease stages and definite radiological sacroiliitis (n = 10). This was not the case for sCD163. A significant increase in response to anti-TNF-α treatment, could suggest sCD206 as a marker of response to anti-TNF-α treatment, however, the potential for the two macrophage markers as diagnostic and prognostic indicators of disease in axSpA is weak.

Autoimmune diseases, infections, use of antibiotics and the risk of acute myeloid leukaemia: a national population-based case-control study.

Previous studies reported increased risk of acute myeloid leukaemia (AML) in individuals with inflammatory conditions. However, it is unclear whether this association is explained by preceding cytotoxic therapy or haematological diseases. We conducted a nationwide case-control study that included 3053 AML patients, diagnosed in Denmark between 2000 and 2013, and 30 530 sex- and age-matched population controls. We retrieved information on autoimmune disease, infections, and use of antibiotics and computed odds ratios for AML (conditional logistic regression). Results were stratified by AML type, sex, and age. Autoimmune diseases were associated with an overall increased risk of AML {odds ratio [OR] 1·3 [95% confidence interval (CI) = 1·1-1·5]}. However, the risk was confined to patients with previous haematological disease or cytotoxic therapy exposure [secondary/therapy-related AML (sAML/tAML0) OR 2·0 (95% CI = 1·6-2·6)] and not de novo AML [OR 1·1 (95% CI = 0·9-1·3)]. Similarly, any prior infection requiring hospitalization was associated with a higher risk of AML [OR 1·3 (95% CI = 1·1-1·4)]. Again, this association was evident for sAML/tAML [OR 1·8 (95% CI = 1·5-2·2)], and not de novo AML [OR 1·1 (95% CI = 1·0-1·2)]. In conclusion, autoimmune diseases and infections were associated with an increased AML risk only in subjects with prior haematological disease and/or cytotoxic treatment. These observations suggest, that inflammation plays - if any - a minor role for the development of de novo AML.

Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis.

Spondyloarthritis (SpA) is characterized by inflammation and new bone formation and can be treated by inhibition of the proinflammatory cytokines TNF-α and IL-17A. IL-26 is considered a proinflammatory cytokine, predominantly related to Th17 cells. In the present study, we investigate IL-26 expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were stained for IL-26 and analyzed by fluorescence microscopy. Synovial fluid mononuclear cells, C-C motif chemokine receptor 6 memory Th17 cells, and fibroblast-like synoviocytes (FLSs) were isolated, and supernatants were analyzed for IL-26 content by ELISA. FLSs were further stained for IL-26 production and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma (P < 0.0001). Moreover, IL-26 expression was found in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA+ myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts (P = 0.02). In conclusion, IL-26 seems to be produced by myofibroblasts in the inflamed synovium and could be a possible facilitator of bone mineralization in SpA. KEY MESSAGES: IL-26 levels are higher in synovial fluid compared to plasma in spondyloarthritis. IL-26 was identified in axial facet joints of spondyloarthritis patients. Myofibroblasts from the spondyloarthritis synovium produce large amounts of IL-26. IL-26 induces bone mineralization in human osteoblasts.

Association between tobacco smoking and response to tumour necrosis factor α inhibitor treatment in psoriatic arthritis: results from the DANBIO registry.

OBJECTIVES: To investigate the association between tobacco smoking and disease activity, treatment adherence and treatment responses among patients with psoriatic arthritis (PsA) initiating the first tumour necrosis factor α inhibitor therapy (TNFi) in routine care. METHODS: Observational cohort study based on the Danish nationwide DANBIO registry. Kaplan-Meier plots, logistic and Cox regression analyses by smoking status (current/previous/never smoker) were calculated for treatment adherence, ACR20/50/70-responses and EULAR-good-response. Additional stratified analyses were performed according to gender and TNFi-subtype (adalimumab/etanercept/infliximab). RESULTS: Among 1388 PsA patients included in the study, 1148 (83%) had known smoking status (33% current, 41% never and 26% previous smokers). Median follow-up time was 1.22 years (IQR 0.44-2.96). At baseline, current smokers had lower Body Mass Index (27 kg/m(2) (23-30)/28 kg/m(2) (24-31)) (median (IQR)), shorter disease duration (3 years (1-8)/5 years (2-10)), lower swollen joint count (2 (0-5)/3 (1-6)), higher visual-analogue-scale (VAS) patient global (72 mm (54-87)/68 mm (50-80)), VAS fatigue (72 mm (51-86)/63 mm (40-77)) and Health Assessment Questionnaire (HAQ) score (1.1 (0.7 to 1.5)/1.0 (0.5 to 1.5)) than never smokers (all p<0.05). Current smokers had shorter treatment adherence than never smokers (1.56 years (0.97 to 2.15)/2.43 years (1.88 to 2.97), (median (95% CI)), log rank p=0.02) and poorer 6 months' EULAR-good-response rates (23%/34%), ACR20 (24%/33%) and ACR50 response rates (17%/24%) (all p<0.05), most pronounced in men. In current smokers, the treatment adherence was poorer for infliximab (HR) 1.62, 95% CI 1.06 to 2.48) and etanercept (HR 1.74, 1.14 to 2.66) compared to never smokers, but not for adalimumab (HR 0.80, 0.52 to 1.23). CONCLUSION: In PsA, smokers had worse baseline patient-reported outcomes, shorter treatment adherence and poorer response to TNFi's compared to non-smokers. This was most pronounced in men and in patients treated with infliximab or etanercept.

Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis.

INTRODUCTION: Spondyloarthritis (SpA) comprises a group of diseases often associated with HLA-B27 and characterized by inflammation of the entheses and joints of the axial skeleton. The inflammatory process in SpA is presumably driven by innate immune cells but is still poorly understood. Thus, new tools for monitoring and treating inflammation are needed. The family of CD18 integrins is pivotal in guiding leukocytes to sites of inflammation, and CD18 hypomorphic mice develop a disease resembling SpA. Previously, we demonstrated that altered soluble CD18 (sCD18) complexes in the blood and synovial fluid of patients with arthritis have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity. METHODS: Plasma levels of sCD18 in a study population with 84 patients with SpA and matched healthy controls were analyzed with a time-resolved immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synoviocytes (FLSs) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMCs) was studied with flow cytometry and TRIFMA. RESULTS: Plasma levels of sCD18 were decreased in patients with SpA compared with healthy volunteers (P <0.001), and the lowest levels were in the HLA-B27-positive subgroup (P <0.05). In a multiple regression model, the sCD18 levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P <0.05), the level of morning stiffness (P <0.05), the Bath Ankylosing Spondilitis Metrology Index (P <0.05), the physician global assessment score (P <0.01), and the sacroiliac magnetic resonance imaging activity score (P <0.05). The mechanisms for these changes could be simulated in vitro. First, sCD18 in plasma adhered to inflammation-induced intercellular adhesion molecule 1 (ICAM-1) on endothelial cells and FLS, indicating increased consumption. Second, CD18 shedding from SpA PBMCs correlated inversely with the BASDAI (P <0.05), suggesting insufficient generation. CD18 was shed primarily from intermediate CD14⁺⁺ CD16⁺ monocytes, supporting the view that alterations in innate immunity can regulate the inflammatory processes in SpA. CONCLUSIONS: Taken together, the failure of patients with SpA to maintain adequate sCD18 levels may reflect insufficient CD18 shedding from monocytes to counterbalance the capture of sCD18 complexes to inflammation-induced ICAM-1. This could increase the availability of ICAM-1 molecules on the endothelium and in the synovium, facilitating leukocyte migration to the entheses and joints and aggregating disease activity.