Macrophage re-programming by JAK inhibitors relies on MAFB.

Monocyte-derived macrophages play a key pathogenic role in inflammatory diseases. In the case of rheumatoid arthritis (RA), the presence of specific synovial tissue-infiltrating macrophage subsets is associated with either active disease or inflammation resolution. JAK inhibitors (JAKi) are the first targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) approved for treatment of RA with comparable efficacy to biologics. However, the effects of JAKi on macrophage specification and differentiation are currently unknown. We have analyzed the transcriptional and functional effects of JAKi on human peripheral blood monocyte subsets from RA patients and on the differentiation of monocyte-derived macrophages promoted by granulocyte-macrophage colony-stimulating factor (GM-CSF), a factor that drives the development and pathogenesis of RA. We now report that JAKi Upadacitinib restores the balance of peripheral blood monocyte subsets in RA patients and skewed macrophages towards the acquisition of an anti-inflammatory transcriptional and functional profile in a dose-dependent manner. Upadacitinib-treated macrophages showed a strong positive enrichment of the genes that define synovial macrophages associated to homeostasis/inflammation resolution. Specifically, Upadacitinib-treated macrophages exhibited significantly elevated expression of MAFB and MAFB-regulated genes, elevated inhibitory phosphorylation of GSK3ß, and higher phagocytic activity and showed an anti-inflammatory cytokine profile upon activation by pathogenic stimuli. These outcomes were also shared by macrophages exposed to other JAKi (baricitinib, tofacitinib), but not in the presence of the TYK2 inhibitor deucravacitinib. As a whole, our results indicate that JAKi promote macrophage re-programming towards the acquisition of a more anti-inflammatory/pro-resolution profile, an effect that correlates with the ability of JAKi to enhance MAFB expression.

Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry.

OBJECTIVES: To compare the safety of Janus kinase inhibitors (JAKi) with that of tumour necrosis factor inhibitors (TNFi) and determine drug persistence among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We analysed data from patients included in BIOBADASER 3.0 and treated with JAKi or TNFi from 2015 to 2023 and estimated the incidence rate ratio (IRR) of adverse events and persistence. RESULTS: A total of 6826 patients were included. Of these, 52% had RA, 25% psoriatic arthritis and 23% axial SpA. Treatment was with TNFi in 86%. The mean duration of treatment was 2.2±2.0 years with TNFi versus 1.8±1.5 with JAKi. JAKis were prescribed in older patients with longer term disease, greater comorbidity and later treatment lines and more frequently as monotherapy. The IRR of all infections and gastrointestinal events was higher among patients with RA treated with JAKi. Drug persistence at 1, 2 and 3 years was 69%, 55% and 45% for TNFi and 68%, 54% and 45% for JAKi. Multivariate regression models showed a lower probability of discontinuation for JAKi (HR=0.85; 95% CI 0.78-0.92) and concomitant conventional synthetic disease-modifying antirheumatic drugs (HR=0.90; 95% CI 0.84-0.96). The risk of discontinuation increased with glucocorticoids, comorbidities, greater disease activity and later treatment lines. CONCLUSIONS: Infections, herpes zoster and gastrointestinal adverse events in patients with RA tended to be more frequent with JAKi. However, prognosis was poor in patients receiving JAKi. Persistence was similar for TNFi and JAKi, although factors associated with discontinuation differed by diagnostic group.

Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis.

OBJECTIVE: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. METHODS: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. RESULTS: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). CONCLUSIONS: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.

Long-Term Survival of Subcutaneous Biosimilar Tumor Necrosis Factor Inhibitors Compared to Originators: Results From a Multicenter Prospective Registry.

OBJECTIVE: To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. METHODS: Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. RESULTS: A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. CONCLUSION: No significant differences were found between treatments in long-term survival due to inefficacy or AEs.

Opioids and fibromyalgia: frequency of use and factors associated with increased consumption in patients remitted to a tertiary care center.

BACKGROUND: Opioids are not recommended for fibromyalgia. OBJECTIVE: To investigate the frequency of opioid use in a large cohort of fibromyalgia patients and to identify factors associated with opioid consumption. METHODS: A retrospective, observational study of a large fibromyalgia cohort in a tertiary care center. We assessed fibromyalgia severity, functional capacity, anxiety, depression, drugs consumption and the patient's impression of change. We compared strong opioid consumers (SOC) and non-SOC. Inferential statistical and logistic regression analysis were used to identify factors associated with opioid consumption, and ANOVA for repeated measurements. RESULTS: We found a prevalence of 9.2% of SOC (100 patients) among 1087 patients in the cohort. During the last four years there was a significant increase on the incidence of SOC up to 12.8% (p = 0.004). There were no differences in demographic variables between SOC and non-SOC. Clinical variables were significantly more severe in SOC, and they consumed more non-opioid drugs (p < 0.0001). Opioid consumption was independently associated with other non-opioid drugs (Odds ratio 1.25, CI: 1.13-1.38), but not with the fibromyalgia severity. At three months, 62% of the patients had opioid withdrawal. There were no statistical differences in the fibromyalgia severity at the initial evaluation, or the patient's impression of change compared with those patients who continued opioids. Coping strategies were better in those patients who withdrew opioids (p = 0.044). CONCLUSIONS: We observed an increase in opioid prescriptions during the last four years. Opioid consumption was associated with concomitant use of non-opioid drugs, but it was not associated with fibromyalgia severity.

Second and third TNF inhibitors in European patients with axial spondyloarthritis: Effectiveness and impact of the reason for switching.

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with 1) treatment line (second and third TNFi-series) and 2) reason for withdrawal from the preceding TNFi (lack of efficacy (LOE) versus adverse events (AE)). METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission (Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)) were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE versus LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE < 26 versus ≥26 weeks) (58% versus 71%, p< 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) versus LOE (17%), p< 0.001, while similar for the third TNFi (19% versus 13%, p= 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE versus LOE.

Oral or pulse glucocorticoid use at the onset of giant cell arteritis and its influence on the risk of relapse: a retrospective study.

The objective is to investigate whether initial therapy with intravenous methylprednisolone pulses (ivMTP) or oral glucocorticoid (OG) influences the relapse rate in giant cell arteritis (GCA) patients. This is a retrospective observational study of patients with GCA from 2004 to 2021. Demographics, clinical and laboratory variables, cumulative glucocorticoid dose and relapse rate at 6-month follow-up defined according to EULAR recommendations were recorded. Univariate and multivariate logistic regression models were used to determine possible risk factors for relapse. A total of 74 GCA patients were included for analysis (54 (73%) female, mean (SD) age 77.2 (7.4) years). Overall, 47 (63.5%) patients received ivMTP at disease onset and 27 (36.5%) OG. Mean (SD) cumulative prednisone dose (mg) at 6-month follow-up was 3790.7 (1832.7) for patients with ivMTP vs 4298.1 (2930.6) for the OG group, p = 0.37. A total of 15 (20.3%) relapses occurred at 6-month follow-up. Relapse rates did not differ according to the initial therapy (19.1 vs 22.2%, respectively, p = 0.75). In the multivariate analysis, fever at disease onset (OR 4.837; CI 1.1-21.6) and dyslipidemia (OR 5.651; CI 1.1-28.4) were independent predictors for relapse. Initial therapy with ivMTP or OG does not influence the relapse rate of GCA patients. Fever at disease onset and dyslipidemia are independent predictors of disease relapse.

The role of ultrasound and FDG-PET/CT to detect extracranial artery involvement in patients with suspected large vessel vasculitis.

OBJECTIVE: To assess the accuracy of ultrasound (US) versus fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) to identify extracranial involvement in large vessel vasculitis (LVV). METHODS: A retrospective observational study of patients with suspected LVV. All patients underwent US exam within 24 h per protocol. FDG-PET/CT was performed according to clinician criteria. The gold standard for LVV diagnosis was clinical confirmation after 6 months. RESULTS: Of the 113 patients included (74.3% female, mean age 74 years), 37 (32.7%) were diagnosed with LVV after 6 months. The sensitivity and specificity of US were 86.5% and 96.1%, respectively. Only 12 (42.9%) of 28 patients undergoing a FDG-PET/CT per clinician criteria showed positive findings. The sensitivity and specificity of FDG-PET/CT for LVV were 61.1% and 90%, respectively. Taking FDG-PET/CT as the reference, US showed extracranial inflammation in 10/12 (83.3%) and detected 2 (12.5%) additional cases of extracranial involvement with negative FDG-PET/CT. Conversely, FDG-PET/CT was positive in two patients with negative US (one isolated aortitis and one aortoiliac involvement). CONCLUSIONS: US and FDG-PET/CT are both valid tools to detect extracranial involvement. The presence of US extracranial artery inflammation is consistent with FDG-PET/CT examination, although a negative US scan does not rule out extracranial involvement.

Prevalence of post-COVID-19 in patients with fibromyalgia: a comparative study with other inflammatory and autoimmune rheumatic diseases.

OBJECTIVES: To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients. METHODS: Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group. RESULTS: RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p <  0.0001). Only loss of smell was more frequent in the FM group (p = 0.005). The FM group with PC (n = 29) showed more severity of the Combined Index of Severity in Fibromyalgia (ICAF) total score and physical factor after COVID-19, while emotional, coping factors and the ACR criteria did not change. CONCLUSIONS: The prevalence of PC in FM patients is similar to RD patients. In FM patients, the presence of PC does not appear to impact the severity of FM.

Clinical impact of confinement due to the COVID-19 pandemic on patients with fibromyalgia: a cohort study.

OBJECTIVES: To our knowledge, the impact of the COVID-19 pandemic on fibromyalgia (FM) patients has not been studied before. FM patients often experience clinical impairment with stress. The aim of this study was to determine whether severity of FM increases because of confinement by the COVID-19 pandemic. METHODS: This prospective study includes patients from the Combined Index of Severity of Fibromyalgia (ICAF) cohort who met the 2010 ACR FM criteria. In this cohort, all patients have a periodical evaluation of their quality of life through two questionnaires, the ICAF, which assesses the ability to perform daily living activities, anxiety and depression, and through the Patient Global Impression of Change (PGIC), which assesses overall change after a therapeutical intervention. Pre- and post-confinement measurements were analysed. Inferential statistical analysis and ANOVA for repeated measurements were used. RESULTS: A total of 93 patients received a phone consultation, (95.5% females), mean (SD) age of 48.23 (8.38) years. Four patients were excluded as presenting COVID-19 and 51 (57%) completed the post-confinement ICAF. Following confinement, 25 (49%) patients got worse (group-worse) and 26 (51%) patients experienced no change or improved (group-stable). Comparisons between pre- and post-confinement ICAF did not show significant differences in both groups. Passive coping was significantly different in group-worse in pre-confinement evaluation. In the 80% of patients with passive coping predominance there were no changes in coping strategy. CONCLUSIONS: No clinical impairment due to COVID-19 confinement occurred. The perceived worsening among FM patients relies primarily on how patients cope with their disease, without a real impact on clinical manifestations.

Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study.

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.

Prevalence of hospital PCR-confirmed COVID-19 cases in patients with chronic inflammatory and autoimmune rheumatic diseases.

BACKGROUND: The susceptibility of patients with rheumatic diseases and the risks or benefits of immunosuppressive therapies for COVID-19 are unknown. METHODS: We performed a retrospective study with patients under follow-up in rheumatology departments from seven hospitals in Spain. We matched updated databases of rheumatology patients with severe acute respiratory syndrome coronavirus 2-positive PCR tests performed in the hospital to the same reference populations. Rates of PCR+ confirmed COVID-19 were compared among groups. RESULTS: Patients with chronic inflammatory diseases had 1.32-fold higher prevalence of hospital PCR+ COVID-19 than the reference population (0.76% vs 0.58%). Patients with systemic autoimmune or immune-mediated disease (AI/IMID) showed a significant increase, whereas patients with inflammatory arthritis (IA) or systemic lupus erythematosus did not. COVID-19 cases in some but not all diagnostic groups had older ages than cases in the reference population. Patients with IA on targeted-synthetic or biological disease-modifying antirheumatic drugs (DMARDs), but not those on conventional-synthetic DMARDs, had a greater prevalence despite a similar age distribution. CONCLUSION: Patients with AI/IMID show a variable risk of hospital-diagnosed COVID-19. Interplay of ageing, therapies and disease-specific factors seem to contribute. These data provide a basis to improve preventive recommendations to rheumatic patients and to analyse the specific factors involved in COVID-19 susceptibility.

Coronavirus disease 2019 (COVID-19) in autoimmune and inflammatory conditions: clinical characteristics of poor outcomes.

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Health Disparities Among Hispanics With Rheumatoid Arthritis: Delay in Presentation to Rheumatologists Contributes to Later Diagnosis and Treatment.

OBJECTIVE: The aim of this study was to evaluate referral and treatment delays by ethnicity/race in patients with rheumatoid arthritis (RA) treated at an academic rheumatology center. METHODS: We reviewed the medical records of all RA patients evaluated at an outpatient clinic between 2011 and 2016 to identify newly diagnosed and naive-to-treatment patients. We determined the durations between symptom onset and first rheumatology visit and time to initiate treatment. Data extraction included referral source, demographics, treatment, and laboratory tests. Routine use of a multidimensional health assessment questionnaire allowed us to calculate baseline RAPID3 (routine assessment of patient index data 3) scores. Comparisons between self-reported ethnicity/race groups were performed. We used logistic regression models to analyze associations between baseline variables and early referral. RESULTS: Data from 152 disease-modifying antirheumatic drug-naive RA patients were included in the study; 35% were white, 37% black, 20% Hispanic, and 8% other. The range in median time to first rheumatology visit was 6 to 8 months for all patient groups, except Hispanic. This group had a median time of 22.7 months (p = 0.01). The referral pattern was considerably variable between-groups; 40% of Hispanic patients were self-referred (p = 0.01). There were no statistically significant between-group differences for time to treatment initiation according to ethnicity/race. RAPID3 scores (p = 0.04) and erythrocyte sedimentation rates (p = 0.01) were significantly higher in the black and Hispanic groups. A high C-reactive protein value at baseline was associated with earlier referral. CONCLUSIONS: There is significant delay in initial presentation to a rheumatologist that was associated with a higher disease severity at presentation, especially for Hispanic patients.

Low socioeconomic status and patient questionnaires in osteoarthritis: challenges to a "biomedical model" and value of a complementary "biopsychosocial model".

Modern medical care is based largely on a paradigm known as a "biomedical model," in which "objective," high-technology biomarkers guide clinical care, and most health outcomes are determined by health professionals rather than individuals, using drugs as the primary therapy. The biomedical model is spectacularly effective in the acute care inpatient hospital, the setting for 95% of medical education and training, and to guide management of many chronic diseases, such as hypertension and diabetes, for which a "gold standard" biomarker is a major determinant of clinical decisions. This model also has contributed importantly to knowledge of biomarkers, biochemical and structural abnormalities in osteoarthritis (OA) and other rheumatic diseases. However, a biomedical model has many limitations in understanding the long-term course of OA and many chronic diseases in outpatient medicine, the setting of 95% of activities that determine long-term health outcomes. Patient self-report questionnaires provide the most informative data concerning OA patient status and changes in status, and more significant data in the prognosis of outcomes such as mortality than laboratory or radiographic measures. Furthermore, the incidence, prevalence, morbidity, and mortality of OA is considerably greater in individuals of low versus high socioeconomic status. These associations are not unique to OA, and are seen in many diseases, including comorbid conditions which are the acute causes of death in OA. Associations of low socioeconomic and poor health are explained only in small part by limited access to medical services, the conventional explanation. Strong evidence suggests that socioeconomic status is a surrogate marker for patient self-management, actions and environment, in addition to actions of health professionals, in the pathogenesis, course and outcomes of chronic diseases. These observations suggest the value of a complementary "biopsychosocial model" to better understand pathogenesis, principles of treatments, and outcomes in OA and other chronic diseases. Inclusion of clinical information from patient questionnaires and socioeconomic status variables in clinical and research settings could add new understanding of biomarkers and pain in OA for both basic and clinical investigators. Furthermore, the data indicate that poor physical function assessed on a self-report questionnaire might be regarded as an important reversible risk factor in public health and research agendas, for which the OA community might be strong advocates.

Patient questionnaires in osteoarthritis: what patients teach doctors about their osteoarthritis on a multidimensional health assessment questionnaire (MDHAQ) in clinical trials and clinical care.

A patient history generally provides the most important information in diagnosis and management of patients with most rheumatic diseases, including osteoarthritis (OA). Patient history components can be expressed as quantitative, structured, "scientific" data, rather than "subjective" narrative descriptions, using patient self-report questionnaires. The Western Ontario McMaster (WOMAC) questionnaire is used in all OA clinical trials, and the health assessment questionnaire (HAQ) in all rheumatoid arthritis (RA) clinical trials, as "disease-specific" questionnaires. However, both questionnaires include scores for physical function function and pain; physical function scores are correlated highly significantly at r=0.78 in both RA and OA patients, while WOMAC pain scores are correlated with HAQ visual analogue scale (VAS) pain scores at r=0.73 in OA and r=0.71 in RA. Therefore, the WOMAC and HAQ may be regarded as largely "generic" questionnaires, at least for people with arthritis. Since it is not feasible to ask patients with different diagnoses to complete different care questionnaires in busy clinical settings, a single multidimensional HAQ (MDHAQ), derived from the HAQ and largely similar and informative in all rheumatic diseases, has been used in all rheumatology patients in several settings. The MDHAQ also has been incorporated into two OA clinical trials, with virtually identical results to the WOMAC. In routine clinical care, MDHAQ scores have documented that the disease burden of OA is comparable to RA in terms of scores for pain, physical function, and RAPID3 (routine assessment of patient index data) an index of pain, function and patient global assessment. Further observations indicate capacity of the MDHAQ to recognise fibromyalgia similarly to formal fibromyalgia criteria, as well as the ineffectiveness of opioids in OA, and similar prevalence of depression and other psychological issues in OA to RA. These findings also illustrate the value of a database of MDHAQ data for retrospective analysis of serendipitous observations from routine clinical care.

Anterior uveitis in patients with spondyloarthropathies in a single US academic center: a retrospective study.

Uveitis may represent an opportunity to diagnose spondyloarthropathies (SpA) earlier and influence treatment decisions. We describe the percentage of acute anterior uveitis (AAU) in a diverse group of SpA patients seen at one academic setting and compare demographic and clinical characteristics according to the presence of uveitis. We conducted a retrospective study of patients with SpA and AAU (January 2016-June 2017). Patients were identified using ICD-10 and administrative claim codes, diagnoses were confirmed through chart review. Extracted data included demographics, laboratory, clinical data, treatment and Routine Assessment of Patient Index Data 3 (RAPID3) scores based on Multidimensional Health Assessment Questionnaire (MDHAQ). Baseline description and comparison between the two groups were performed. We included 190 patients, mostly men (59.5%), with a mean age of 45.9 years: 48% with ankylosing spondylitis (AS), 26% with psoriatic arthritis (PsA), 22% with undifferentiated SpA, and 4% with SpA associated with inflammatory bowel disease (IBD). Uveitis was identified in 17% of patients, ranging from 25% in AS to 4% in PsA. Time from symptom onset to SpA diagnosis was longer in patients with uveitis (10.9 versus 5.9 years, p < 0.001). A higher percentage of patients with uveitis were HLA-B27 positive (85% versus 67%, p = 0.02). The prevalence of uveitis in our population was 17%, slightly lower than previously reported in the literature. There was a diagnostic delay of about 7 years, significantly longer in patients with uveitis. New screening strategies in collaboration with ophthalmology may lead to earlier diagnosis and better outcomes.

Discordance of global assessment by patients and physicians is higher in osteoarthritis than in rheumatoid arthritis: a cross-sectional study from routine care.

The study compares patient-physician discordance in global assessment in patients with osteoarthritis (OA) versus patients with rheumatoid arthritis (RA) seen in routine care. This is a cross-sectional study conducted at an academic rheumatology center at which all patients are asked to complete a Multi-Dimensional Health Assessment Questionnaire (MDHAQ), which includes a patient global assessment (PATGL). Rheumatologists are encouraged to complete a physician questionnaire, which includes a physician global assessment (DOCGL). Patients with either OA or RA were identified using ICD9 codes and classified as positive discordance (PATGL-DOCGL ≥ 2), negative discordance (PATGL-DOCGL≤ - 2), and concordance (absolute difference between the two assessments < 2). Discordance was assessed by diagnosis. Agreement between patient and physician global assessments was evaluated using intraclass correlations. Logistic regression was performed to identify explanatory variables for positive discordance. The analysis included 243 OA and 216 RA patients. Mean PATGL was higher in OA versus RA (5.4 versus 4.2, p = 0.005), while mean DOCGL was similar (4.0 versus 3.8, p = 0.23) leading to a higher patient-physician discordance in OA (1.35 versus 0.43, p < 0.001). Positive discordance occurred in 34% of OA versus 18% of RA patients (p < 0.001). Intraclass correlation coefficients were 0.43 in OA versus 0.60 in RA patients. In logistic regressions, pain was the only statistically significant explanatory variable for discordance in both OA (OR 1.34, 95% CI 1.12-1.78) and RA (OR 1.47 95% CI 1.04-2.07). Patients with OA are more likely to be discordant with their rheumatologists than patients with RA because of a higher PATGL. Similarly to RA, the most important explanatory variable for discordance was higher pain.

Assessment of pain and other patient symptoms in routine clinical care as quantitative, standardised, "scientific" data.

Pain is the most common basis for visits to a rheumatologist, and reduction of pain is a primary goal of clinical care. Pain is assessed optimally by the patient on a self-report questionnaire. In clinical trials and other clinical research concerning pain and pain relief, detailed questionnaires are generally completed by patients. However, in routine clinical care, pain is generally assessed only according to narrative descriptions by the physician, and only a minority of settings assess pain using a standard, quantitative measure. Accurate, standard, quantitative assessment of pain in routine care is easily assessed in all patients with all diagnoses on a 0-10 visual analogue scale (VAS), by asking each patient to complete a 2-page multidimensional health assessment questionnaire/routine assessment of patient index data 3 (MDHAQ/RAPID3) at all visits. The MDHAQ includes VAS for pain, patient global assessment, and fatigue, as well as a quantitative physical function scale, RAPID3, review of systems, and recent medical history. The questionnaire provides the doctor with a 10-15 second overview of medical history data that otherwise would require about 10-15 minutes of conversation, saving time for the doctor and patient to focus on the most prominent concerns for the visit. MDHAQ scores from patients with 10 different rheumatic diagnoses, and specific data indicating similarity of scores in patients with osteoarthritis versus rheumatoid arthritis on the same questionnaire, are presented to illustrate the value of the MDHAQ in routine care.