Disease Activity Outcomes Research Articles

Associations between physicians' global assessment of disease activity and patient-reported outcomes in patients with systemic lupus erythematosus: A longitudinal study.

To determine longitudinal associations between Physician Global Assessment (PGA) and patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE). Patients attending a rheumatology clinic between 2013 and 2017 completed specific (SLEQOL) and generic (SF36) health-related quality of life (HRQoL) surveys and rated their global rating of change (GRC) at each visit. PGA, SLEDAI-2K and SLE Flare Index (SFI) were also captured on all visits. Generalised estimating equations (GEE) methods were used to examine longitudinal associations of PGA with PROs and clinical indicators. 337 patients were followed for a median [IQR] of 3.2 [1.6, 3.4] years (2,059 visits). High PGA (>1) was strongly associated with high SLEDAI-2K scores, the presence of flares and poor PROs. Odd ratios (OR) [95% CI] of PGA > 1 in patients with SLEDAI-2K >4 & <10 and SLEDAI-2K ≥10, compared to SLEDAI-2K ≤ 4, were 3.46 [2.36, 5.08], p < 0.001 and 6.39 [4.30, 9.49], p < 0.001, respectively. OR [95% CI] of PGA > 1 in patients with mild-to-moderate or severe flares were 2.09 [1.62, 2.71], p < 0.001 and 4.42 [3.21, 6.07], p < 0.001, respectively. Mental components of both SLEQOL (mood, self-image) and SF36 (MCS) surveys demonstrated significant associations with high PGA. After adjusting for SLEDAI-2K, one-point increase in PGA was associated with reductions in SLEQOL total score and SF36-MCS by 2.33 (regression coefficient (RC) [95% CI] = -2.33 [-3.77, -0.88], p = 0.002), and 4.16 (RC [95% CI] = -4.16 [-5.19, -3.13], p < 0.001) points, respectively. Associations of some physical components (SLEQOL-symptoms, and SF36-PCS) with PGA attenuated when adjusted for SLEDAI-2K. Patients who rated low scores of GRC, which indicate health deterioration, were twice as likely to have PGA > 1 (OR [95%CI] 1.99 [1.25, 3.16], p = 0.004). High PGA was strongly associated with poor mental health, high disease activity and flares. This study confirms the value of PGA as an efficient assessment tool for SLE.

Crohn\u2019s disease and ulcerative colitis patient-reported outcomes signs and symptoms for the remote management of inflammatory bowel disease during the COVID-19 pandemic

Background and aimsThe COVID-19 pandemic has led to a deep reorganization of hospital services including inflammatory bowel disease (IBD) units. In this situation, conversion of in-person routine follow-up visits into phone consultations might be necessary. Here we explored the feasibility of using the validated Crohn’s Disease (CD) or Ulcerative Colitis (UC) Patient-Reported Outcomes Signs and Symptoms (CD- and UC-PRO/SS) to collect data about abdominal symptoms (abdominal/S) and bowel signs and symptoms (bowel/SS) remotely.MethodsCD- and UC-PRO/SS were collected during phone consultations and compared among patients with active and inactive disease. The effectiveness of therapeutic intervention in patients with active disease was assessed by PRO/SS variation.ResultsTwenty-one CD and 56 UC patients were evaluated by phone. Six (28.6%) CD and 15 (26.8%) UC patients were considered to have active disease. In CD the bowel/SS but not the abdominal/S module was significantly higher in active patients (mean bowel/SS 2.50 [SE ± 0.44] active vs 0.76 [SE ± 0.18] remission, p = 0.008, AUC 0.87; mean abdominal/S 1.11 [SE ± 0.38] active vs 0.24 [SE ± 0.13] remission, p = 0.066). UC-PRO/SS measures were significantly higher in active patients as compared to patients in remission (median bowel/SS 1.63 [SE ± 0.24] active vs 0.33 [SE ± 0.04] remission; p < 0.0001, AUC 0.91; mean abdominal/S 1.03 [SE ± 0.24] vs 0.37 [SE ± 0.12]; p = 0.009, AUC 0.71). Therapy was escalated in 12 patients (3 CD and 9 UC) due to disease relapse. Therapy escalation resulted in the reduction of PRO/SS as evaluated at the subsequent phone consultation.ConclusionsPRO/SS might represent a feasible tool to evaluate disease activity and therapy outcome in IBD patients during periods of limited access to outpatient clinics.

Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA. In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life. Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient β=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient β=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient β= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors. Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.

IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients.

ObjectiveRheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients.Materials and MethodsIn total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays.ResultsIn the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS.ConclusionsThe obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.

Clinical Characteristics of Adult Patients with Systemic Vasculitis: Data of 1348 Patients from a Single Center.

To investigate the clinical characteristics of patients with systemic vasculitis in China by analyzing the data from a nationwide registry database, the Chinese Registry for Systemic Vasculitis (CRSV). The demographic data, clinical presentations, image and laboratory test results, disease activity assessment, treatment, and outcome of patients enrolled with the confirmed diagnosis of systemic vasculitis, including Takayasu's arteritis (TAK), ANCA-associated vasculitis (AAV), Behcet's syndrome (BD), Polyangitis nodosa (PAN), and unclassified systemic vasculitis (USV), were collected since July 2013 in the CRSV. The data during July 2013 and February 28 of 2020 were retrieved and analyzed. Up to February 2020, 3852 patients in total were registered in the CRSV. In Peking Union Medical College Hospital (PUMCH), 1348 patients were registered, including 730 patients with TAK, 343 with Behcet's disease (BD), 191 with AAV, 53 with USV, and 31 with PAN. More male patients were found in PAN (64.5%), BD (59.8%), and AAV (52.4%), while TAK was more prevalent in female patients (85.9%). The average age at disease diagnosis was 29.6 in TAK, 33.2 in BD, 28.6 in PAN, 39.4 in USV, and 48.1 in AAV. A significant difference was found between age at diagnosis of TAK and AAV. Gender comparisons revealed that the age at diagnosis of male patients with AAV was older than female patients. Hypertension (57.3%) and stroke (17.5%) were found to be more common in male patients with TAK, vascular involvement (27.3%) was found to be more common in male patients with BD, while neurological involvement (29.0%) was found to be more common in male patients with AAV than in females. This registry is the first in China and provides rich information about the clinical characteristics of Chinese patients with systemic vasculitis. There are significant differences in clinical presentations between different categories of systemic vasculitis.

DOP90 Physician global assessment of IBD Activity is associated with COVID-19 severity in patients aged less than 50 years

BackgroundSECURE-IBD is an international database that monitors COVID-19 outcomes in IBD patients. We examined the influence of IBD activity (reflected by Physician Global Assessment (PGA)) on COVID-19 severity, while exploring the modifying effect of age.MethodsWe analyzed 3,028 cases reported to SECURE-IBD from March 13-November 17, 2020. PGA was categorized as remission/mild (reference) vs moderate vs severe. Outcomes used as surrogates of severe SARS-CoV2 infection were hospitalization and a composite of ICU/ventilation/death. Using generalized estimating equations (GEE) to account for clustering by country, we determined the unadjusted association between disease activity and COVID-19 outcomes, overall and by age decade. We included the following covariates in multivariable GEE models a priori: time of COVID-19 diagnosis, age, sex, comorbidities (0, 1, ≥2), IBD type, systemic corticosteroids (CS), anti-TNF monotherapy, anti-TNF plus immune modulator, immune modulator monotherapy, and mesalamine. We included additional covariates (country GDP, race, BMI, anti-integrins and ustekinumab) if they changed the estimate by ≥10%. We also built models stratified by age; the age cut-off for stratification was determined using Joinpoint regression (selecting the age at which outcome rates significantly changed).ResultsCOVID-19 was more severe in patients with more active IBD: hospitalization rates 19% (remission/mild), 26% (moderate) and 45% (severe); ICU/ventilation/death rates 5% (remission/mild), 6% (moderate) and 12% (severe) (p<0.05, Figure 1). In unadjusted analyses, higher PGA was associated with an increased risk of hospitalization (moderate: OR 1.53, 95% CI 1.24–1.88; severe: OR 3.30, 95% CI 2.44–4.46) and ICU/ventilation/death (moderate: OR 1.44, 95% CI 1.10–1.87; severe: OR 2.58, 95% CI 1.71–3.90). As per Figure 2, the magnitude of association between severe PGA (vs remission/mild) and adverse outcomes was greatest in patients ≤50 years. Joinpoint regression also supported a significant change in the rate of ICU/ventilation/death at 50 years. In multivariable analyses (Figure 3), PGA remained significantly associated with hospitalization, but not ICU/ventilation/death. However, in multivariable analyses stratified by age, PGA was consistently associated with both hospitalization and ICU/ventilation/death in patients ≤50, but not >50 years. ConclusionOur data suggest an association between IBD activity, as assessed by PGA, and severe COVID-19 outcome with an increased risk in younger patients. Adequate IBD treatment despite the pandemic is needed to avert poor outcome to symptomatic SARS-CoV2 infections.

POS0656 RELATIONSHIP BETWEEN CHANGES IN LIPID LEVELS AND IMPROVEMENT IN DISEASE ACTIVITY OUTCOMES IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB TREATMENT: POOLED ANALYSIS OF DATA FROM TWO PHASE 3 STUDIES

Background:Upadacitinib (UPA) is an oral Janus kinase (JAK) inhibitor engineered to have greater selectivity for JAK1 vs JAK2, JAK3, and tyrosine kinase 2, and is approved for the treatment of RA. Across 2 double-blind, placebo (PBO)-controlled Phase 3 studies of UPA in patients with RA, after an initial increase through Week 8, lipid levels remained stable up to Week 24.1,2 Previous studies of JAK or IL-6 receptor inhibitors have reported a negative correlation between changes in lipid levels and RA disease activity.3,4Objectives:To determine the relationship between changes in lipid levels and disease activity outcomes in patients with RA treated with UPA.Methods:Patients with RA and an inadequate response to conventional synthetic/biologic DMARDs (cs/bDMARD-IR) from SELECT-NEXT/SELECT-BEYOND, respectively, were randomized to receive UPA 15 mg once daily (QD), UPA 30 mg QD, or PBO for 12 weeks followed by an extension of up to 5 years; patients randomized to PBO switched to UPA 15 or 30 mg after 12 weeks. Spearman correlations of maximum changes from baseline (BL) through Week 12 in fasting-state lipid levels (low- and high-density lipoprotein cholesterol [LDL-C; HDL-C], and total cholesterol [TC]) with clinical disease activity outcomes measured by change from BL in Clinical Disease Activity Index (CDAI), DAS of 28 joints using CRP (DAS28[CRP]), tender/swollen joint count in 28 joints (TJC28/SJC28), and pain by visual analog scale (VAS) at Weeks 12 and 24, were determined. Spearman correlations of maximum changes from BL in lipid levels and CRP through Week 12 were also determined.Results:Available fasting samples from 1,160 pooled patients (UPA 15 mg, n=386; UPA 30 mg, n=384; PBO, n=390) were included. Modest, but statistically significant, negative correlations were observed between maximum changes from BL in TC through Week 12 and change from BL in CDAI, DAS28(CRP), SJC28, and pain (VAS) at Week 12 with UPA 15 or 30 mg (Figure 1); similar trends were observed at Week 24. Significant correlations between changes in LDL-C and HDL-C and disease activity outcomes were also observed, but were not consistent across UPA doses and time points. No significant correlations were noted between changes in lipid levels and disease activity outcomes in the PBO group. Statistically significant weak negative relationships were observed between maximum changes from BL in lipid levels and CRP levels through Week 12 with UPA 15 mg (HDL-C and TC) or UPA 30 mg (LDL-C and TC) (Table 1).Conclusion:In this large pooled data set of patients receiving UPA, increases in lipid levels showed modest, but statistically significant, correlations with improvement in clinical disease activity outcomes in patients with cs/bDMARD-IR RA. These results add to evidence suggesting a relationship between systemic inflammation and lipid metabolism in patients with RA, which is modifiable with effective interventions, and reinforce the importance of monitoring for hyperlipidemia in these patients.

POS0702 PREGNANCY IN SLE PATIENTS TREATED WITH BELIMUMAB: EXPERIENCE FROM 3 ITALIAN CENTERS

Background:Belimumab (BEL) is a monoclonal antibody approved for SLE treatment but few data are available about its use before or during pregnancy.Objectives:Our study aims to describe pregnancies in SLE patients who have discontinued BEL before conception, at positive pregnancy test or during pregnancy.Methods:Data from prospectively-followed pregnancies (2014-2020) in SLE patients treated with BEL in 3 Italian centers where retrospectively collected, focusing on maternal disease activity, obstetric and neonatal outcome. Continuous data are expressed as median [min-max].Results:Thirteen SLE pregnancies were analyzed (median age at conception 32 [24-41] years; 77% spontaneous, 69% primigravidae). All patients had positive ANA and anti-dsDNA antibodies; 4 had anti-Ro antibodies (31%); 4 had anti-phospholipid antibodies (aPL; 1 single, 2 double and 1 triple positivity). Seven patients (54%) had a history of lupus nephritis (LN); 2 patients (15%) had a concomitant diagnosis of antiphospholipid syndrome (1 thrombotic-APS and 1 thrombotic+obstetric-APS).Ten (77%) pregnancies were planned and the use of BEL with regard to pregnancy was agreed with the patient during preconception counseling. At preconception visit, 8 patients were in remission while 5 had active disease (median SLEDAI 3 [0-8]).BEL (11 intravenous, 2 subcutaneous) was stopped in 2 cases before conception, in 7 at positive pregnancy test and in 4 during pregnancy (2 at 11th week, 1 at 22nd, 1 at 24th); median duration of treatment at discontinuation was 29 [4-68] months. Other treatments during pregnancy were: oral prednisone in 12 cases (92%); intravenous methylprednisolone in 1 (8%); hydroxychloroquine in 10 (77%); chloroquine in 1 (8%); azathioprine in 5 (39%); calcineurin inhibitors in 5 (39%); low-dose acetylsalicylic acid in 10 (77%); low molecular weight heparin in 9 (69%).Three flares occurred during the 3rd trimester in patients who stopped BEL at positive pregnancy test.Live-births occurred in 92% of the pregnancies. A patient with thrombotic+obstetric-APS and LN, underwent assisted reproductive technology (embryo donation) and developed eclampsia (25thweek), an urgent cesarean section was performed and the newborn died after 3 days. One pre-eclampsia occurred in a patient with history of LN, double aPL positivity and active disease. One miscarriage at 11th week occurred; no early miscarriages (&lt;10th week) were recorded. Pregnancy complications and outcomes are reported in Table 1.Table 1.Pregnancy complications and outcomes according to the timing of discontinuation of BEL.BEL STOPPED PRECONCEPTIONALLY(2)BEL STOPPED AT POS PREGNANCY TEST(7)BEL STOPPED DURING PREGNANCY(4)Pre-eclampsia0/20/71/4 (25%)Eclampsia0/20/71/4* (25%)Gestational Diabetes0/21/7 (14%)0/4IUGR0/21/7 (14%)1/4* (25%)pPROM/PROM0/20/71/4 (25%)Live birth1/2 (50%)7/7 (100%)4/4 (100%)Severe pre-term birth(≤ 34thweek)0/20/71/4* (25%)Late pre-term birth(35th- 37thweek)0/23/7 (43%)0/4Small for Gestational age neonate0/24/7 (54%)1/4 (25%)Late miscarriage (&gt;10thweek)1/2 (50%)0/70/4Perinatal death0/20/71/4* (25%)IUGR: IntraUterine Growth Restriction; PROM: Premature Rupture of Membrane; pPROM: pretermPROM; *in the same patient (history of thrombotic and obstetric-APS and lupus nephritis) who underwent Assisted Reproductive Technologies (embryo donation).No malformations were recorded. Two newborns were transferred to the Intensive Care Unit (1 for milk protein intolerance and 1 for desaturation).Eight newborns received vaccinations according to national schedule (missing data for 3). Five newborns were breastfed, 1 received formula milk and 5 mixed-feeding. BEL was resumed in 7/13 patients after pregnancy (in 4 cases for flare), after a median period of 5 [4-22] months.Conclusion:While more data are needed, this small series suggests that BEL might be a therapeutic option for SLE patients during pregnancy planning, similarly to other biological drugs used in chronic forms of arthritis.Disclosure of Interests:None declared

AB0373 PSYCHOMETRIC PROPERTIES OF OUTCOME MEASUREMENT INSTRUMENTS FOR LARGE VESSEL VASCULITIS: A SYSTEMATIC LITERATURE REVIEW

Background:Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two forms of chronic progressive large-vessel vasculitis (LVV) of unknown etiology. In 2016, the OMERACT Vasculitis Working Group proposed the development of a Core Domain Set of outcome measures for LVV including organ and arterial function, fatigue, pain, biomarkers, and death (1). Understanding the psychometric properties of outcome measurement instruments is essential when selecting among instruments to use in research; a summary of such properties for measures of LVV has not been developed.Objectives:To systematically review and summarize the psychometric properties of outcome measurement instruments used to measure the domains of the OMERACT core domain set for LVV.Methods:A comprehensive search of several databases (Medline, EMBASE, Cochrane, among others) from inception to July 14, 2020 was conducted. Articles were included if they covered psychometric properties of instruments used in LVV. Following the COSMIN and OMERACT frameworks, different psychometric properties (validity, inter- and intra-observer reliability, sensitivity to change, and feasibility) of outcome measurement instruments used in LVV (GCA and TAK) were assessed. Risk of bias was assessed according to the COSMIN checklist.Results:Among the 3534 articles identified, 15 studies focusing on the development or validation of psychometric properties on LVV met the predefined criteria. Two were development studies and 13 were validation studies. These studies provided information on 13 instruments: 5 instruments specific to TAK, 2 specific to systemic vasculitides, and 6 general, non-disease-specific instruments. No instruments specific to GCA were identified.Of the main psychometric properties assessed in the included studies, 40% had a low, 47% had moderate, and 13% had high risk of bias. Construct validity was the property most frequently assessed (in 93% of the tools) (Figure 1).In TAK, the Indian Takayasu Clinical Activity Score 2010 (ITAS2010) showed good consistency (r=0.97), reliability (intra-observer, ICC=0.60; inter-observer, ICC=0.92) and validity (correlation with Physician Global Assessment (PGA) (r=0.73)) for disease activity. Regarding disease damage, the Disease Extent Index-Takayasu (DEI-Tak) showed good validity (correlation with NIH score 94%, k=0.85). Non-specific vasculitis instruments such as the Vasculitis Damage Index (VDI) and the Birmingham Vasculitis Activity Score (BVAS) showed moderate validity in the assessment of disease damage in GCA (cumulative glucocorticoid dose and disease duration, r=0.30 and r=0.29) and TAK (cumulative glucocorticoid dose and disease duration, r=0.29 and r=0.25) in the former and disease activity in GCA in the later (PGA, r=0.50).Six non-vasculitis-specific patient-reported outcomes (PROs) instruments were identified, all showing low to moderate validity in GCA/TAK.Conclusion:The psychometric properties of 13 outcome measures to study LVV covering the OMERACT domains of disease activity, damage, and patient-reported outcomes were assessed. ITAS2010, DEI-Tak, VDI, and BVAS were the instruments with better psychometric properties for disease activity and/or damage. Disease activity and/or damage instruments specific for GCA, and validated PROs for both GCA and TAK are needed.

POS1014 CENTRAL SENSITIZATION HAS MAJOR IMPACT ON QUALITY OF LIFE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Background:Maintaining optimal health-related quality of life (QoL) is the ultimate goal of treatment in axial spondyloarthritis (axSpA). Chronic pain has a large potential impact on QoL. Central sensitization (CS) may explain part of the chronic pain in axSpA. However, the role of central sensitization (CS) herein has only been studied to a limited degree and current axSpA guidelines pay little attention to identification and treatment of CS.Objectives:To explore the relationship between CS and QoL in axSpA.Methods:Consecutive outpatients with axSpA from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. CS was assessed with the Central Sensitization Inventory (CSI; 0-100), QoL with the AS Quality of Life questionnaire (ASQoL; 0-18) and disease activity with the AS Disease Activity Score (ASDASCRP). A high probability of CS was defined as CSI score ≥40 and active disease as ASDASCRP score ≥2.1. Patient characteristics and clinical assessments were compared between groups with CSI score &lt;40 and ≥40.(1) Multivariable regression analysis was conducted to investigate the relationship between CSI and ASQoL scores, correcting for potential confounders.Results:Of the 178 axSpA patients with available CSI score, 149 completed the ASQoL. Mean age of the 178 included patients was 47.4 ± 14.1 years, 78 (44%) were female, mean symptom duration was 21.4 ± 13.6 years and 88 (52%) were using bDMARDS. Mean CSI score was 38.0 ± 14.1, mean ASQoL 6.0 ± 5.3 and mean ASDASCRP 2.1 ± 1.0. CSI score ≥40 was significantly associated with higher mean ASQoL (9.7 vs. 3.3), higher mean ASDASCRP (2.6 vs. 1.7), female gender (60% vs. 29%) and more often entheseal involvement (61% vs. 26%) (Table 1).Table 1.Selection of patient characteristics, disease activity and clinical outcome variables for patients with axSpA, divided in subgroups for CSI score with a cutoff point of 40.CharacteristicsAll patientsn = 178CSI&lt;40n = 98 (55%)CSI≥40n = 80 (45%)Age (years)47.4 ± 14.148.7 ± 15.045.8 ± 12.7Female78 (44)27 (29)44 (60)*Symptom duration (years)21.4 ± 13.621.5 ± 13.521.2 ± 13.8HLA-B27+133 (79)70 (79)54 (79)Smoker45 (27)28 (32)15 (23)BMI (kg/m2)26.7 ± 5.026.2 ± 4.427.5 ± 5.8Completed higher education181 (71)48 (70)34 (76)Biological use88 (52)49 (52)39 (51)RDCI (0-9)0.0 (0.0 – 1.0)0.0 (0.0 – 1.0)0.0 (0.0 – 1.8)Peripheral arthritis210 (6)5 (6)5 (8)Entheseal involvement364 (40)23 (26)38 (61)*ASDASCRP2.1 ± 1.01.7 ± 0.92.6 ± 1.0*CRP (mg/ml)2.9 (1.1 – 6.8)2.6 (1.1-6.0)3.6 (1.4 – 7.0)ASQoL (0-18)6.0 ± 5.33.3 ± 3.69.7 ± 4.9*CSI (0-100)38.0 ± 14.128.0 (23 – 34)50.0 (43.0 –56.0)N/AValues are n (%), mean ± SD or median (IQR).1International Standard Classification of Education (ISCED) level &gt;4; 2Swollen Joint Count &gt;0; 3Maastricht Ankylosing Spondylitis Enthesitis Score &gt;0. *p&lt;0.001. ASDASCRP: Ankylosing Spondylitis Disease Activity Score; ASQoL: Ankylosing Spondylitis Quality of Life questionnaire; CRP: C-reactive protein; CSI: Central Sensitization Inventory; RDCI: Rheumatic Disease Comorbidity Index.Patients with low ASDASCRP (&lt;2.1) and also low CSI score (&lt;40) showed good QoL (median ASQoL 1.1). Patients with low ASDASCRP combined with high CSI score (≥40) and patients with high ASDASCRP (≥2.1) combined with low CSI score reported worse QoL (median ASQoL 5.6 and 4.1, respectively). Patients with high ASDASCRP and also high CSI score reported the worst QoL (median ASQoL 12.0). (Figure 1).Figure 1.ASQoL score in patients with axSpA with CSI score ≥40 and &lt;40, divided for ASDASCRP (cutoff 2.1)Additionally, in univariable analysis, the CSI score explained a large proportion of the variation of the ASQoL (R2=0.46). This association remained significant after correction for ASDASCRP, gender, symptom duration, entheseal involvement, smoking status, BMI category, educational level and comorbidities in multivariable analysis (CSI p&lt;0.001).Conclusion:In daily clinical practice, CS seems strongly related to patient-reported QoL in patients with long-term axSpA.

Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis through systematic review and meta-analysis

To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p < 10−5) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (− 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers. The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p < 10−5). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.

Mobile-phone-based e-diary derived patient reported outcomes: Association with clinical disease activity, psychological status and quality of life of patients with multiple sclerosis.

BackgroundThe applicability of mobile digital technology to promote clinical care of people with multiple sclerosis (pwMS) is gaining increased interest as part of the implementation of patient-centered approaches. We aimed at assessing adherence to a smartphone-based e-diary, which was designed to collect patient-reported outcomes (PROs). Secondary objectives were to evaluate the construct and predictive validity of e-diary derived PROs and to explore the various factors that were associated with changes in PROs over time.Materials and methodsIn this observational cohort study patients downloaded an MS tailored e-diary into their personal smartphones. Report of PROs was enquired once monthly for a period of one year through a smartphone-based application, using previously validated tools. An e-diary derived bodily function summary score (eBF) was defined as the sum of scores depicting vision, limbs function, pain, bowl/ bladder dysfunction, pseudobulbar affect and spasticity. Multiple linear regression and analysis of covariance were used to determine the association between PROs, clinician-reported outcomes (ClinROs) of disease activity and quality of life (QoL). Regression coefficient analysis was used to compare the slope of change in eBF before and after a relapse.Results97 pwMS downloaded the e-diary [Female: 64 (66%), EDSS 3.4±2.1]. 76 patients (78%) completed the 12-month study period. 53 patients (55%) submitted ≥75% of requested surveys. Anxiety was negatively associated with adherence to periodic PROs assessments by the e-diary. E-diary derived PROs were significantly correlated with corresponding functional system scores (0.38< r <0.8, P<0.001). eBF score significantly predicted QoL (β = -0.36, P = 0.001) while EDSS did not. Change in eBF score over time was independently associated with the occurrence of an MS relapse (F = 4.4, P = 0.04), anxiety (F = 6.4, P = 0.01) and depression (F = 5.1, P = 0.03). Individual regression slopes of eBF scores were significantly higher pre-relapse than post-relapse (3.0±3.3 vs. -0.8±2.0, P = 0.007).ConclusionAdherence of pwMS to recording in an e-diary collecting PROs was high. Changes in e-diary derived PROs over time predict clinical MS relapses on the group level and thus carry the potential of usage in clinical research as well as for improved MS care in real world setting.

Long-term outcome and predictors of long-term disease activity in natalizumab-treated patients with multiple sclerosis: real life data from the Austrian MS Treatment Registry

ObjectivesTo evaluate long-term effectiveness of natalizumab (NTZ) and to determine demographic, clinical, and radiological predictors regarding long-term disease activity (≥ 7 years) in a nationwide observational cohort, using data collected prospectively in a real-life setting.Materials and methodsWe analysed data from 230 patients from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), who had started treatment with NTZ at any time since 2006 and stayed on NTZ for at least 7 years without treatment gap of more than three months.ResultsEstimated mean annualised relapse rates (ARR) over a mean treatment period of 9.3 years were 0.07 for NTZ. Sustained EDSS progression for 12 weeks was observed in 36 (19%) patients and for 24 weeks in 31 (16.3%) cases. Sustained EDSS regression for 12 and 24 weeks was seen in 45 (23.7%) and 42 (22.1%) cases. The baseline parameters ≥ 1 Gadolinium-enhancing MRI lesion(s) [incidence rate ratio (IRR) of 0.409 (95% CI 0.283–0.593), p = 0.001], ARR ≤ 1 in the prior 12 month before treatment initiation with NTZ [IRR of 0.353 (95% CI 0.200–0.623), p = 0.001] and EDSS ≤ 1 [incidence rate ratio (IRR) of 0.081 (95% CI 0.011–0.581), p = 0.012] were significantly associated with a reduced relapse risk, whereas a disease duration ≤ 5 years increased significantly the ARR [IRR of 1.851 (95% CI 1.249–2.743), p = 0.002]. The only predictive baseline parameter for experiencing EDSS progression (sustained for 12 and 24 weeks) was age > 35 years [HR of 2.482 (95% CI 1.110–5.549), p = 0.027, and HR of 2.492 (95% CI 1.039–5.978), p = 0.041, respectively].ConclusionsThese real-life data show a stable disease course regarding relapse activity and disease progression under NTZ treatment for more than 7 years. The main predictors for disease activity were higher relapse rate before treatment initiation, higher disability, shorter disease duration and absence of Gadolinium-enhancing MRI lesions at baseline. Older age at NTZ start was the only significant risk factor for disease progression over long-term.

Effect of systemic steroid therapy in Graves' orbitopathy on regulatory T cells and Th17/Treg ratio.

Glucocorticoids are a mainstay treatment for Graves' orbitopathy, yet their exact mechanisms of action remain unclear. We aimed to determine whether the therapeutic effects of systemic steroid therapy in Graves' orbitopathy are mediated by changes in regulatory T lymphocytes (Tregs) and T helper 17 lymphocytes (Th17). We assessed Treg and Th17 levels in the peripheral blood of 32 patients with active, moderate-to-severe Graves' orbitopathy who received 12 weekly pulses of methylprednisolone, and determined their association with disease severity, disease activity, and treatment outcomes. The acute orbitopathy phase was confirmed based on clinical evaluation and magnetic resonance imaging, and assessed using the clinical activity score (CAS). The severity of the disease was classified according to ETA/EUGOGO guidelines, and quantified based on the total eye score. Treatment response was determined based on specific criteria (e.g., changes in CAS score, diplopia grade, visual acuity, etc.). Treg and Th17 cells were identified using flow cytometry. Methylprednisolone treatment improved the activity of the disease and altered the Th17/Treg balance (i.e., the percentage of Tregs decreased while the number of Th17 cells remained unchanged). There was no association between the Treg/Th17 ratio and the activity and severity of the disease or the treatment response. Therapeutic effects of steroid therapy in Graves' orbitopathy are not mediated by Treg and Th17 alterations in the peripheral blood. The decrease in peripheral Treg percentage is likely a consequence of the non-specific effects of steroids and does not impact clinical outcome.

Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Utero-placental and cerebrovascular indices in pregnant women with systemic lupus erythematosus: Relation to disease activity and pregnancy outcome

Aim of the workTo assess maternal and fetal vascular indices in SLE patients during pregnancy, and the impact of disease activity on these vascular indices. Patients and methods30 pregnant SLE patients and 30 age -matched healthy females with uncomplicated pregnancies were assessed during the third trimester using ultrasonography (US) and Doppler study to detect fetal biometry, the uterine, umbilical (UA) and fetal middle cerebral (MCA) arterial resistance (RI) and pulsatility (PI) indices, as well as cerebro-placental ratio (CPR). Disease activity was determined using the SLE Disease Activity Index (SLEDAI). ResultsThe mean uterine artery PI, RI and the UA-PI in SLE group were significantly higher than controls (p value < 0.001), but no significant difference as regards UA-RI (p = 0.68) between both groups. There was unilateral uterine artery notch in 20% and bilateral in 6.7% while it was absent in 73.3%. The MCA-PI was significantly lower in SLE group (p = 0.003), Where the MCA-RI showed higher values than control (p < 0.001). The CPR showed a lower significant values for SLE group compared to controls (p < 0.001), while the PR interval was significantly higher in SLE group (p = 0.006). Fetal biometry showed no significant difference between two groups apart from higher abdominal circumference (AC) values in controls (p = 0.01). There was no significant correlation between abnormal vascular indices or biometric parameters and SLEDAI score (p > 0.05). ConclusionPregnancies in SLE are associated with abnormal maternal and fetal vascular indices. Doppler US can identify at-risk pregnancies and optimize the time of delivery; confirming a good pregnancy outcome.

Gender-related differences in disease activity and clinical features in patients with peripheral psoriatic arthritis: A multi-center study.

This study sought to compare disease activity, clinical features, and patient-reported outcomes concerning anxiety, depression, fatigue, function, quality of life, and fibromyalgia between female and male patients with peripheral PsA in a Turkish population. This multi-center Turkish League Against Rheumatism (TLAR) Network study included 1038 patients (678 females, 360 males) diagnosed with peripheral PsA according to the CASPAR criteria. The demographic and clinic parameters of the patients were recorded. Disease activity was evaluated using the scores of DAS28 and cDAPSA. Remission, minimal disease activity (MDA), and very low disease activity (VLDA) were determined. Health Assessment Questionnaire (HAQ), Short-Form-36 (SF-36), Hospital Anxiety and Depression Scale (HAD), fatigue VAS (0-10), and Fibromyalgia Rapid ScreeningTool (FiRST) were used. Disease activity and patient-reported outcomes were compared in male and female patients, and the predictors of MDA for both genders were analyzed. The patients' mean age was 47.6years (SD: 12) for females and 46.3years (SD: 12.3) for males. In terms of DAS28 and cDAPSA, female patients had significantly higher disease activity scores, while male patients had significantly higher remission rates (P<0.05). There was a significant difference in the rate of MDA in favor of males (P<0.05), but not in VLDA. The incidences of dactylitis, enthesitis, tenosynovitis, and inflammatory bowel disease were similar in male and female patients, except for spondylitis, which was higher in males (P<0.05). Overall, although there was no significant between-group difference in age and disease duration, female patients had significantly higher BMI and late-onset disease (P<0.05). Female patients had higher HAD, HAQ, and FiRST and lower SF-36 scores than males (P<0.05). In both male and female patients, the disease activity score of cDAPSA was significantly correlated with the scores of FiRST, HAD, VAS-F, and HAQ (P<0.05). In regression analysis, tender joint count, swollen joint count, PASI, pain VAS, and enthesitis were the MDA predictors in both genders. In patients with peripheral PsA, males are more likely to develop spondylitis while other extraarticular manifestations are similar. Female patients appear to have lower rates of remission and MDA and higher levels of disease activity. Female patients experience a more severe course of PsA, with higher levels of pain and fatigue, lower quality of life, and increased functional limitations. The predictors of MDA, i.e., tender joint count, swollen joint count, PASI, pain VAS, and enthesitis are similar between the two genders.

The effect of intravenous golimumab on health-related quality of life and work productivity in patients with active psoriatic arthritis: results of the Phase 3 GO-VIBRANT trial

Introduction/objectivesTo evaluate changes in health-related quality of life (HRQoL) and productivity following treatment with intravenous (IV) golimumab in patients with psoriatic arthritis (PsA).MethodsPatients were randomized to IV golimumab 2 mg/kg (n=241) at Weeks 0, 4, then every 8 weeks (q8w) through Week 52 or placebo (n=239) at Weeks 0, 4, then q8w, with crossover to IV golimumab 2 mg/kg at Weeks 24, 28, then q8w through Week 52. Change from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, and the Work Limitations Questionnaire (WLQ) was assessed. Relationships between these outcomes and disease activity and patient functional capability were evaluated post hoc.ResultsAt Week 8, change from baseline in EQ-5D-5L index (0.14 vs 0.04), EQ-VAS (17.16 vs 3.69), daily productivity VAS (−2.91 vs −0.71), and WLQ productivity loss score (−2.92 vs −0.78) was greater in the golimumab group versus the placebo group, respectively. At Week 52, change from baseline was similar in the golimumab and placebo-crossover groups (EQ-5D-5L index: 0.17 and 0.15; EQ-VAS: 21.61 and 20.84; daily productivity VAS: −2.89 and −3.31; WLQ productivity loss: −4.49 and −3.28, respectively). HRQoL and productivity were generally associated with disease activity and functional capability, with continued association from Week 8 through Week 52.ConclusionIV golimumab resulted in early and sustained improvements in HRQoL and productivity from Week 8 through 1 year in patients with PsA. HRQoL and productivity improvements were associated with improvements in disease activity and patient functional capability.Key Points• In patients with active psoriatic arthritis (PsA), intravenous (IV) golimumab improved health-related quality of life (HRQoL) and productivity as early as 8 weeks and maintained improvement through 1 year• Improvements in HRQoL and productivity outcomes in patients with PsA treated with IV golimumab were associated with improvements in disease activity and patient functional capability outcomes• IV golimumab is an effective treatment option for PsA that can mitigate the negative effects of the disease on HRQoL and productivity

Contraceptive Prevalence and Consulting Service in Women with Systemic Lupus Erythematosus: A Cross-Sectional Study.

Systemic lupus erythematosus (SLE), often affects women of childbearing age. Family planning consultation is a major aspect of medical care in these patients because of the risk of disease activation and poor pregnancy and fetal outcomes. The aim of the present study was to evaluate contraceptive prevalence and consulting service in women with SLE. In a cross-sectional study, a total of 144 female patients with SLE, ages 15-50, who were presented to rheumatology clinics in Sari, north of Iran, were evaluated. The study was conducted between March 2019 and May 2020. Patients' clinico-demographic profile and fertility information were obtained. Disease activity and damage were assessed by the systemic lupus erythematosus disease activity (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). One hundred and forty-four SLE patients of childbearing age participated in this study. From 102 patients with the possibility of pregnancy, 36(35.2%) received contraceptive consultations in last year. Withdrawal was the most prevalent contraceptive method (41.7%), followed by permanent (11.8%), and barrier methods (9%). There were no significant differences in age, disease duration, marriage duration, SDI or SLEDAI scores between the women who received or not received contraceptive counseling (P>0.05). Many SLE patients did not receive adequate information about contraception, and it may be associated with many adverse effects on disease activity and pregnancy outcomes. Therefore, contraceptive consultation as an important aspect of patient's management is strongly suggested.

Hepatic mosaic enhancement pattern correlates with increased inflammatory activity and adverse therapeutic outcomes in patients with Crohn's disease.

This study aimed to evaluate the role of hepatic mosaic enhancement pattern (HMEP) on computed tomography images in the disease activity and therapeutic outcome of Crohn's Disease (CD). Twenty-five CD patients with HMEP comprised the HMEP group, and 25 CD patients without HMEP, who had a similar onset age, sex, and disease course with those in the HMEP group, comprised the non-HMEP group. No underlying liver/biliary disease was observed in any of the patients. Clinical characteristics, laboratory test results, Lémann index, and CD endoscopic index of severity (CDEIS) were compared between the groups using the Student t-, Mann-Whitney U, Chi square, or Fisher's exact tests. Patients received top-down, step-up, or traditional treatment during the follow-up period. After the 1-year follow-up, therapeutic outcomes (active inflammation [CDEIS > 3.5 if the endoscopic data were available, or C-reactive protein level > 5mg/L if the endoscopic data were unavailable] or remission) were evaluated. The occurrence rate of fistulas/abscesses was higher in the HMEP group (84%, 21/25) than in the non-HMEP group (48%, 12/25) with no statistical significance (P = 0.056). The HMEP group showed a higher C-reactive protein level (P = 0.001), erythrocyte sedimentation rate (P = 0.013), and blood platelet count (P = 0.005). There was no significant difference in therapeutic strategies between the groups (P = 0.509). The HMEP group showed a significantly lower remission ratio after anti-inflammatory treatment than the non-HMEP group (P = 0.045). HMEP was correlated with increased inflammatory activity and adverse therapeutic outcomes in CD. This finding provided insights regarding novel markers of CD diagnosis and treatment.