Lung Involvement in Patients with Ulcerative Colitis: Relationship between Exhaled Nitric Oxide and Lung Function.

Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airway involvement. A reduction in CO diffusing capacity and functional alterations in small airways have been described. An extended analysis of fractional exhaled nitric oxide (FeNO) may distinguish the sites of production, and the presence of small airway inflammation may be a useful, non-invasive marker for patient follow-up. The aim of our study was to compare the PFTs as well as FeNO and CANO values of UC patients with different clinical disease activities and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. We enrolled 42 adult outpatients at different clinical activity stages of UC (39 ± 13 years) and a healthy control group of 41 subjects (29 ± 3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100, and 200 mL/s) were collected. All patients performed pulmonary function tests (PFTs) with static volumes and diffusing capacity (DLCO). FeNO and CANO values were significantly increased in UC patients when compared with controls (p = 0.0008 and p < 0.0001, respectively) and were proportional to disease activity (FeNO class 3: 28.1 ppb vs. classes 1-2: 7.7 ppb; CANO values class 3: 8.6 ppb vs. classes 1-2: 2.7 ppb (p < 0.0001)). TLC and DLCO were significantly reduced in severe (Mayo 3) UC patients (p = 0.010 and p = 0.003, respectively). The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with disease activity, suggesting the need for an integrated approach in routine assessment.

Clinical disease activity index applicability in lupus arthropathy: Unraveling underdiagnosed joint activity.

INTRODUCTION: Lupus arthropathy (LA) ranges from arthralgia and non-deforming arthritis to severe forms such as Jaccoud-type deformities and mutilating arthritis. Considering the evolving concept of LA, measuring arthritis activity in lupus patients may require a more practical and sensitive tool other than the classical composite scores. METHODS: In this cross-sectional study, we evaluated the articular pattern of a sample of SLE patients which were divided into those that scored in articular domain on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and those with activity arthritis using the Clinical Disease Activity Index (CDAI). After all, we analyzed the association between CDAI and arthritis by SLEDAI-2K as well as its association with the presence or not of Jaccoud-type arthropathy (JA). RESULTS: A total of 127 patients with SLE were evaluated. According to SLEDAI-2K, 17 (13.4%) patients have scored in its joint criteria and 32 patients (25.19%) were considered to have some articular activity by CDAI. A total of 16 patients (50%) who scored some activity on CDAI did not score in articular domain of SLEDAI-2K. Also, the presence of Jaccoud-type arthropathy was significantly associated with arthritis activity according to the CDAI score (p = .014) but not with SLEDAI-2K joint criteria (p = .524). CONCLUSION: The CDAI was not directly associated with the presence of arthritis by the joint criteria of SLEDAI-2K and the presence of JA was significantly associated with the CDAI but not with arthritis at SLEDAI-2K.

Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.

OBJECTIVE: Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. METHODS: Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. RESULTS: One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. CONCLUSION: The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.

Effectiveness and safety of intravenous golimumab with and without concomitant methotrexate in patients with rheumatoid arthritis in the prospective, noninterventional AWARE study.

BACKGROUND: Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients. METHODS: AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients. All treatment decisions were at the discretion of the treating rheumatologist. Effectiveness was evaluated by mean change in CDAI scores at Months 6 and 12. Safety was monitored through approximately 1 year. RESULTS: Among 685 golimumab-treated patients, 420 (61%) received concomitant MTX during the study and 265 (39%) did not receive MTX after enrollment; 63% and 72%, respectively, discontinued the study. Relative to golimumab without MTX, golimumab + MTX patients had shorter mean disease duration (8.7 vs 10.0 years) and a lower proportion received prior biologics (60% vs 72%); mean ± standard deviation (SD) baseline CDAI scores were similar (30.8 ± 15.1 and 32.6 ± 15.4). Mean ± SD changes from baseline in CDAI scores at Months 6 and 12, respectively, were similar with golimumab + MTX (- 10.2 ± 14.2 and - 10.8 ± 13.8) and golimumab without MTX (- 9.6 ± 12.9 and - 9.9 ± 13.1). The incidence of adverse events/100 patient-years (PY) (95% confidence interval [CI]) was 155.6 (145.6, 166.1) for golimumab + MTX and 191.2 (176.2, 207.1) for golimumab without MTX; infections were the most common type. The incidence of infusion reactions/100PY (95% CI) was 2.1 (1.1, 3.6) for golimumab + MTX versus 5.1 (2.9, 8.3) for golimumab without MTX; none were considered serious. For golimumab + MTX versus golimumab without MTX, rates/100PY (95% CI) of serious infections, opportunistic infections, and malignancies were 2.6 (1.5, 4.3) versus 7.0 (4.4, 10.6), 0.9 (0.3, 2.0) versus 2.6 (1.1, 5.0), and 3.0 (1.7, 4.7) versus 1.0 (0.2, 2.8), respectively. CONCLUSIONS: Mean change in CDAI score in the  golimumab without MTX group was generally similar to that of the golimumab + MTX group through 1 year, regardless of prior biologic therapy. Adverse events were consistent with the known IV golimumab safety profile. These results provide real world evidential data that may assist healthcare providers and patients with RA in making informed treatment decisions. TRIAL REGISTRATION: clinicaltrials.gov NCT02728934 05/04/2016.

Locomotive syndrome in rheumatoid arthritis patients during the COVID-19 pandemic.

This study aimed to longitudinally evaluate the development of locomotive syndrome (LS) in rheumatoid arthritis (RA) patients during the COVID-19 pandemic using the 25-question Geriatric Locomotive Function Scale (GLFS-25). Subjects were 286 RA patients (female, 70.6%; mean age, 64.2 years) who had GLFS-25 and Clinical Disease Activity Index (CDAI) data available for a 1-year period during the COVID-19 pandemic and who did not have LS at baseline. Associations between subject characteristics and development of LS were determined using logistic regression analysis. Among the 286 patients, 38 (13.3%, LS group) developed LS at 1 year after baseline. In the LS group, scores of the GLFS-25 categories "GLFS-5" and "Social activities" were significantly increased at 1 year relative to baseline. GLFS-5 is a quick 5-item version of the GLFS-25, including questions regarding the difficulty of going up and down stairs, walking briskly, distance able to walk without rest, difficulty carrying objects weighing 2 kg, and ability to carry out load-bearing tasks and housework. A significant correlation was also observed between changes in "Social activities" and that of "GLFS-5." Multivariable logistic regression analysis revealed that the development of LS was significantly associated with BMI (OR: 1.11 [95% confidence interval (CI): 1.00-1.22]) and CDAI (OR: 1.08 [95%CI: 1.00-1.16]) at baseline. Adequate exercise and tight control of RA disease activity are important for preventing the development of LS in view of restrictions on going out imposed during the COVID-19 pandemic. GLFS-5 is useful for evaluating the physical function of RA patients.

Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study.

BACKGROUND & AIMS: Clinical studies of using probiotics for managing ulcerative colitis (UC) in Jordan are rare. Therefore, we aimed to evaluate the effect of probiotic supplementation on the clinical disease activity and biochemical parameters in patients with mild-to-moderately active UC. METHODS: thirty mild-to-moderate ulcerative colitis patients were included and randomly assigned to participate in a double-blinded randomized study to receive the treatment (3 × 1010 of probiotic capsules [containing nine Lactobacillus and five Bifidobacterium species], or a placebo), and included in the intention-to-treat analysis. Only 24 completed the study and were included in the per-protocol analysis. Both groups were compared in terms of clinical disease activity and biochemical parameters at the beginning and the end of the study. Registered under ClinicalTrials.gov Identifier no. NCT04223479. RESULTS: There was a significant induction of remission in the probiotic group presented by improvement in the partial mayo score (PMS). Probiotic group had significantly lower stool frequency (0.00 ± 0.00 vs. 1.17 ± 1.19), global assessment (0.42 ± 0.51 vs. 1.00 ± 0.74, p = 0.035), and total PMS score (1.33 ± 0.49 vs. 3.42 ± 1.78). In terms of mean and percent of change in post-to pre-treatment values, there was a significant reduction in C-reactive protein, and an increase in hemoglobin, hematocrit, and RBC levels in the probiotic group (p < 0.05). Additionally, there was a significant reduction in the IgA level and an increase in IL-10 levels among the probiotic group compared to the placebo group (p = 0.039). CONCLUSIONS: The use of probiotic therapy had significantly induced remission in UC patients, this was evidenced by the improvement in the Partial Mayo score. Furthermore, probiotic therapy had an appropriate effect on changes in hemoglobin, hematocrit, C-reactive protein, IgA, and IL-10 levels. This study was registered at ClinicalTrials.gov with the number NCT04223479.

Immune checkpoint inhibitor-associated arthritis in advanced pulmonary adenocarcinoma: A case report.

BACKGROUND: With the wide application of immune checkpoint inhibitors (ICIs) in cancer treatment, immune-related adverse events occur frequently, involving almost all organs and systems. The incidence of ICI-associated arthritis (IA) is unknown. In most cases, IA is not serious and non-lethal. Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression. Here, we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma, causing permanent withdrawal of pembrolizumab, but the patient remained in complete remission (CR) 20 mo after the development of IA. CASE SUMMARY: An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo. He was finally diagnosed with advanced pulmonary adenocarcinoma, with programmed cell death 1 ligand 1 expression of 70%. The patient responded to pembrolizumab treatment and achieved CR, but IA occurred after the 5th cycle of pembrolizumab administration. Although non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed, arthralgia and joint swelling occurred. The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal. Clinical Disease Activity Index (CDAI) score, a traditional measure of arthritis activity, was 43. Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk. The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab. A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR. CONCLUSION: This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.

The correlation of ultrasound-detected synovitis in an individual small joint with overall clinical disease activity in patients with rheumatoid arthritis.

OBJECTIVES: To explore the correlation between the ultrasound-detected synovitis in each individual joint at metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) regions and the clinical disease activity in patients with rheumatoid arthritis (RA). METHODS: Clinical disease activity was assessed by disease activity score (DAS) based on 28-joint count and erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Gray scale (GS) and power Doppler (PD) synovitis was assessed by ultrasound semi-quantitatively. The correlation between clinical disease activity indices and synovitis score in each joint was assessed using Spearman's rank correlation test. RESULTS: 211 RA patients were included in this study. The whole GS scores of all MCP joints showed the highest correlation with each Clinical Disease Activity Index (r = 0.403-0.452, p < 0.01). Likewise, the whole PD scores of all MCP joints also showed the highest correlation with clinical disease activity (r = 0.332-0.396, p < 0.01). At individual joint level, the highest correlation of GS score with DAS28-ESR (r = 0.411, p < 0.01), DAS28-CRP (r = 0.459, p < 0.01), and SDAI (r = 0.444, p < 0.01) was observed in MCP3 joint while with CDAI (r = 0.421, p < 0.01) in MCP2 joint. The highest correlation of PD score with DAS28-ESR (r = 0.353, p < 0.01), DAS28-CRP (r = 0.399, p < 0.01), CDAI (r = 0.368, p < 0.01), and SDAI (r = 0.377, p < 0.01) was observed in MCP5 joint. CONCLUSIONS: The ultrasound-detected synovitis at MCP joints, especially MCP2, MCP3, and MCP5 joints, was best correlated with clinical disease activity in most RA cases, in contrast to PIP and MTP joints. Key Points • The correlation of ultrasound-detected synovitis in each individual joint with the clinical disease activity in RA patients is diverse among joint regions. MCP joints showed the best, in contrast to PIP and MTP joints.

Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis.

BACKGROUND: Rapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between the gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity. METHODS: We conducted a retrospective, observational cohort study on patients diagnosed with RA between 1988 and 2014. Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points approximately 6-12 months apart. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups: MCII+ (who achieved MCII; n = 12) and MCII- (who did not achieve MCII; n = 20). Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up. RESULTS: We found age to be the largest determinant of the overall compositional variance in the gut microbiome (R2 = 7.7%, P = 0.001, PERMANOVA). Interestingly, the next factor identified to explain the most variance in the gut microbiome was MCII status (R2 = 3.8%, P = 0.005). Additionally, by looking at patients' baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Eubacterium sp. 3_1_31. Notably, patients who achieved clinical improvement had higher alpha-diversity in their gut microbiomes at both baseline and follow-up visits. Functional profiling identified fifteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine, L-methionine, and tetrahydrofolate, to be differentially abundant between the MCII patient groups. Moreover, MCII+ and MCII- groups showed significantly different fold-changes (from baseline to follow-up) in eight microbial taxa and in seven biochemical pathways. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patients will achieve MCII (balanced accuracy = 90.0%, leave-one-out cross-validation), demonstrating potential clinical utility of gut microbiome profiles. CONCLUSIONS: Our findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for RA.

Incidence of Infusion Reactions and Clinical Effectiveness of Intravenous Golimumab Versus Infliximab in Patients with Rheumatoid Arthritis: The Real-World AWARE Study.

OBJECTIVE: Evaluate tolerability and effectiveness of golimumab-IV versus infliximab in patients with rheumatoid arthritis (RA) in a real-world setting. METHODS: AWARE, a prospective, real-world, pragmatic, observational, multicenter, phase 4 study, enrolled RA patients when initiating golimumab-IV or infliximab. Treatment decisions were made by the treating rheumatologist. The approved doses for RA are 2 mg/kg at weeks 0, 4, then Q8W for golimumab-IV and 3 mg/kg at weeks 0, 2, 6, then Q8W (dose escalation permitted) for infliximab. A prespecified formal interim analysis was conducted. The primary endpoint was the incidence of infusion reactions (any adverse event that occurred during or within 1 h of infusion) through week 52. Major secondary endpoints were mean change from baseline in CDAI at months 6 and 12 in biologic-naïve patients (non-inferiority margin in the CDAI = 6). Baseline characteristics were adjusted using propensity scores with inverse probability of treatment weights (IPTW). RESULTS: In the formal interim analysis (golimumab-IV, n = 479; infliximab, n = 354), the incidence of infusion reactions was significantly lower with golimumab-IV vs. infliximab (3.6 vs. 17.6%, p < 0.001, IPTW-adjusted). Among biologic-naïve patients, mean changes from baseline in CDAI at month 6 (- 9.5 golimumab-IV vs. - 10.1 infliximab) and at month 12 (- 9.4 golimumab-IV vs. - 10.1 infliximab) demonstrated non-inferiority. CONCLUSIONS: The proportion of patients with an infusion reaction was significantly lower with golimumab-IV vs. infliximab. Among biologic-naïve patients, mean change from baseline in CDAI at months 6 and 12 was non-inferior for golimumab-IV vs. infliximab. Compared with fixed-dose golimumab-IV, infliximab dose escalation did not provide any greater improvements in CDAI for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02728934.

MAGNIMS score predicts long-term clinical disease activity-free status and confirmed disability progression in patients treated with subcutaneous interferon beta-1a.

BACKGROUND: Subcutaneous (sc) interferon (IFN) ß-1a reduces relapse rates and delays disability progression in patients with MS. We examined the association of the year 1 Magnetic Resonance Imaging in MS (MAGNIMS) score with long-term clinical disease activity (CDA) -free status and confirmed disability progression in patients treated with sc IFN ß-1a in PRISMS. METHODS: Patients treated with sc IFN ß-1a three-times-weekly (22 or 44 µg; pooled data) were classified by MAGNIMS score (0, n = 129; 1, n = 108; 2, n = 130) at year 1. Hazard ratios (HR; 95% confidence intervals [CI]) for risk of CDA and confirmed Expanded Disability Status Score (EDSS) progression were calculated by MAGNIMS score for up to 15 years of follow-up. RESULTS: The risk of CDA was higher with a year 1 MAGNIMS score of 1 versus 0 (HR 1.82 [1.38-2.41]), 2 versus 0 (2.63 [2.01-3.45]) and 2 versus 1 (1.45 [1.11-1.89], all p < 0.0001). The same outcome was observed with the risk of confirmed EDSS progression (1 versus 0: 1.93 [1.23-3.02]; 2 versus 0: 2.95 [1.95-4.46]; 2 versus 1: 1.53 [1.05-2.23]; all p < 0.0001). CONCLUSION: In PRISMS, MAGNIMS score at Year 1 predicted risk of CDA and confirmed disability progression in sc IFN ß-1a-treated patients over up to 15 years. PRISMS-15 clinicaltrial.gov identifier: NCT01034644.

Clinical disease activity and flare in SLE: Current concepts and novel biomarkers.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality. Such outcomes impair quality of life and inflict a significant socioeconomic burden. Predicting changes in SLE disease activity could allow for closer monitoring and preemptive treatment, but existing clinical, demographic and serologic markers have been only modestly predictive. Novel, proactive approaches to clinical disease management are thus critically needed. Panels of blood biomarkers can detect a breadth of immune pathway dysregulation that captures SLE heterogeneity and disease activity. Alterations in the balance of pro-inflammatory and regulatory soluble mediators have been associated with changes in clinical disease activity and are detectable several weeks prior to clinical flare occurrence. A soluble mediator score has been highly predictive of impending flare in both European American and African American SLE patients, and this score does not require a priori knowledge of specific pathway activation in the patient. We review current concepts of disease activity and flare in SLE, focusing on the potential of novel blood biomarkers to characterize and predict changes in disease activity. Measuring the disordered immune response in SLE in this way promises to improve disease management and prevent organ damage in SLE.

The Validity and Sensitivity of Rheumatoid Arthritis Pain Scale on a Different Ethnic Group From Indian Rheumatoid Arthritis Patients.

OBJECTIVES: This study aims to assess pain in rheumatoid arthritis (RA) patients by using Rheumatoid Arthritis Pain Scale (RAPS) and to find its correlation with Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI). PATIENTS AND METHODS: The study included 100 RA patients (23 males, 77 females; mean age 43.22 years; range, 19 to 72 years) who were subjected to RAPS questionnaire for pain assessment and DAS28 and CDAI for disease activity assessment. Spearman's correlation coefficient was measured to assess the correlation of RAPS with DAS28 and CDAI. Cronbach's alpha (α) was also measured for each scale to assess reliability. RESULTS: The study group had a female to male ratio of 3.34:1. Mean values for RAPS, DAS28 and CDAI were 62.91, 5.59, and 25.24, respectively. RAPS was correlated with DAS28 and CDAI with correlation coefficients of 0.811 and 0.770, respectively. Cronbach's α for RAPS, DAS28 and CDAI were 0.892, 0.814, and 0.833, respectively. CONCLUSION: Rheumatoid Arthritis Pain Scale had a strong positive correlation with disease activity measures of DAS28 and CDAI. RAPS also showed good correlation with core data set measures hence merits its place in clinical practice.

Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab treatment in rheumatoid arthritis.

OBJECTIVES: We aimed to evaluate the association between the change in serum IL-6 during the clinical course of tocilizumab (TCZ) therapy and rheumatoid arthritis (RA) disease activity or occurrence of adverse events. METHODS: General laboratory data including serum IL-6 levels and physical findings were obtained every 4 weeks, and, in addition, at the time when any adverse events occurred. RESULTS: The proportion achieving Clinical Disease Activity Index (CDAI) remission at 52 weeks was significantly lower in 20 patients with serum IL-6 ≥ 30 pg/ml at 12 weeks than 24 patients with serum IL-6 < 30 pg/ml. In 17 patients with serum IL-6 ≥ 30 pg/ml at 24 weeks, the proportion achieving CDAI remission was also significantly lower than 27 patients with serum IL-6 < 30 pg/ml then. In these 17 patients, Disease Activity Score (DAS) 28-ESR and CDAI at 52 weeks were significantly higher than those with serum IL-6 < 30 pg/ml. Age- and sex-adjusted logistic regression analysis showed logIL-6 at 12 weeks to be a predictive factor for DAS28-ESR remission at 52 weeks. CONCLUSION: Serum IL-6 levels from 12 to 24 weeks after TCZ initiation better reflect the efficacy of TCZ at 52 weeks.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

BACKGROUND: Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). METHODS: The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1ß, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. RESULTS: Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. CONCLUSIONS: Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

Clinical and demographic factors associated with change and maintenance of disease severity in a large registry of patients with rheumatoid arthritis.

BACKGROUND: We examined models to predict disease activity transitions from moderate to low or severe and associated factors in patients with rheumatoid arthritis (RA). METHODS: Data from RA patients enrolled in the Corrona registry (October 2001 to August 2014) were analyzed. Clinical Disease Activity Index (CDAI) definitions were used for low (≤10), moderate (>10 and ≤22), and severe (>22) disease activity states. A Markov model for repeated measures allowing for covariate dependence was used to model transitions between three (low, moderate, severe) states and estimate population transition probabilities. Mean sojourn times were calculated to compare length of time in particular states. Logistic regression models were used to examine impacts of covariates (time between visits, chronological year, disease duration, age) on disease states. RESULTS: Data from 29,853 patients (251,375 visits) and a sub-cohort of 9812 patients (46,534 visits) with regular visits (every 3-9 months) were analyzed. The probability of moving from moderate to low or severe disease by next visit was 47% and 18%, respectively. Patients stayed in moderate disease for mean 4.25 months (95% confidence interval: 4.18-4.32). Transition probabilities showed 20% of patients with low disease activity moved to moderate or severe disease within 6 months; >35% of patients with moderate disease remained in moderate disease after 6 months. Results were similar for the regular-visit sub-cohort. Significant interactions with prior disease state were seen with chronological year and disease duration. CONCLUSION: A substantial proportion of patients remain in moderate disease, emphasizing the need for treat-to-target strategies for RA patients.

Rheumatoid arthritis-associated interstitial lung disease: lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity.

OBJECTIVE: To describe the association between rheumatoid arthritis disease activity (RA) and interstitial lung damage (inflammation and fibrosis), in a group of patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: A retrospective study of RA patients with interstitial lung disease (restrictive pattern in lung function tests and evidence of interstitial lung disease in high resolution computed tomography (HRCT)). Patients were evaluated to exclude other causes of pulmonary disease. RA disease activity was measured with the CDAI index. Interstitial lung inflammation and fibrosis were determined by Kazerooni scale. We compared Kazerooni ground-glass score with the nearest CDAI score to HRCT date scan of the first medical evaluation at our institution. In nine patients, we compared the first ground-glass score with a second one after treatment with DMARDs and corticosteroids. Spearman's rank correlation coefficient was used to evaluate association between RA disease activity and the Kazerooni ground-glass and fibrosis scores. RESULTS: Thirty-four patients were included. A positive correlation between CDAI and ground-glass scores was found (rs=0.3767, P<0.028). Fibrosis and CDAI scores were not associated (rs=-0.0747, P<0.6745). After treatment, a downward tendency in the ground-glass score was observed (median [IQR]): (2.33 [2,3] vs. 2 [1.33-2.16]), P<0.056, along with a lesser CDAI score (27 [8-43] vs. 9 [5-12]), P<0.063. CONCLUSION: There is a correlation between RA disease activity and ground-glass appearance in the HRCT of RA-ILD patients. These results suggest a positive association between RA disease activity and lung inflammation in RA-ILD.

Comparative study between clinical disease activity index and simplified disease activity index by assessing the activity of rheumatoid arthritis / 中华风湿病学杂志

ObjectiveTo compare the clinical disease activity index (CDAI) and simplified disease activity index(SDAI) as well as disease activity score 28(DAS28) by assessing the activity of rheumatoid arthritis (RA) and to explore which one is better.MethodsTwo hundred RA patients were enrolled.Swelling joint counts (SJC),tenderness joint counts(TJC ),patient's and doctor's global assessment of disease activity based on visual analogue scale(PGA,PhGA),health assessment questionnaire(HAQ) were recorded and the erythrocyte sedimentation rate(ESR),C reaction protein (CRP) of each patient were tested.DAS28,CDAI,SDAI of all patients were calculated for all patients.Statistical analysiswas carried out by Pearson correlation for the association between DAS28 and the above parameters,as well as CDAI,and SDAI.We created 4 patient groups based on DAS28,CDAI and SDAI ranks and used kappa statistics to assess the level of overall agreement of different disease activity categories between any of the two indices above for individual patients.We assessed the discriminating validity using receiver operating characteristic(ROC) curve analysis to compare the ability of the CDAI and SDAI to discriminate betwecn patients with remission, low and moderate,high disease activity.ResultsOf all the patients,CDAI(17.2±11.1) and SDA[(19.1±11.6) were correlated with DAS28 (4.3±1.5),the correlation coefficients were 0.876,0.861 (P＜0.05) respectively.CDAI and SDAI were correlated with HAQ (0.6±0.7),as well as DAS28.The correlation coefficients were 0.522,0.523,and 0.482(P＜0.05).The Kappa of CDAI and SDAI was 0.777.The Kappa of CDAI and DAS28,SDAI and DAS28 were 0.482,0.394.The areas under ROC of CDAI and SDAI were 0.906,0.888 if DAS28 was used as the gold standard.ConclusionCDAI and SDAI as well as DAS28 can be used to assess the activity of RA and both are better correlated with HAQ than DAS28.Though there is no CRP in CDAI when compared with SDAI,CDAI has very goodoverall agreement with SDAI and the overall agreement of CDAI and DAS28 is better than SDAI and DAS28.In addition, CDAI is better in discriminating between patients with remission/low and moderate/high disease activity.So,CDAI is a simple,convenient,accurate,quick assessment tool and is suitable for daily application.

Anti-endothelial cell antibodies and central nervous system involvement in Behçet's disease

INTRODUCTION: Previous studies have detected the presence of anti-endothelial cell antibodies (AECA) in patients with Behçet's disease (BD). However, no real evidence exists whether these antibodies exert any influence on clinical presentation and/or activity of this disease. OBJECTIVES: To determine the frequency of AECA in patients with BD and analyze possible clinical associations. METHODS: 50 patients with BD who fulfilled diagnostic criteria were selected. Thirty-seven patients were females, and 13 were males; the mean age was 44 ± 9 years with a mean follow-up time of 10 ± 7.5 years. AECA were assayed by ELISA using ECV-304 cells as the antigenic substrate. The prevalence of AECA was determined, and their possible relationships with present and past clinical features were investigated. RESULTS: AECA were detected in the sera of 38 percent of the patients (IgG in 13, IgM in four, and IgG plus IgM in two). An association was observed between AECA and a previous history of central nervous system involvement (OR= 5.4, p= 0.03). This association was more evident for IgG-AECA (OR= 6.0, p= 0.02). A trend of an increased risk of aneurysms was also observed in patients with IgG-AECA (OR= 2.58, p= 0.77). None of the other clinical characteristics showed a relevant association with these antibodies. CONCLUSION: Our data suggest that IgG-AECA may be a marker of more severe lesions in patients with BD based on the higher frequency of previous central nervous system manifestations in patients who presently display circulating AECA.

INTRODUÇÃO: Estudos anteriores detectaram a presence de anticorpos anti-célula endotelial (AACE) em pacientes com doença de Behçet, porém não há nenhuma evidência se a presença destes anticorpos exerce alguma influência na apresentação clínica ou atividade da doença. OBJETIVOS: Determinar a freqüência de AACE em pacientes com doença de Behçet e analisar possíveis associações clínicas. MÉTODOS: Foram selecionados 50 pacientes que preencheram corretamente os critérios diagnósticos para a doença de Behçet. Trinta e sete pacientes eram do sexo feminino e 13 do sexo masculino, média de idade de 44 ± 9 anos e tempo médio de seguimento de 10 ± 7,5 anos. O AACE foram analisados por ELISA utilizando células ECV-304 como substrato antigênico. A prevalência de AACE foi determinada e foram investigadas possíveis relações com características clínicas atuais e pregressas. RESULTADOS: Os AACE foram detectados no soro de 38 por cento dos pacientes (13 na forma IgG, 4 IgM e 2 nas formas IgG e IgM). Observamos uma associação entre o AACE e história pregressa de envolvimento de sistema nervoso central (OR=5,4; p=0,03). Esta associação era mais evidente para o AACE na forma IgG (OR=6,0; p=0,02). Observamos também uma tendência de risco aumentado de aneurismas em pacientes com AACE na forma IgG (OR=2,58; p=0,77). Nenhuma outra característica clínica mostrou-se relevante com o anticorpo estudado. CONCLUSÃO: Nossos dados sugerem que o AACE na forma IgG pode ser uma marcador de lesão mais grave em pacientes com doença de Behçet baseado no fato de encontrarmos uma maior freqüência de história pregressa de manifestação de sistema nervoso central em pacientes com AACE circulante.