Clinical Disease Activity Index Score Research Articles

Influence of seasonal changes on disease activity and distribution of affected joints in rheumatoid arthritis

BackgroundPrevious studies suggest that RA activity is sensitive to seasonal changes. This study explored the influence of season on RA activity, particularly the distribution of affected joints, using a nationwide database in Japan.MethodsWe investigated 12,839 patients whose RA activity was recorded in spring (n = 3250), summer (n = 916), fall (n = 1021), and winter (n = 7652). Disease activity score (DAS) 28-CRP, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were used as indices of disease activity. Disease activity was also assessed according to DAS28-CRP scores (remission, low, moderate, or high). The affected joint distribution was investigated using novel joint indices (x, y, z), where x and y are indices for the upper and lower joints, respectively, and z is the index for large joint predominance.ResultsMean DAS28-CRP and median SDAI and CDAI scores were highest in spring and lowest in fall. There was a significant difference in the DAS28-CRP for fall versus spring and winter. Fall was associated with a higher remission rate, and spring and winter with high and moderate RA activity, respectively. Significant differences in x, y, SDAI, and CDAI scores were found for spring versus summer, fall, and winter, in addition to fall versus winter (except in y). There was no seasonal difference in the z index.ConclusionsRA activity in the upper and lower extremities may be highest in spring, followed by winter. Seasonal changes should be considered in patients with RA to better understand their symptoms.

Prevalence and Risk Factors of Subclinical Vertebral Fractures Among Women with Rheumatoid Arthritis

Introduction: Patients of rheumatoid arthritis (RA) are prone to osteoporosis and overt fractures. Subclinical vertebral fractures (SVFs) precede overt vertebral fractures. We studied prevalence and risk factors of SVFs among women with RA. Aim: To determine the prevalence of SVFs in women with RA and to study the various risk factors associated with presence of SVFs. Settings and design: Adult patients of RA attending the rheumatology clinic of medicine department at a tertiary teaching hospital in Delhi. One hundred eleven adult women with RA were included. Clinical assessment included anthropometry, Body Mass Index (BMI), duration of RA, disease activity using Clinical Disease Activity Index (CDAI), disease disability using Health Assessment Questionnaire (HAQ), and details of glucocorticoid (GC) use. Thoracic and lumbar vertebrae were graded for presence of VFs using the semi-quantitative method of Genant by two radiologists. Statistical analysis used: Simple descriptive statistics were used to describe prevalence of SVFs. Risk factors for SVFs were tested for significance using the Studentʼs t-test for quantitative variables and chi-square test for qualitative variables. Kappa statistics were calculated for assessment performed by the two radiologists. Two-sided alpha was set at 3 SVFs. Women with any SVF were significantly older as compared to women with no SVF. Fifty five percent of women using GCs had any SVF, while 44%, not using GC, had any SVF (P = ns). GC use, duration of RA, CDAI score, HAQ score, BMI, presence of RF, and anti-CCP were not different between women with and without SVFs. Kappa for inter-reader variability among the two radiologists was 0.98. Conclusions: This study provides evidence of very high prevalence of SVFs among women with RA. Traditional risk factors do not fully account for this enhanced risk.

Clinical Efficacy and Safety of Leflunomide in Egyptian Patients with Active Rheumatoid Arthritis: CLEAR Interim Results

Background: Worldwide, leflunomide is a commonly used Disease-Modifying Anti-Rheumatic Drugs (DMARDs). It can be used as a monotherapy or in combination with other DMARDs to inhibit the production of inflammatory cells and accordingly reduce inflammation. Objectives: CLEAR is a multi-centric study that aims to assess the clinical efficacy and safety of leflunomide as first-line and/or add-on therapy to other DMARDs with or without steroids in Egyptian patients with active Rheumatoid Arthritis (RA). Methods: Egyptian patients with active RA for whom leflunomide was prescribed at physicians’ discretion were observed for 12 weeks. Clinical Disease Activity Index (CDAI) score, and Health Assessment Questionnaire Disability Index (HAQ-DI) score were acquired thrice during this period. This study was registered on clinicaltrials.gov (NCT03599986). Results: Interim analysis of the data collected from 337 patients (in 21 centers) showed a statistically significant decrease in the mean total CDAI score throughout the first 12 weeks of treatment (p<0.001); as the mean ±SD score decreased from 36.60 ±14.90 at baseline to reach 16.16 ±9.84 at week 12 (% reduction: 61.16 ±14.36). A statistically significant decrease (p<0.001) was also observed in HAQ-DI, as the mean ±SD score decreased from 1.46 ±0.69 at baseline to reach 0.67 ±0.54 at week 12 (% reduction: 56.11 ±27.59). Conclusion: Results of the interim analysis suggest that treatment of Egyptian patients with active RA with leflunomide (as first-line and/or add-on therapy to other DMARDs with or without steroids) for 12 weeks may be effective in terms of CDAI score and HAQ-DI score reduction and may offer an alternative for patients who experienced resistance, inadequate response or intolerance to other DMARDs.

Tapering Janus kinase inhibitors in rheumatoid arthritis with low disease activity or remission: reality or dream?

In this issue of the journal, Takeuchi et al presented results of a baricitinib long-term extension study of patients who received baricitinib 4 mg for ≥15 months and maintained a...

Losartan, but not Enalapril and Valsartan, Inhibits the Expression of IFN-γ, IL-6, IL-17F and IL-22 in PBMCs from Rheumatoid Arthritis Patients.

Background:Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH.Objective:It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients.Methods:Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich.Results:Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28<3.2 and CDAI<10) had a better response to treatment. On the other hand, patients in moderate and severe activity had poor response to Losartan in cytokine inhibition.Conclusion:PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.

The expression of Semaphorin 5A in patients with rheumatoid arthritis and its effect on osteoclastogenesis

Objective: To investigate the clinical significance of soluble Semaphorin 5A(Sema 5A) in patients of rheumatoid arthritis(RA) and the effect of Sema 5A on osteoclastogenesis in RAW264.7 cells. Methods: (1)Soluble Sema 5A was detected in the serum of 62 RA patients, 30 osteoarthritis(OA) patients and 48 healthy controls(HC) by enzyme-linked immunosorbent assay(ELISA).The relationships between serum Sema 5A and disease activity, radiographic severity and laboratory parameters were investigated in RA patients.(2)RAW264.7 cells were treated with different concentrations of Sema 5A(0,0.5,1,2.5,5 μg/ml).After 7 days, tartrate-resistant acid phosphate(TRAP) staining was performed. The mRNA levels of TRAP, cathepsin-K and matrix metallopeptidase 9(MMP-9) were tested using real-time polymerase chain reaction (RT-PCR).(3)Bone resorption area of dentine slides cultured with RAW264.7 cells was calculated after Sema 5A(5μg/ml) treatment. Results: (1)The serum Sema 5A in RA patients[(5.24±0.59)μg/L] was significantly higher than those in healthy controls[(2.93±0.34)μg/L,P<0.01] and OA patients[(2.68±0.47)μg/L,P<0.05]. The Sema 5A level in RA patients was positively correlated with disease activity score with 28 joint using C-reactive protein(DAS28-CRP), clinical disease activity index (CDAI),C-reactive protein(CRP) and sharp scores(P<0.05 or P<0.01).In addition,the serum Sema 5A in RA patients with positive anti-cyclic citrullinated peptide(CCP) antibody was significantly greater than that of anti-CCP antibody-negative patients(P<0.05).(2)After RAW264.7 cells were treated with Sema 5A, the number of TRAP positive osteoclasts increased according to the increase of Sema 5A concentration with maximal effect at 5 μg/ml. Meanwhile, Sema 5A promoted mRNA expression of TRAP,Cathepsin-K and MMP-9.(3)Bone resorption area increased when RAW264.7 cells were treated with Sema 5A(5 μg/ml). Conclusions: Serum Sema 5A is elevated in RA patients and correlated with disease activity and radiographic severity. Sema 5A promotes osteoclastogenesis of RAW264.7 cells.

Structural damage progression in patients with early rheumatoid arthritis treated with methotrexate, baricitinib, or baricitinib plus methotrexate based on clinical response in the phase 3 RA-BEGIN study

The objective of this study was to evaluate structural damage progression based on clinical response in rheumatoid arthritis patients with no or limited prior disease-modifying anti-rheumatic drug treatment receiving the Janus kinase (JAK)1/JAK2 inhibitor baricitinib 4 mg, methotrexate (MTX), or the combination. Data from the phase 3 RA-BEGIN study were analysed post hoc. Proportions of patients with structural damage progression (change from baseline greater than the smallest detectable change in modified total Sharp score) at week 52 were evaluated based on sustained Disease Activity Score for 28-joint count with serum high-sensitivity C-reactive protein (DAS28-hsCRP) ≤ 3.2 or Simplified Disease Activity Index (SDAI) score ≤ 11; no formal statistical comparisons between treatments were performed to test these proportions. Baseline factors associated with risk of structural damage progression, including Clinical Disease Activity Index (CDAI) score, were identified using multivariate analysis. Patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to experience structural damage progression at week 52. In patients achieving these responses, structural damage progression was less likely with baricitinib monotherapy or plus MTX than with MTX monotherapy. In patients not achieving these sustained clinical thresholds, structural damage progression was less likely with baricitinib plus MTX than with either monotherapy. Independent of treatment, baseline factors significantly associated with increased risk of structural damage progression included higher hsCRP and CDAI score, smoking, female sex, and lower body mass index. In conclusion, patients achieving versus not achieving sustained DAS28-hsCRP ≤ 3.2 or SDAI score ≤ 11 were less likely to show structural damage progression, irrespective of treatment.

The Effectiveness of Intravenous Golimumab Administered Directly After Infliximab in Rheumatoid Arthritis Patients.

PurposeFor patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF.MethodsPatient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy.FindingsSignificant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p < 0.05). Limited changes were observed through the RAPID3 and PtGA.ConclusionsFindings from this study indicate that intravenous golimumab is effective in managing RA in a population of patients switching directly from infliximab (mean last dose 7.4 mg/kg).

High Disease Activity Is Associated with Self-reported Depression and Predicts Persistent Depression in Early Rheumatoid Arthritis: Results from the Ontario Best Practices Research Initiative.

We sought to determine if initial high disease activity or changes in disease activity contribute to persistent depression in early rheumatoid arthritis (ERA). We also determined if disease activity and depression is modified by sex. Depression was ascertained by self-report among patients enrolled in the Ontario Best Practices Research Initiative. The association between baseline disease activity, measured by the Clinical Disease Activity Index (CDAI), and persistent depression was evaluated with multivariate regression models, and effect modification by sex was tested. A general estimating equation assessed the association between change in CDAI over time and risk of depression. The sample of 469 ERA subjects was predominantly female (73%). At baseline, the prevalence of depression was 26%, and 23% reported persistent depression. After adjusting for potential confounders, higher baseline CDAI was associated with both baseline and persistent depression (OR 1.03, 95% CI 1.01-1.05). Female sex was an effect modifier of this relationship (OR 1.04, 95% CI 1.01-1.06). Maintaining a moderate or high CDAI score over 2 years also increased the risk of future depression. Depression in ERA is common and initial high disease activity is associated with the probability of depression and its persistence. This risk seems particularly modified in women with active disease and represents an area for targeted focus and screening. Future studies in ERA are needed to determine if intervening during the "window of opportunity" to control disease activity has the potential to mitigate the development and maintenance of adverse mental health outcomes, including depression.

Impact of Sustained Remission on the Risk of Serious Infection in Patients With Rheumatoid Arthritis.

ObjectiveThis retrospective analysis examined how sustained remission impacted risk of serious infections in patients with rheumatoid arthritis (RA) enrolled in a clinical registry.MethodsInclusion criteria included RA diagnosis, age ≥18 years, and ≥2 Clinical Disease Activity Index (CDAI) scores followed by a followup visit. Index date was the second of 2 visits in which a patient had sustained remission (CDAI ≤2.8), low disease activity (LDA; 2.8 < CDAI ≤10), or moderate‐to‐high disease activity (MHDA; CDAI >10). Followup extended from the index date until first serious infection (requiring intravenous antibiotics or hospitalization) or last followup visit. The crude incidence rate (IR) per 100 patient‐years for serious infections was calculated for the sustained remission, LDA, and MHDA groups. The multivariable‐adjusted incidence rate ratio (IRR) (adjusted for age, sex, and prednisone dose) compared serious infection rates across disease activity groups.ResultsMost patients were female (>70%); mean age was approximately 60 years. The crude IR (95% confidence interval [95% CI]) per 100 patient‐years for serious infections was 1.03 (0.85–1.26) in the sustained remission group (n = 3,355), 1.92 (1.68–2.19) in the sustained LDA group (n = 3,912), and 2.51 (2.23–2.82) in the sustained MHDA group (n = 5,062). Compared to sustained remission, the serious infection rate was higher in sustained LDA (adjusted IRR 1.69 [95% CI 1.32–2.15]). Compared to sustained LDA, the serious infection rate was higher in sustained MHDA (adjusted IRR 1.30 [95% CI 1.09–1.56]).ConclusionIn this study, lower RA disease activity was associated with lower serious infection rates. This finding may motivate patients and health care providers to strive for remission rather than only LDA.

Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

ObjectiveEpigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients.MethodsPeripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti‐cyclic citrullinated protein). Fluorescence‐activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome‐wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators.ResultsDifferential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type–specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified.ConclusionMethylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.

The Efficacy and Safety of Infliximab in Pediatric Crohnʼs Disease in China

BACKGROUND: Few studies have examined the efficacy and safety of infliximab (IFX) in pediatric Crohn's disease (CD) in China. This study aimed to investigate the response and remission rate of IFX, as well as the associated adverse events. METHODS: We collected data from CD patients who had received IFX 2 or more times from three hospitals in Shanghai from January 2007 to December 2016. The efficacy of IFX was observed, as well as the adverse events, relapse rate and retreatment efficacy. The overall risk factors related to IFX were also evaluated. RESULTS: Eighty-six patients participated in the study. With treatment, the patients demonstrated improved growth and nutrition indices and decreased disease activity. The clinical response rate was 91.9% and 88.2% at weeks 10 and 34, respectively. The sustained remission rates were 69.8% and 67.6% at weeks 10 and 34, respectively. The mucous healing rate was 19.3% at week 10 and 25.7% at week 34. Finally, 45 patients (66.2%) demonstrated durable responses, and 23 (33.8%) showed complete LOR. Adverse events related to IFX occurred in 55.8% of the patients, including allergic reactions in 17.4% and infections in 41.9%. Univariate analysis showed that a high pediatric clinical disease activity index score prior to IFX administration was a risk factor for IFX LOR. Continuation of concomitant azathioprine beyond induction was a protective factor for durable response. CONCLUSION(S): IFX is an effective treatment for CD in Chinese children; however, adverse events can occur. A comprehensive evaluation must be performed before each IFX infusion.

Association Between Pain Sensitization and Disease Activity in Patients With Rheumatoid Arthritis: A Cross-Sectional Study.

Pain sensitization may contribute to pain severity in rheumatoid arthritis (RA), impacting disease activity assessment. We examined whether pain processing mechanisms were associated with disease activity among RA patients with active disease. The study included 139 subjects enrolled in the Central Pain in Rheumatoid Arthritis cohort. Subjects underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at multiple sites, conditioned pain modulation, and temporal summation. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI) and its components. We examined cross-sectional associations between QST measures and disease activity using linear regression. Low PPTs (high pain sensitization) at all sites were associated with high CDAI scores (P ≤ 0.03) and tender joint counts (P ≤ 0.002). Associations between PPTs and patient global assessments were also seen at most sites. High temporal summation at the forearm (also reflecting high pain sensitization) was significantly associated with high CDAI scores (P = 0.02), patient global assessment scores (P = 0.0006), evaluator global assessment scores (P = 0.01), and tender joint counts (P = 0.02). Conversely, conditioned pain modulation (a measure of descending inhibitory pain pathways) was associated only with tender joint count (P = 0.03). High pain sensitization is associated with elevations in disease activity measures. Longitudinal studies are underway to elucidate the cause-effect relationships between pain sensitization and inflammatory disease activity in RA.

Examination of Patient-Reported Outcomes in Association with TNF-Inhibitor Treatment Response: Results from a US Observational Cohort Study.

Implementation of a treat-to-target strategy is challenging when the patient and physician prioritize different goals. This study aimed to "translate" improvements in Clinical Disease Activity Index (CDAI) to concepts that resonate with patients (such as pain, fatigue, morning stiffness) by examining the association between changes in disease activity and patient-reported outcomes (PROs) in a national cohort of patients with rheumatoid arthritis (RA) initiating their first biologic treatment. Patients in the Corrona registry with moderate or high disease activity (M/HDA) (defined by a CDAI score >10), prior use of at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), 12-month follow-up, and initiating their first tumor necrosis factor inhibitor (TNFi) between 1 January 2006 through 1 November 2015 were identified. Patients were stratified on the basis of CDAI during follow-up, and changes in PROs were compared with a test of trend using CDAI-defined groups. Of 1570 patients, 37% achieved sustained remission or low disease activity (remission/LDA), 15% had improving remission/LDA, 12% had worsening M/HDA, and 35% were in sustained M/HDA during 12-month follow-up. Those in sustained remission/LDA had greater magnitude of improvement in physical functioning, pain, fatigue, morning stiffness, patient's global assessment, and quality of life compared with patients in sustained M/HDA (p<0.001). Reduction in disease activity was associated with improvements in PROs, with the greatest improvements seen in those who achieved sustained remission/LDA. These results reinforce the benefits of a treat-to-target approach to RA care and may improve dialogue between patients and providers, support shared decision-making, and reduce "clinical inertia." Corrona, LLC.

Safety and effectiveness of subcutaneous tocilizumab in patients with rheumatoid arthritis in a real-world clinical setting

Objectives: The objective of this study is to evaluate the safety and effectiveness of subcutaneous tocilizumab (TCZ-SC) in a real-world clinical setting in Japan.Methods: This single arm, 26-week prospective observational study enrolled patients with RA who were either TCZ naïve or switched from TCZ-IV to TCZ-SC (TCZ-IV-SC group) (UMIN Clinical Trials Registry UMIN000011102). All patients received TCZ-SC 162 mg every 2 weeks and data were collected until week 26 or discontinuation.Results: Overall 784 (78.1%) were TCZ naïve and 219 (21.8%) were in the TCZ-IV-SC group. 70.9% received disease-modifying antirheumatic drugs at baseline. Adverse events (AEs) and serious AEs occurred in 28.2% and 4.9% of patients, respectively (TCZ-naïve: 29.5% and 5.2%; TCZ-IV-SC: 23.2% and 4.1%). Infections and infestations were the most common AEs (7.4%) and serious AEs (1.7%). Two TCZ-naïve patients died. TCZ-naïve patients had an improvement in median Clinical Disease Activity Index (CDAI) score and mean Disease Activity Score in 28 joints as measured by erythrocyte sedimentation rate (DAS28-ESR) from baseline to week 26. The TCZ-IV-SC group had similar median CDAI scores and mean DAS28-ESR over 26 weeks.Conclusions: There were no unexpected safety signals with TCZ-SC. TCZ-SC was effective in reducing disease activity in TCZ-naïve patients and maintaining remission in TCZ-IV-SC patients.

Interstitial lung disease in Egyptian patients with rheumatoid arthritis: Frequency, pattern and correlation with clinical manifestations and anti-citrullinated peptide antibodies level

IntroductionInterstitial lung disease (ILD) represents 13% of the overall mortality in rheumatoid arthritis (RA) patients. Aim of the workTo determine the frequency and pattern of ILD among RA patients, correlate it with clinical manifestations and with anti-citrullinated peptide antibodies (ACPA) titer. Patients and methodsThis study included 88 RA patients. ILD was diagnosed by high-resolution computed tomography (HRCT) and assessed by a severity score. Disease activity was assessed by clinical disease activity index (CDAI) and functional status by the modified health assessment questionnaire (MHAQ). Serum ACPA titer was assayed by ELISA. ResultsThe mean age of the patients was 50.15±9 years, disease duration was 10.2±6.2 years and they were 75 females and 13 males. ACPA was positive in 84 (95.5%). The frequency of ILD among RA patients was 71.6%. ILD patterns were: usual interstitial pneumonia (UIP) 62%, non-specific interstitial pneumonia (NSIP) 27%, others (Cryptogenic and mixed) in 11%. In RA-ILD, the mean ACPA titer was 225±121.5 U/mL versus 154.3 ±121.8 U/mL in RA only. In RA-ILD, ACPA titer negatively correlated with morning stiffness, CDAI, MHAQ and six-minute walk test (r=−0.3, p=.008, r=−0.6, p<.0001, r=−0.5, p<.0001 and r=−0.5, p<.0001 respectively), while it significantly correlated with IPF severity score (r=0.09, p<.0001) and erythrocyte sedimentation rate (ESR) (r=0.5, p<.0001). ConclusionILD frequency has increased among RA patients due to improved detection by HRCT. High titer of ACPA was associated with extent and patterns of severity of ILD in RA patients. When high ACPA titer is associated with low CDAI score, physician could suspect lung involvement.

Rebound in Measures of Disease Activity and Symptoms in Corrona Registry Patients with Psoriatic Arthritis Who Discontinue Tumor Necrosis Factor Inhibitor Therapy after Achieving Low Disease Activity.

Rebound may occur in patients with psoriatic arthritis (PsA) who discontinue TNF inhibitor (TNFi) therapy in low disease activity (LDA). Using physician and patient reports, we quantified rebound following TNFi discontinuation [defined as Clinical Disease Activity Index (CDAI) score > 10 or TNFi restart] and time to rebound in adults with PsA in LDA (CDAI score ≤ 10) at TNFi discontinuation. Rebound occurred in 73% (69/94) of patients soon after discontinuation (median time to rebound 8.0 mos, 95% CI 6.0-12.0). Rebound occurred frequently in patients with PsA after TNFi discontinuation. TNFi discontinuation after achieving LDA should be carefully considered.

Long-Term Effectiveness of Adalimumab in Patients with Rheumatoid Arthritis: An Observational Analysis from the Corrona Rheumatoid Arthritis Registry.

IntroductionCurrent recommendations for the management of rheumatoid arthritis (RA) focus on a treat-to-target approach with the objective of maximizing long-term health-related quality-of-life in patients with RA. Published studies from randomized clinical trials have reported limited data regarding the long-term efficacy and safety of adalimumab in patients with RA. This study aims to evaluate the long-term (10+ years) persistency and effectiveness of adalimumab in patients with RA in a real-world setting.MethodsIncluded in this study were biologic-naïve adults with RA initiating adalimumab during follow-up enrolled in the Corrona RA registry. More than 10 years of data on persistency of adalimumab and rheumatologist-supplied reasons for discontinuation were examined. Among patients who persisted on adalimumab over the years, clinical [e.g., clinical disease activity index scores (CDAI), physician global assessment, tender joint count, and swollen joint count] and patient-reported outcomes (PRO), such as physical function, pain, fatigue, and morning stiffness, were examined.ResultsOf 1791 biologic-naive patients treated with adalimumab who had ≥1 follow-up registry visit, 64.1% were still on therapy at 1 year and 10.2% were still on therapy by the end of year 12. Among patients who persisted on adalimumab for at least 1 year (77.1% female, mean age 53.9 years), 67.0% were in low disease activity (LDA)/remission (CDAI ≤10) and had clinically meaningful improvements from baseline in all clinical assessments and PROs. Initial improvements in LDA/remission and in clinical and PRO assessments observed at year 1 were sustained in those patients who remained on adalimumab over 10 years of follow-up. Among patients who discontinued adalimumab, 61.6% were not in LDA/remission and 41.9% switched to another biologic within 12 months after discontinuing adalimumab.ConclusionsReal-world data demonstrate a sustained effectiveness of adalimumab in the treatment of RA for patients who remained on therapy for 10 years.FundingCorrona, LLC and AbbVie.

Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis After Etanercept Discontinuation in the United Kingdom, France, and Germany

PurposeThe purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non–TNF-α biologic in the United Kingdom, France, and Germany. MethodsMedical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non–TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non–TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non–TNF-α inhibitors. FindingsPatient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non–TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (−6.3 vs −7.3, P = .06) relative to non–TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non–TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (−7.1 vs −5.8, P < 0.05) and comparable to that of non–TNF-α biologics (−7.1 vs −7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis. ImplicationsIn this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non–TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non–TNF-α biologics.

Interleukin-10-producing LAG3+ regulatory T cells are associated with disease activity and abatacept treatment in rheumatoid arthritis

BackgroundRegulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4+CD25−LAG3+ T cells (LAG3+ Tregs) and their association with rheumatoid arthritis (RA).MethodsLAG3+ Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects. The frequency of LAG3+ Tregs was evaluated in peripheral blood samples from 101 healthy donors and 85 patients with RA. In patients treated with abatacept, PBMC samples were analyzed before and after treatment. Naive CD4+ T cells were sorted and cultured in the presence of abatacept, followed by flow cytometric analysis and function assays.ResultsLAG3+ Tregs produced high amounts of IL-10 and interferon-γ, and they suppressed B-cell antibody production more strongly than CD25+ Tregs. Cell-to-cell contact was required for the suppressive function of LAG3+ Tregs. The frequency of LAG3+ Tregs was lower in patients with RA, especially those with higher Clinical Disease Activity Index scores. LAG3+ Tregs significantly increased after 6 months of abatacept treatment, whereas CD25+ Tregs generally decreased. Abatacept treatment in vitro conferred LAG3 and EGR2 expression on naive CD4+ T cells, and abatacept-treated CD4+ T cells exhibited suppressive activity.ConclusionsIL-10-producing LAG3+ Tregs are associated with the immunopathology and therapeutic response in RA. LAG3+ Tregs may participate in a mechanism for the anti-inflammatory and immune-modulating effects of targeted therapy for costimulation.