Clinical Deep Remission Research Articles

Correlations between ultrafast power Doppler perfusion imaging variables and clinical disease activity in rheumatoid arthritis: potential applications for diagnosing and treating patients in deep clinical remission.

This study aimed to evaluate the ability of ultrafast power Doppler (PD) to assess disease activity in rheumatoid arthritis (RA) by examining the correlations between variables from ultrafast PD perfusion imaging and clinical measures of disease activity. Thirty-three RA patients underwent clinical assessments of disease activity and ultrasound scans of bilateral wrists using both ultrafast and conventional PD systems. A spatial singular value decomposition filter was applied to the ultrafast PD imaging. Singular vectors representing perfusion and fast flows were selected to produce perfusion images. All images were quantitatively analyzed with computer assistance and scored semiquantitatively (0-3) by a physician for synovial vascularity. The Pearson correlation coefficients between image variables and clinical indices were calculated. The correlation coefficients ranged from weakly to moderately positive between ultrafast PD variables and clinical indices (r=0.221-0.374, all P<0.05). The strongest correlations were observed for synovial PD brightness with the 28-joint Disease Activity Score based on C-Reactive Protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI). In patients within the deep clinical remission (dCR) subgroup, synovial PD brightness showed stronger correlations with DAS28-CRP, the Clinical Disease Activity Index, and SDAI (r=0.578-0.641, all P<0.001). The correlation coefficients between conventional PD variables and clinical indices were similar to those observed with ultrafast PD variables. Ultrafast PD imaging effectively extracts capillary blood signals and generates perfusion images. In the RA population, ultrafast PD variables exhibit weak-to-moderate correlations with clinical indices, with these correlations being notably stronger in dCR patients.

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn's Disease Patients.

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn's disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn's disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

Outcomes and Predictors of Sustained Remission After Drug Withdrawal in Pediatric Crohn Disease.

The primary aim of this study was to determine the proportion of pediatric Crohn disease (CD) subjects in sustained drug-free remission 52 weeks after stopping pharmacological therapy. We also aimed to explore the effects of the Crohn Disease Exclusion Diet (CDED) and microbiome composition on remission. We performed a prospective study following 18 CD patients ages 13-21 years in deep clinical remission withdrawing from immunomodulator (n = 7) or anti-TNFα (n = 11) monotherapy at two tertiary care centers. Stool for calprotectin and microbiome analyses was collected over 52 weeks. Participants followed either the CDED or free diet after drug withdrawal. The primary endpoint was sustained relapse-free drug-free remission (calprotectin <250 µg/g) at 52 weeks. Seventeen participants were followed through 52 weeks with 11 (64.7%) in sustained remission. There was no improvement in remission among participants following the CDED (5/9; 55.6%), P = 0.63. By 104 weeks, only 8 (47.1 %) participants remained off immunosuppressive therapies. Analysis of shotgun metagenomic sequence data revealed that taxonomic and gene function abundance in the gut microbiome was relatively stable for participants in remission and relapse. However, a predictive model incorporating gut microbial gene pathway abundance for amino sugar/nucleotide sugar metabolism and galactose metabolism from baseline samples predicted relapse at 52 weeks with 80% accuracy. After withdrawal of immunomodulator or anti-TNFα monotherapy among a small cohort of pediatric CD subjects in deep remission, nearly 65% sustained remission at 52 weeks. Baseline microbiome alterations predicted relapse. Large prospective studies are needed to better understand outcomes after treatment de-escalation.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BackgroundClinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region.MethodsRA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission.FindingsA total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission.InterpretationRemission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

Clinical Remission of Rheumatoid Arthritis in a Multicenter Real-World Study in Asia-Pacific Region

Background: Clinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates in Asia-Pacific region are lacking. We conducted a cross-sectional study to evaluate the clinical remission status and the associated factors in RA patients in Asia-Pacific region. Methods: RA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine associated factors of remission. Findings: A total of 2010 RA patients was included in the study, the overall remission rates were 62·31% (DAS28-CRP), 35·51% (DAS28-ESR), 30·78% (CDAI), 26·50% (SDAI), 24·71% (Boolean), and 17·06% (CliDR), respectively, and varied from sites to sites in the 11 countries. Biological disease-modifying antirheumatic drugs (bDMARDs) prescription rate was low (16·9%). Compared to patients in non-remission, patients in remission had higher rates of csDMARDs monotherapy, bDMARDs usage and lower rates of GC usage. The favorable factors were male sex, younger age, fewer comorbidities, less extra-articular manifestations (EAM), and use of bDMARDs, while treatment with GC was negatively associated with remission. Interpretation: Remission rates were low and varied in the Asia-Pacific region. Treatment with bDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region. Funding Information: Beijing Municipal Science and Technology Project (Z191100006619110), Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Peking-Tsinghua Center for Life Sciences. Declaration of Interests: None. Ethics Approval Statement: The study was approved by the ethics committee of each center.

Clinical conditions needed to acquire sustained functional remission in rheumatoid arthritis patients.

Treatments aimed at maintaining sustained clinical remission in rheumatoid arthritis (RA) patients have been recommended by several groups. Improvement and maintenance of functional status are also important for RA patients. The purpose of this study was to investigate the factors for maintaining long-term functional remission. RA patients with usual care without specific protocols were included. Disease activity score using 28-joint count C-reactive protein (DAS28-CRP), simplified disease activity index (SDAI) score, and Health Assessment Questionnaire Disability Index (HAQ-DI) score was calculated every 3 months for 1 year. Patients were divided into the HAQ-DI remission (REM) group and the HAQ-DI non-remission (NO-REM) group; time-averaged values of these parameters were compared between groups. Of the 205 patients, 154 fulfilled the remission criteria. Time-averaged DAS28-CRP and SDAI score were significantly lower in the REM group than in the NO-REM group (1.66 vs 2.59, 3.54 vs 10.68, respectively; p < 0.001). Subsequent receiver-operating characteristic (ROC) analysis for estimation of remission indicated a cut-off value of 1.65 for time-averaged DAS28-CRP and 2.85 for time-averaged SDAI score. Previous reports showed that fulfillment of clinical remission increases the possibility of functional remission; the probability of which is higher in patients with sustained clinical remission. Sustained clinical remission is required to achieve sustained functional remission; the criteria for clinical remission may be more stringent. Key Points • Sustained deep clinical remission was required to achieve sustained functional remission.

Predictors of long-term clinical remission in rheumatoid arthritis.

Little is known about possible predictors of long-term survival on biologic disease-modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission. The clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI-based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan-Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox-regression models. Eight-six patients were on SDAI remission, and the survival rate of bDMARDs since 'baseline-time' was 82.6% (MST=77.8 (95% CI: 69-86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST=86.3 (95% CI: 78-95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST=56.9 (95% CI: 45-69) months; P=.008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST=81.8 (95% CI: 73-91) months) than patients who were not taking MTX (66.7% (MST=55.3 (95% CI: 40-71) months) (log-rank 4.72, P=.03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10-0.93) and methotrexate co-therapy (HR 0.34, 95% CI: 0.12-0.98) were independently associated with a lower risk of bDMARD discontinuation. Among RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD.

Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis.

Background:Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA.Methods:This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months.Results:In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ2 = 3.937, P = 0.047), SDAI (χ2 = 4.666, P = 0.031), and CliDR criteria (χ2 = 4.297, P = 0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8–72.3] months, Z = −2.295, P = 0.022).Conclusions:The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.

PTU-068 Dose Optimisation Using Drug and Antibody Levels Can Benefit 50% Patients Prescribed Anti TNF Therapy Compared to Empiric Dose Adjustment: Abstract PTU-068 Table 1

Introduction In 2014 therapeutic drug monitoring (TDM) for antiTNF was introduced to the Royal London Hospital. Approximately 170 IBD patients per month receive infliximab or adalimumab. Previous data have shown TDM and optimised antiTNF prescribing improves clinical outcomes. 1 We audited the impact of TDM on cost-effectiveness and clinical outcome after 9 months compared to predictions we made prior to the introduction of this service. 2 Methods All IBD patients on antiTNF who had TDM between November 2014 and July 2015 were identified retrospectively using pathology records. Ideal standards of care were defined prospectively for different drug and antibody results. Actual clinical actions and outcomes 3 months after TDM were recorded and compared with the defined ideal standards of care. Results 160 tests on 133 patients were identified in the study period including 74 patients on infliximab and 59 patients on adalimumab. 88% patients had Crohn’s disease and 10% had ulcerative colitis. Escalated dosing regimens (increased dose or frequency) were prescribed in 48% patients. In patients on escalated doses, 13% IFX and 33% ADA had unrecordably high drug levels. A further 8% IFX patients on escalated doses were in deep clinical remission (CRP Appropriate cessation of antiTNF took place in 75% IFX and 20% ADA patients. Appropriate dose escalation only took place in 36% IFX and 6% ADA patients with low levels and no antibodies. Conclusion Empiric prescribing based on clinical assessment alone leads to sub-optimal drug levels in around 50% patients. The introduction of antiTNF TDM has allowed rational dose optimisation with immediate savings and clinical benefits. In routine practice, delays in interpreting TDM impacted on dose optimisation and wasted resources. These data have led to local changes in practice to ensure all results are acted on promptly. References 1 Vaughn BP, Sandborn WJ, Cheifetz AS. Biologic concentration testing in IBD . Inflamm Bowel Dis 2015; 21 (6):1435–1442. 2 Tandiari T, et al . PTH-083 Selective monitoring of antiTNF drug levels and antibodies will reduce short-term prescribing costs and provide early personalised tailoring of antiTNF therapy in routine IBD practice. Gut 2015; 64 (Suppl 1): A443. Disclosure of Interest P. Harrow: None Declared, C. Skinner: None Declared, T. Hoque: None Declared, A. Ibarra: None Declared, J. Lindsay Grant/research support from: MSD, Takeda and Hospira, Consultant for: MSD, Takeda, Abbvie, Napp, Hospira and Celltrion

P319a. Deep clinical remission in patients with Ulcerative Colitis: Evaluating the effects of vedolizumab on various combinations of endoscopic and patient-reported outcomes

P319a. Deep clinical remission in patients with Ulcerative Colitis: Evaluating the effects of vedolizumab on various combinations of endoscopic and patient-reported outcomes

PTU-072 Outcomes Of The Use Of Infliximab And Adalimumab In Patients With Crohn’s Disease At A District General Hospital

IntroductionInfliximab (IFX) and adalimumab (ADA) are licensed for the treatment of severe Crohn’s disease (CD). NICE recommends patients should receive these agents as a planned course of treatment for 12...

A prospective study of infliximab withdrawal after 12 months of treatment in patients with Crohn’s disease: how will NICE guidance affect patient care?

Infliximab is a biological agent that is licensed for the treatment of severe Crohn's disease. The annual cost of infliximab treatment is approximately pound 16,456 (excl VAT). In May 2010, the National Institute for Health and Clinical Excellence (NICE) recommended that patients should receive biological agents as a planned course of treatment only until treatment failure or until 12 months after the start of treatment, whichever is shorter. Patients should then have their disease reassessed to determine whether they still have active disease and whether ongoing therapy is still appropriate. We assessed the impact of the new NICE guidance on patient care by prospectively auditing patients who had been receiving infliximab for 12 months or more. The audit provided the opportunity for full disease reassessment and, for patients who were in clinical remission, the option to stop treatment. Disease was reassessed in 21 patients; a further 13 patients refused consent. Four patients were in deep clinical remission and discontinued infliximab. Implementation of the NICE recommendations on the use of infliximab in Crohn's disease is likely to be challenging in the face of significant resistance from patients who have an understandable fear of relapse. It might be more appropriate to discuss treatment withdrawal when high-quality evidence is available to support this management option.

Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease

Adalimumab is a fully human monoclonal antibody targeting tumour necrosis factor with proven efficacy in the treatment of Crohn's disease (CD). To investigate the predictors of medium-term clinical efficacy and mucosal healing during adalimumab therapy, in patients with CD, in specialised centres approved for biological therapy in Hungary. Data capture of the 201 CD patients was standardised and prospective (male/female: 112/89, median age: 33.0 years, duration: 8 years). Previous infliximab therapy had been administered in 48% of patients, concomitant steroids in 41%, azathioprine in 69% and combined therapy in 27% of patients. Overall clinical response and remission rates at 24 weeks were 78% and 52%, respectively; at 52 weeks were 69% and 44%, respectively. Endoscopic improvement and healing were achieved in 43% and 24% of patients. In a logistic regression model, clinical efficacy and CRP at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, whereas CRP at week 12, clinical remission at week 24, inflammatory parameters and nonsmoking were associated to endoscopic improvement/healing. Intensification to weekly dosing was needed in 16% of patients. Parallel azathioprine therapy and clinical remission at week 12 were inversely associated with dose escalation. Clinical efficacy and normalised CRP at week 12 (early deep clinical remission) are associated with medium-term clinical efficacy and mucosal healing during adalimumab therapy, whereas need for combined immunosuppression at induction and smoking status are predictors for non-response. Parallel azathioprine therapy may decrease the probability for dose escalation.