Definition Of Remission Research Articles

Redefining asthma management: Remodeling, rehabilitation and remission

Addressing the multifaceted aspects of asthma care calls for a thorough examination of new evidence regarding additional effects of treatments, as well as pioneering a paradigm shift in treatment outcomes. The concept of “people remodeling” unveils the complex interplay between changes in body weight and the use of oral corticosteroids, particularly highlighting how obesity, often a consequence of medication side effects, significantly influences asthma management. Simultaneously, integrating exercise into asthma treatment has undergone a transformative evolution, shifting from careful consideration to a pivotal cornerstone. Within the landscape of severe asthma treatment, the introduction of biological therapies has triggered a profound revolution by presenting the possibility of achieving clinical/complete remission, representing a departure from the conventional control goal. This review will discuss recent articles focusing on weight loss associated with biologics in patients with severe asthma, the effects of exercise on lung function in asthmatics and a consensus definition of clinical remission in severe asthma.

The OMERACT Giant cell arteritis Ultrasonography Score: a potential predictive outcome to assess the risk of relapse during follow-up.

To determine whether the OMERACT giant cell arteritis (GCA) Ultrasonography (US) Score (OGUS) change after treatment can be used for assessing the probability of relapse. Multicenter retrospective study of GCA patients referred to two US GCA fast-track clinics over 2 years. Patients underwent US evaluation at baseline, 3 and 6 months. EULAR definitions for remission and relapse were checked at 3 and 6 months. OGUS changes at 0-3 months and 0-6 months were compared among patients with and without relapse at 6 months, as well as those with and without remission at 6 months. A total of 76 patients were included (mean age 77.2 years, 55.3% females). Nineteen (26%) patients relapsed at 6-months, of whom 14(19.1%) showed a minor relapse. EULAR remission at 6 months was achieved by 32(43.8%) patients. The standardized mean difference of OGUS between baseline and 3 and 6 months was -0.25 and -0.38, respectively. OGUS significantly improved between baseline and 6 months (1.18 vs 0.99,p=0.004) and from 3-6 months (1.08 vs 0.99,p=0.04) in non-relapsing patients, whereas no significant changes at 3 (1.17 vs 1.17;p=0.736) and 6 (1.17 vs 1.21;p=0.343) months were observed in those who experienced relapse. Mean 0-6-month OGUS improvement was lower in patients who relapsed (-0.1 vs 0.16,p=0.037). Mean 0-6-month OGUS improvement was greater in patients who achieved remission at 6 months (0.28vs -0.07,p=0.001). The absence of OGUS improvement during follow-up in GCA may be used to assess the probability of relapse and the absence of remission at 6 months.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori-defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.

Clinical remission in severe asthma: lights and shadows on an ambitious goal.

The aim of this study was Describe the latest evidence related to the concept of clinical remission in patients with severe asthma, focusing on the lights and shadows of this concept. The idea of clinical remission in severe asthma patients brings about a significant shift in the way asthma is treated and managed. Although there has yet to be unanimous agreement among various scientific societies on the precise definition, this concept can be extremely useful in advancing the treatment of the disease. Asthma is a common respiratory condition that affects more than 300 million people globally. It has variable symptoms and severity levels, with about 10% of patients experiencing severe asthma. While there have been advancements in treatment, severe asthma poses significant challenges. Recent approaches have focused on achieving clinical remission, which goes beyond symptom control to address underlying inflammation and biological processes. Clinical remission criteria include the absence of symptoms, reduced medication usage, and normalized inflammatory markers. Various biologic therapies show promise, with some patients achieving remission. However, remission's definition varies globally, hindering standardization and a valid comparison. Standardizing remission criteria and refining predictive factors are crucial for effective asthma management. Overall, achieving clinical remission offers hope for improved long-term outcomes in severe asthma patients.

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force

ObjectiveTo derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. MethodsThe cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. ResultsThe Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. ConclusionscSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis

IntroductionExpert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. MethodsWe conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. ResultsIndividual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. ConclusionWhile the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Treatment response and clinical event-free survival in autoimmune hepatitis: A Canadian multicentre cohort study

We sought to identify predictors of outcome for people living with autoimmune hepatitis (AIH). We evaluated the clinical course of people with AIH across 11 Canadian centres. Biochemical changes were analysed using linear mixed-effect and logistic regression. Clinical outcome was dynamically modelled using time-varying Cox proportional hazard modelling and landmark analysis. In 691 patients (median age 49 years, 75.4% female), with a median follow-up of 6 years (25th-75th percentile, 2.5-11), 118 clinical events occurred. Alanine aminotransferase (ALT) normalisation occurred in 63.8% of the cohort by 12-months. Older age at diagnosis (odd ratio [OR] 1.19, 95% CI 1.06-1.35) and female sex (OR 1.94, 95% CI 1.18-3.19) were associated with ALT normalisation at 6 months, whilst baseline cirrhosis status was associated with reduced chance of normalisation at 12 months (OR 0.52, 95% CI 0.33-0.82). Baseline total bilirubin, aminotransferases, and immunoglobulin G (IgG) values, as well as initial prednisone dose, did not predict average ALT reduction. At baseline, older age (hazard ratio [HR] 1.25, 95% CI 1.12-1.40), cirrhosis at diagnosis (HR 3.67, 95% CI 2.48-5.43), and elevated baseline total bilirubin (HR 1.36, 95% CI 1.17-1.58) increased risk of clinical events. Prolonged elevations in ALT (HR 1.07, 95% CI 1.00-1.13) and aspartate aminotransferase (HR 1.13, 95% CI 1.06-1.21), but not IgG (HR 1.01, 95% CI 0.95-1.07), were associated with higher risk of clinical events. Higher ALT at 6 months was associated with worse clinical event-free survival. In people living with AIH, sustained elevated aminotransferase values, but not IgG, are associated with poorer long-term outcomes. Biochemical response and long-term survival are not associated with starting prednisone dose. Using clinical data from multiple Canadian liver clinics treating autoimmune hepatitis (AIH), we evaluate treatment response and clinical outcomes. For the first time, we apply mixed-effect and time-varying survival statistical methods to rigorously examine treatment response and the impact of fluctuating liver biochemistry on clinical event-free survival. Key to the study impact, our data is 'real-world', represents a diverse population across Canada, uses continuous measurements over follow-up, and our findings help inform risk stratification of patients. We provide evidence for treating clinicians, as well as those developing and evaluating new therapies, to seek evidence of good treatment response by keeping aminotransferase activity values within the reference range. Our results challenge the role of IgG as a marker of treatment response and if normalisation of IgG should remain an important part of the definition of biochemical remission. Our analysis further highlights that baseline markers of disease severity may not prognosticate early treatment response. Additionally, the initial prednisone dose may be less relevant for achieving aminotransferase normalisation. This is important for patients and treating clinicians given the relevance and importance of side-effects of treatment for patients.

Remission definitions guiding immunosuppressive therapy in rheumatoid arthritis: which is best fitted for the purpose?

ObjectiveTo assess which definition of remission best predicts good radiographic outcome (GRO) and good functional outcome (GFO) in rheumatoid arthritis, focusing the updated American College of Rheumatology/European Alliance of Associations...

Effect of Azithromycin on Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Anonymized, Placebo-Controlled Trial

BackgroundAsthma remission is a potential treatment goal. Research questionDoes adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared to placebo? Study Design and MethodsThis secondary analysis used data from the AMAZES clinical trial – a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids (OCS) during the previous six months evaluated at 12 months and Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (post-bronchodilator FEV1≥80% or post-bronchodilator FEV1≤5% decline from baseline) and complete remission (sputum eosinophils<3% plus the above criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. Results335 participants (41.5% male; median [Q1, Q3] age 61.01 [51.03, 68.73] years) who completed the 12-month treatment period were included in the analysis. Twelve months treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; p=0.032) and clinical remission plus lung function criteria (50.8% vs 37.1%; p=0.029) compared with placebo. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; p=0.058). Sensitivity analyses supported these findings. Baseline factors such as better asthma-related quality of life and absence of OCS burst in the previous year predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. InterpretationAdults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Defining Endoscopic Remission in Crohn’s Disease: MM-SES-CD and SES-CD Thresholds Associated With Low Risk of Disease Progression

ObjectiveWe assessed Modified Multiplier Simple Endoscopic Score for Crohn’s disease (MM-SES-CD) and SES-CD thresholds that are best associated with low likelihood of long-term disease progression. DesignData from 61 patients with early CD who participated in the CALM long-term extension study were used as the derivation cohort and validated using the McMaster IBD database (n=99). The primary outcome was disease progression (new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery) since the end of the CALM trial. Optimal MM-SES-CD and SES-CD thresholds were determined using the maximum Youden index. Receiver operating characteristic curve analyses compared threshold scores of remission definitions on disease progression. ResultsIn the derivation cohort, based on the maximum Youden index, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients in the derivation cohort with MM-SES-CD <22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p<0.001]. Similarly, a significantly greater number of patients with SES-CD ≥ 4 had disease progression compared to those with a SES-CD <4 [11/25 (44.0%) vs. 2/36 (5.6%), p<0.001]. Compared to other clinical or endoscopic remission definitions, which demonstrated poor to fair accuracy, MM-SES-CD <22.5 performed the best for predicting disease progression [AUC: 0.81 (95%CI: 0.68-0.94), p<0.001]. These thresholds were confirmed in the validation cohort. ConclusionsAchievement of MM-SES-CD <22.5 or SES-CD <4 in patients with ileocolonic or colonic CD is associated with low risk of disease progression and may be suitable targets in clinical trials and practice for endoscopic healing.

CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up

BackgroundTreatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.MethodsWe evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. Efficacy up to 2 years after CAR T-cell infusion was assessed by means of Definition of Remission in SLE (DORIS) remission criteria, American College of Rheumatology–European League against Rheumatism (ACR–EULAR) major clinical response, and the score on the European Scleroderma Trials and Research Group (EUSTAR) activity index (with higher scores indicating greater disease activity), among others. Safety variables, including cytokine release syndrome and infections, were recorded.ResultsThe median follow-up was 15 months (range, 4 to 29). The mean (±SD) duration of B-cell aplasia was 112±47 days. All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index. Immunosuppressive therapy was completely stopped in all the patients. Grade 1 cytokine release syndrome occurred in 10 patients. One patient each had grade 2 cytokine release syndrome, grade 1 immune effector cell–associated neurotoxicity syndrome, and pneumonia that resulted in hospitalization.ConclusionsIn this case series, CD19 CAR T-cell transfer appeared to be feasible, safe, and efficacious in three different autoimmune diseases, providing rationale for further controlled clinical trials. (Funded by Deutsche Forschungsgemeinschaft and others.)

Mirikizumab: A New Therapeutic Option for the Treatment of Ulcerative Colitis.

To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC). A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor, and UC. Information was also obtained from package inserts as well as published abstracts. Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed. Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%). Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC. Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile.

P409 Optimal endoscopic healing thresholds defined by MM-SES-CD &amp;lt; 22.5 and SES-CD &amp;lt; 4 are associated with low risk of disease progression in Crohn’s disease

Abstract Background After initiation of therapy in Crohn's disease (CD), it remains unclear what the optimal endoscopic healing (EH) threshold to target is using the SES-CD and the MM-SES-CD (Modified Multiplier Simple Endoscopic Score for Crohn’s disease). We assessed MM-SES-CD and SES-CD thresholds that are best associated with low likelihood of long-term disease progression. Methods Week 48 endoscopy videos from patients with CD who participated in the CALM long-term extension LTE study were obtained and re-read by central readers to obtain a SES-CD and MM-SES-CD score, which was used for the derivation cohort. A real-world validation was performed with data from 99 patients that had clinical response using a mixed cohort of biologic therapies from the McMaster IBD database. The primary outcome was disease progression, defined as a new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery since the end of the CALM trial for the derivation cohort, and over the observed period of follow-up for the validation cohort. The maximum Youden index was calculated to determine the optimal MM-SES-CD and SES-CD thresholds. Receiver operating characteristic curve analyses compared threshold scores of various remission definitions on disease progression. Kaplan-Meier survival curve analyses were performed to compare the time to disease progression from the end of study endoscopy in the derivation cohort. Results In the derivation cohort, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD &amp;lt;22.5 and SES-CD &amp;lt;4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients with MM-SES-CD &amp;lt;22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p&amp;lt;0.001]. Similarly, a significantly greater number of patients with a SES-CD ≥ 4 had disease progression compared to those with a SES-CD &amp;lt;4 [11/25 (44.0%) vs. 2/36 (5.6%), p&amp;lt;0.001]. Compared to other clinical or endoscopic remission definitions, obtaining a MM-SES-CD &amp;lt;22.5 at the end of the CALM study performed the best for predicting disease progression [AUC: 0.81 (95% CI: 0.68-0.94), p&amp;lt;0.001](sensitivity 76.9% (95% CI: 46.2-95.0), specificity 85.4% (95% CI: 72.2-93.9)). Compared to those with lower scores, patients with MM-SES-CD ≥ 22.5 (log-rank p&amp;lt;0.0001) and SES-CD ≥ 4 (log-rank p=0.0002) had a significantly greater probability of disease progression (Figure 1A/B). These findings were confirmed in the validation cohort (Figure 1C/D). Conclusion Achievement of MM-SES-CD &amp;lt;22.5 and SES-CD &amp;lt;4 was associated with low risk of CD progression and may be a suitable target for EH in clinical trials and practice. Our findings support that targeting EH may modify the natural course of CD.

P574 Clinical outcomes in extending of injection period of ustekinumab from every 8 to 12 weeks in patients with Crohn’s disease (CD-EXTEND Study)

Abstract Background De-escalation was a useful strategy for improving patient’s QOL and reduction of medical expenses. However, de-escalation of ustekinumab (UST) for the patients with Crohn’s disease (CD) has not been reported. The aim of this study was to elucidate clinical outcomes of de-escalation of UST. Methods This was a single-centre prospective observational study approved by the institutional review board of our hospital. CD patients who selected de-escalate UST treatment after administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks until 54 weeks were enrolled in this cohort. Primary endpoint was clinical remission rate at one year, including patients treated with re-escalation. Secondary endpoints were persistency of de-escalation of every 12 weeks and re-escalation effects of every 8 weeks. We also compared backgrounds and biomarkers including CRP, fecal calprotectin (FC) for persistent and non-persistent groups. Cut-off values of prediction for non-persistent was calculated by receiver operating characteristic (ROC) curve. Definition of clinical remission was CDAI&amp;lt;150 for CD. Results In total, 30 participants were included in the final analysis. Clinical remission rate at one year was 96.7% (29/30). Persistency of de-escalation at one year was 76.7% (23/30). Persistency after re-escalation was 85.7% (6/7). There was no difference between the backgrounds of persistent (n=23) and non-persistent groups (n=7). CRP titer at week 12 was significantly higher in non-persistent group than persistent group (Median 0.59 vs 0.17 mg/dL, p=0.021). FC titer at week 0, 12 and amount of change at week 24 was significantly higher in non-persistent group than persistent group (Median 660 vs 120 μg/g, p=0.021;1341 vs 61 μg/g, p=0.001; 528 vs 4 μg/g, p=0.04). Cut-off values of prediction for non-persistent from CRP at week 12, FC at week 0, 12 were 0.33 mg/dL, 314 μg/g, 581.5 μg/g, respectively. Conclusion De-escalation was feasible strategy for CD patients treated with UST. CRP and FC were good prediction biomarker for non-persistence

OP36 Risankizumab Versus Ustekinumab for the Achievement of Clinical Outcomes and Symptom Improvement in Patients With Moderate To Severe Crohn’s Disease: Results From the Phase 3b SEQUENCE Trial

Abstract Background The efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate to severe Crohn's disease (CD) refractory to prior anti-tumour necrosis factor (TNF)α therapy were compared in the SEQUENCE head-to-head study. Previously, wk24 CD activity index (CDAI) clinical remission rates (CDAI&amp;lt;150) were reported for 50% of pts (first primary endpoint);1 here, the efficacy of RZB versus (vs) UST for achieving wk24 clinical remission and other symptomatic improvements in the full pt population was assessed. Methods SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study in pts with moderate to severe CD (defined in Figure footnote) refractory to TNFα therapy. Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, week (wk)4 and wk8, then 360mg subcutaneous [SC] maintenance every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance starting at wk8) up to wk48. A mandatory steroid taper began at wk2. Randomisation was stratified by BL steroid use and number of failed anti-TNFs. Prespecified non-ranked endpoints included CDAI clinical response and stool frequency (SF)/abdominal pain score (APS) clinical remission (definitions in Figure footnote). CDAI clinical remission at wk48 was a ranked secondary endpoint. CDAI clinical remission at wks 8 and 24, and changes from BL in avg daily APS, SF, and CDAI, were evaluated post-hoc. Binary endpoints were analysed using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. Continuous endpoints were analysed using a mixed-effect model with repeated measures. All P values are nominal, except for wk48 CDAI clinical remission (ranked secondary endpoint). Results With RZB vs UST, respectively, greater rates of CDAI clinical remission (59.6% [152/255] vs 42.6% [113/265]; P=0.0001), SF/APS clinical remission (55.7% vs 41.1%; P&amp;lt;0.001) and CDAI clinical response (69.8% vs 54.3%; P&amp;lt;0.001) were observed at wk24; similar results were observed at wk48 (Figure). Mean BL APS in the RZB and UST groups was 1.9 (both groups), SF was 5.5 and 5.6, and CDAI was 309.4 and 310.1, respectively. Least square (LS) mean changes from BL in APS, SF, and CDAI were greater with RZB vs UST and observed early as wk8 (APS: -0.9 vs -0.8; SF: -3.0 vs -2.3; P&amp;lt;0.001; CDAI: -136.3 vs -117.1; P&amp;lt;0.05) (Figure). The safety profiles of RZB and UST were consistent with published results.1 Conclusion In this head-to-head study, improvements in symptomatic outcomes in pts with CD were greater with RZB than UST over 48 wks of treatment. 1doi.org/10.1002/ueg2.12474

Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study.

We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD. The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, and CVD incidence as any occurrence of non-fatal acute myocardial infarction, stroke, admission for angina or CVD death. Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission. Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol. ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.

Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression

ObjectivesTreatment targets in systemic lupus erythematosus (SLE) have been validated in unselected—in terms of severity—cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus...

Long-Term Effectiveness of Benralizumab in Eosinophilic Granulomatosis With Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disease characterized by eosinophilic tissue inflammation. Benralizumab, an anti-IL-5 receptor (anti-IL-5R) monoclonal antibody, induces rapid depletion of eosinophils; its longer-term effect in EGPA is unknown. To assess the real-world effectiveness and clinical remission rates of anti-IL-5R therapy in EGPA. We performed a retrospective cohort analysis of patients with EGPA, who commenced treatment with benralizumab. Clinical remission, assessed at 1 year and 2 years after the initiation of benralizumab, was defined as an absence of active vasculitis (Birmingham Vasculitis Activity Score of 0) and an oral corticosteroid (OCS) dose of ≤4 mg/d of prednisolone. "Super-responders" were defined as patients in remission and free of any significant relapses (asthma or extrapulmonary) over the preceding 12 months. The corticosteroid-sparing capacity of benralizumab, patient-reported outcome measures, and characteristics associated with clinical remission and super-responder status were also analyzed. A total of 70 patients completed at least 1 year of treatment with benralizumab, of whom 53 completed 2 years. Of 70 patients, 47 (67.1%) met the definition for clinical remission at 1 year, with a similar proportion in remission at 2 years. Excluding asthma-related relapses, 61 of 70 (87.1%) patients were relapse free at 1 year, and of the 53 who completed 2 years, 45 (84.9%) were relapse free. A total of 67.9% of patients no longer needed any OCS for disease control. No significant difference was seen between antineutrophilic cytoplasmic antibody (ANCA)-positive and ANCA-negative subgroups. In this real-world setting of patients with EGPA, treatment with benralizumab was well tolerated and resulted in corticosteroid-free clinical remission for the majority of patients.

Comparison of Remission Criteria in Patients with Rheumatoid Arthritis: Results from a Smart System of Disease Management Group.

This study aimed to compare the rates of disease remission evaluated using various remission criteria, including Boolean2.0, Boolean1.0, clinical disease activity index (CDAI), simplified disease activity index (SDAI), and disease activity score using 28 joints based on C-reactive protein (DAS28-CRP) in patients with rheumatoid arthritis (RA). A cross-sectional observational analysis was performed using data from patients with RA enrolled in a smart system of disease management group (SSDM). The clinical remission rates of RA patients estimated using the DAS28-CRP, CDAI, SDAI, Boolean1.0 and Boolean2.0 criteria were investigated. Variables were compared using the t-test, Mann-Whitney U-test, or chi-squared test. The agreement between Boolean remission and the DAS28-CRP, CDAI, or SDAI definitions of remission was assessed using McNemar's test with k coefficient of agreement. A total of 5619 patients were included in the analysis. The mean age of the patients was 56.33 (±13.01) years, with the majority being female (4491, 79.9%). The rates of remission, as assessed by Boolean2.0, Boolean1.0, DAS28-CRP, CDAI, and SDAI, were 16.6%, 9.7%, 35.2%, 9.1%, and 9.4%, respectively. Comparison with Boolean1.0 criteria revealed higher concordance between Boolean2.0 and DAS28-CRP remission and lower concordance with CDAI and SDAI, regardless of whether the analysis was conducted on the entire population or subgroups based on gender, age or disease duration. Additionally, the administration of different medications may have influenced the rate of Boolean2.0 remission. This study demonstrated a higher concordance between Boolean2.0 criteria and DAS28-CRP remission and a lower concordance with CDAI and SDAI when compared with Boolean1.0 remission criteria.

Usefulness in daily practice of the Systemic Lupus Erythematosus Disease Activity Index 2000 scale and the Systemic Lupus Erythematosus Disease Activity Score index for assessing the activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by high heterogeneity of clinical manifestations and an uncertain prognosis. Although the mortality rate due to SLE has decreased significantly in recent decades, there is still a need to find good tools to measure disease activity for early detection of exacerbations and treatment planning. Over the decades, more than a dozen disease activity scales/indicators have been developed, with the SLE Disease Activity Index (SLEDAI) being the most popular. More recently, the new SLE Disease Activity Score (SLE-DAS) has been introduced. This paper compares the two methods of assessing SLE activity, and presents the relevance of these scales in pregnant SLE patients and their use in formulating definitions of remission and low disease activity. The results show that the SLEDAI and the SLE-DAS are of comparable value in assessing SLE activity and complement each other.