Definition Of Remission Research Articles

Similar levels of disease activity and remission rates in patients with psoriatic arthritis and rheumatoid arthritis—results from the Finnish quality register

ObjectivesTo compare the current disease activity and remission rates, and their regional variation in patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in Finland.MethodsData of patients’ most recent visit in 1/2020–9/2021 were extracted from the Finnish Rheumatology Quality Register. Measures for disease activity and remission included joint counts, DAS28, cDAPSA, CDAI, the Boolean definition, and physician assessment. Regression analyses were applied, adjusted for age and sex.ResultsData of 3598 patients with PsA (51% female, mean age 54 years) and 13,913 patients with RA (72% female, 74% ACPA-positive, mean age 62 years) were included. The median (IQR) DAS28 was 1.9 (1.4, 2.6) in PsA and 2.0 (1.6, 2.7) in RA (p = 0.94); for cDAPSA, the median (IQR) values were 7.7 (3.1, 14) in PsA and 7.7 (3.3, 14) in RA (p < 0.001). In all regions in both diseases, the median DAS28 was ≤ 2.6 and the median cDAPSA < 13. Remission rates included DAS28 < 2.6 in 73% in PsA and 69% in RA (p = 0.17) and Boolean remission in 17% in PsA and 15% in RA (p < 0.001). By other definitions of remission, the rates ranged between 30% and 46%. Methotrexate was currently used by 49% in PsA and 57% in RA (p < 0.001). Self-administered bDMARDs were currently used by 37% in PsA and 21% in RA (p < 0.001).ConclusionThe overall disease activity was low and similar in patients with PsA and RA across the country. Remission rates varied between 15 and 73%, depending on the definition but were similar in PsA and RA.Key Points• The disease activity and clinical picture was similar between patients with PsA and RA, in a cross-sectional setting in 1.2020–9.2021.• A significant majority of patients with PsA had low disease activity or were in remission according to cDAPSA. Majority of patients with RA were in remission according to DAS28.• Patients with PsA and RA used methotrexate similarly. The utilization of bDMARDs was more prevalent in patients with PsA.

Persistent esophageal changes after histologic remission in eosinophilic esophagitis

BackgroundEosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood and therefore chronic EoE-directed therapy is required to prevent long-term sequelae. ObjectiveWe investigated if with EoE patients in histologic remission have persistent dysregulation of esophageal gene expression. MethodsEsophageal biopsies from pediatric (n=51) and adult (n=52) subjects with EoE in histopathologic remission (<15 eos/HPF) and control (n=48 pediatric, n=167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE Diagnostic Panel (EDP), a set of 94 esophageal transcripts differentially expressed in active EoE. ResultsDefining remission as <15 eosinophils/HPF, we identified 511 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (FDR < 0.05). Using the stringent definition of remission (0 eos/HPF), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (FDR ≤ .05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the Endoscopic Reference Score (Spearman r= 0.35, p= 0.011), specifically correlating with the rings EREFS subscore (r= 0.53, p=0.004). ConclusionWe have identified persistent EoE-associated esophageal gene expression in patients with deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.

Clinical Trial Design in Ulcerative Colitis: Interpreting Evolving Endpoints Based on Post Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1.

The 12-point total Mayo score including a Physician's Global Assessment (PGA) of disease activity has been used to assess outcomes in clinical trials for ulcerative colitis (UC). In 2016, the US Food and Drug Administration (FDA) issued guidance advising the removal of the PGA in future trials. We examined how endpoints in UC trials have evolved and conducted a post hoc analysis of the GEMINI 1 and VISIBLE 1 trials to understand how the use of a 9-point modified Mayo score, excluding PGA, compares with the total Mayo score. Endpoint definitions of clinical remission in phase 3 trials were extracted from published literature and ClinicalTrials.gov. The difference (%Δ) between the proportions of patients in GEMINI 1 and VISIBLE 1 achieving clinical remission with vedolizumab versus placebo at week 52 was measured according to 4 endpoint definitions. Trials completed up to the end of 2019 used the total Mayo score to assess clinical remission. Most trials that were completed or estimated to be completed by June 2020 or later used modified Mayo scores. Post hoc analysis revealed decreasing endpoint stringency was associated with increasing %Δ values. The modified Mayo score definition most like the definition recommended by the FDA produced %Δ values like those reported using the total Mayo score in GEMINI 1 and VISIBLE 1. Endpoint definitions for UC clinical trials have evolved following FDA guidance. The efficacy of vedolizumab, measured using modified Mayo scoring, was comparable to values reported using the total Mayo score.

Should Airway Hyper-Responsiveness Be Included in the Definition of Clinical Remission With Biologic Therapy in Severe Asthma

Airway hyper-responsiveness (AHR) is a tenet of the persistent asthma phenotype along with reversible airway obstruction and type 2 (T2) inflammation. Indirect acting challenges such as mannitol are more closely related to the underlying T2 inflammatory process as compared with direct challenges. In this review article, we summarise the current literature and explore the future role of mannitol AHR in clinical remission with biologics.

Nex-T TM Cluster of Differentiation 19 (CD19) Chimeric Antigen Receptor (CAR) T-Cell Therapy BMS-986353 (CC-97540): Comparative Analysis of Baseline Patient Data from Trials in Systemic Lupus Erythematosus (SLE) and Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL) Related to Manufacturability and Potential Safety

Introduction: CAR T-cell therapy is currently being evaluated in non-oncologic autoimmune diseases (Mougiakakos D et al. N Engl J Med 2021; Müller F et al. Lancet 2023). In a cohort of patients (pts) with SLE, CD19 CAR T-cell therapy resulted in B-cell depletion and treatment-free, durable remission per Definitions of Remission In SLE (DORIS), suggesting that CD19 CAR T therapy may be feasible, well-tolerated, and effective for patients with SLE (Mackensen A et al. Nat Med 2022). Baseline traits associated with greater manufacturing success and lower toxicity profiles for CAR T have been identified in hematologic oncology (Mashadi-Hossein A et al. J Clin Oncol 2023; Rytlewski J et al. J Clin Oncol 2022) including age, bone marrow function, inflammatory state, and tumor burden. Here, we compared baseline traits in pts with active SLE versus R/R LBCL to predict the potential manufacturing success and toxicity profile for the ongoing phase 1 study to evaluate the investigational NEX-T TM CAR T-cell product BMS-986353 (CC-97540) in pts with severe, refractory SLE (NCT05869955). Methods: This post hoc analysis compared 42 quantitative baseline traits between pts with active SLE from PAISLEY (NCT03252587; Morand E et al. Arthritis Rheumatol 2023) and pts with R/R LBCL from TRANSCEND (NCT02631044; Abramson J et al. Lancet 2020). Baseline traits associated with improved manufacturing success and/or lower toxicity profile for CAR T in hematologic oncology were compared (Mashadi-Hossein A et al. J Clin Oncol 2023; Rytlewski J et al. J Clin Oncol 2022). A Wilcoxon rank-sum test was used to compare pt cohorts. Data are median (95% confidence interval). Results: This analysis included 363 pts with SLE and 256 pts with R/R LBCL. Of 42 baseline traits compared, 36 had nominal P values ≤ 0.05; 33 of those were ≤ 0.001. High baseline absolute lymphocyte count (ALC), platelets (PLT), and hemoglobin (Hgb) were previously associated with both improved manufacturing success and a lower toxicity profile for CAR T; pts with SLE had higher ALC, PLT, and Hgb vs R/R LBCL (ALC: 1.15 10 9/L [1.07-1.20 10 9/L] vs 0.10 10 9/L [0.10-0.13 10 9/L], P &amp;lt; 0.001, Figure 1A; PLT: 239 10 9/L [232-249 10 9/L] vs 144 10 9/L [129-154 10 9/L], P &amp;lt; 0.001; Hgb: 128 g/L [126-130 g/L] vs 98.0 g/L [95.0-100.0 g/L], P &amp;lt; 0.001), which is predictive of both improved manufacturing success and potentially lower toxicity. Young baseline age and high red blood cell (RBC) counts were previously associated with improved manufacturing success, and pts with SLE were younger and had higher RBC counts vs R/R LBCL (age: 40 years [38-41 years] vs 63 years [61-64 years], P &amp;lt; 0.001; RBCs: 4.30 10 12/L [4.20-4.40 10 12/L] vs 3.13 10 12/L [3.05-3.20 10 12/L], P &amp;lt; 0.001), predicting improved CAR T manufacturing success. Baseline traits reflecting tumor burden and/or bone marrow involvement that have been previously associated with higher toxicity, such as high C reactive protein (CRP; Figure 1B), high lactate dehydrogenase (LDH), and low hematocrit (Hct), were different between pts with SLE vs R/R LBCL (CRP: 1.92 mg/L [1.60-2.48 mg/L] vs 20.0 mg/L [15.5-31.8 mg/L], P &amp;lt; 0.001; LDH: 184 U/L [179-191 U/L] vs 282 U/L [251-317 U/L], P &amp;lt; 0.001; Hct: 39.0% [39.0-40.0%] vs 29.6% [28.7-30.5%], P &amp;lt; 0.001), and predict potentially lower toxicity. Conclusions: Comparison of baseline pt data from trials in SLE vs R/R LBCL suggests that pts with SLE have traits that predict improved manufacturing success and lower rates/severity of common CAR T-associated toxicities such as cytokine release syndrome (CRS) and neurological events. A key difference between cohorts is the potential for high tumor burden in R/R LBCL which has been previously associated with CAR T toxicity. Our results show marked differences between cohorts for tumor burden surrogate measures (CRP, LDH, Hct), bone marrow function, inflammatory state, and age which we hypothesize may potentially lead to improved CAR T manufacturing success and lower risk of CRS and/or neurological events for patients with autoimmune disorders vs R/R LBCL. Further research is needed to understand if CAR T-cell therapy may provide a promising treatment option for pts with SLE and other autoimmune conditions. The ongoing phase 1, multicenter, open-label study will evaluate the safety, feasibility, and preliminary efficacy of BMS-986353 (CC-97540) in patients with severe, refractory SLE. Study support: Bristol Myers Squibb

Importance of FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) in Staging and Response Assessment of Hairy Cell Leukemia (HCL)

Alessandro Mancini and Luca De Carolis are Co-first authors. Nicodemo Baffa, Brunangelo Falini and Enrico Tiacci are Co-last authors. INTRODUCTION HCL is an indolent BRAF-mutated leukemia usually presenting with cytopenias, splenomegaly, little or no lymphadenopathy, heavy bone marrow (BM) infiltration and few circulating leukemic cells. Imaging exams for staging include abdominal echography and computed tomography (CT), while the role of PET is largely unknown. METHODS 84 patients (pts) with relapsed/refractory HCL participating to our clinical trials of BRAF inhibitor-based therapies prospectively underwent PET/CT pre- and post-treatment, in addition to usual examinations for response assessment. Since FDG uptake is normally higher in liver than spleen, BM and lymph nodes, uptake in the latter tissues was considered abnormal if equal to or higher than the liver. Splenomegaly was defined by a longest spleen diameter &amp;gt;13 cm on PET/CT. The standard definition of complete remission (CR) in HCL just requires no palpable splenomegaly on physical examination, in addition to resolution of cytopenias as well as no hairy cells visible in the blood smear and the BM biopsy by non-immunological stains. RESULTS Pre-therapy, 58/77 (75%) non-splenectomized pts showed abnormal splenic FDG uptake (maximal standardized uptake value/SUVmax: median 4.8, vs 3.9 for the liver), which was always diffuse without focal lesions. Conversely, focal splenic uptake is not infrequent in splenic marginal zone lymphoma (18%, 7/39 pts - Abdom Radiol 2018;43:2721; vs of 0/58 HCL pts, p=0.0003), which may aid in the differential diagnosis with this HCL-mimicker. Moreover, 14/58 (24%) HCL pts. with a PET+ spleen did not have splenomegaly, and splenic uptake returned to normal in 10/11 evaluable cases (91%) achieving at least a partial response post-therapy, which suggests leukemic spleen involvement even without splenomegaly. Abnormal diffuse BM uptake was observed in 41/82 evaluable pts (50%; median SUVmax 5, vs 3.4 for the liver). In these cases, leukemic involvement in the BM biopsy was greater (median 80%) than in the other 41 pts (median 65%; p-value &amp;lt;0.01), pointing to HCL infiltration as the cause of abnormal BM uptake rather than to reactive hyperplasia of non-involved BM. Post-therapy, pathologic spleen uptake normalized in 46/51 evaluable pts (90%), and their CR rate was higher (32/46 pts, 70%) than in the other 5 pts remaining PET+ (1/5, 20%; p=0.047). Among the 46 PET- cases, 31 (67%) were not splenomegalic while 15 (33%) had residual splenomegaly (up to 17 cm; Fig. 1A); interestingly, within PET- cases relapse-free survival (RFS) was similar not only in conventionally defined CR cases with (n=8) vs without (n=24) residual non-palpable splenomegaly (p=0.84 after a median follow-up of 19 months), but also when the 6 cases meeting all conventional CR criteria except for still palpable splenomegaly were added to the 8 CR pts with residual non-palpable splenomegaly (p=0.7 after a median follow-up of 20.5 months - Fig. 1B). These findings suggest that metabolic status reflects splenic HCL involvement more reliably than spleen size or palpability, a concept that could improve the current definition of CR in HCL. Abnormal BM uptake resolved after treatment in 34/37 evaluable pts (92%), and their CR rate was again higher (23/34, 68%) than in the other 3 pts remaining PET+ (0/3; p=0.047). Leukemic infiltration of the BM biopsy was lower in the 34 PET- vs the 3 PET+ pts (median 5% vs 70%-80%, respectively; p=0.0004), indicating that BM abnormal uptake reflects HCL infiltration load rather than reactive BM hyperplasia post-therapy. Finally, abnormal lymph node uptake was observed pre-therapy in 9/84 (11%) pts (median SUVmax 7.1, vs 3.4 for the liver) and normalized after treatment in 7/8 evaluable pts (88%), including one case with residual lymph node enlargement (2.2 cm); all these 7 pts had achieved a CR while the remaining pt had no response to therapy. CONCLUSIONS PET is potentially useful in the differential diagnosis with splenic marginal zone lymphoma and may aid in the clinical management of HCL pts by detecting metabolic involvement of the main disease sites even in the absence of organomegaly. Importantly, PET signal tracks with response to therapy even in case of persistent organomegaly, which may lead to refine the definition of CR in HCL.

Harmonizing Medicine and Surgery in the Pursuit of Boolean Remission: A Rheumatological Magnum Opus.

Rheumatic diseases encompass a diverse group of musculoskeletal conditions that often lead to inflammation, pain, and significant limitations in patients' lives. While traditional treatment approaches have primarily centered on medications to control symptoms, recent developments have introduced the concept of Boolean remission. Boolean remission offers a comprehensive evaluation of disease activity by considering clinical, biochemical, and patient-reported outcomes. This narrative review explores the multifaceted landscape of Boolean remission in the context of rheumatic diseases, with a focus on rheumatoid arthritis (RA), as it remains a substantial clinical challenge. The review outlines the definition, criteria, historical context, and development of Boolean remission, shedding light on its emergence as a more patient-centered and stringent treatment goal. The role of pharmacological interventions, including immunomodulators and biologics, in achieving Boolean remission is discussed, emphasizing the significance of treatment protocols that encompass regular monitoring, medication adjustment, shared decision-making, and patient education. Surgical interventions, such as joint replacements and synovectomies, complement medication-based strategies when joint damage becomes severe, with adherence to surgical protocols ensuring sustained Boolean remission. The integration of medicine and surgery through integrated care models and interdisciplinary teams is examined as a critical aspect of optimizing patient outcomes. Boolean remission's broader impact on healthcare policies and clinical trial endpoints is explored, underscoring its growing significance in rheumatic disease management. The review concludes by looking towardthe future, where emerging technologies, biomarkers, and personalized medicine approaches hold promise in refining Boolean remission criteria and making it a more attainable and impactful treatment goal. Policy implications suggest the integration of Boolean remission into healthcare quality metrics, incentivizing healthcare providers to prioritize this rigorous standard of care. Boolean remission represents a pivotal shift in the holistic and patient-centered management of rheumatic diseases, offering hope for improved patient outcomes and enhanced quality of life in this challenging clinical landscape.

‘Symptom-free’ when inflammatory bowel disease is in remission: Expectations raised by online resources

ObjectivesUp to 60% of patients with inflammatory bowel disease (IBD) experience symptoms when in remission. Qualitative research suggests patients seldom feel they receive adequate explanations for these. This study explores how, and how often, ongoing symptoms during remission are represented on readily searchable patient websites. MethodsBing, Google, and Yahoo were searched for websites providing medical information about IBD. Thematic analysis was used to inductively explore themes around symptoms during quiescent IBD, followed by deductive content analysis to quantify core themes. ResultsResults indicated that remission is commonly defined as “few or no symptoms” and that there is limited information available on symptoms during remission. 55.6% of IBD websites provided a definition of remission based on symptom control only, while 44.4% also incorporated inflammatory control. The few websites that mentioned that symptoms may continue during remission (21.7%) related these to IBS. ConclusionsCurrent website information is predominantly biomedical and fails to adequately explain how symptoms may persist during remission and how IBS and IBD may be linked. Practice ImplicationsLack of explanatory models of symptoms in remission may lead to distress and increase anxiety about symptoms. Clearer explanations of these symptoms are needed.

The effect of systemic lupus erythematosus (SLE) Disease Activity Score and SLE Disease Activity Index 2000-based remission states in patients with SLE on damage accrual.

This study aimed to compare the effect of the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) with the SLE Disease Activity Index 2000 (SLEDAI-2K) remission state on damage accrual. This study classified SLE patients from the Lupus Clinic of the Royal Thai Army (LUCRA) cohort based on the SLE-DAS index, or Boolean-based, and SLEDAI-2K (Doria) remission state. Regression analysis models were constructed to identify predictors of the Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) during follow-up. There were 197 patients identified; 97 patients met at least one definition of remission state, and 100 patients were in the non-remission group at enrollment. Of 97 patients, 97 achieved the SLE-DAS index-based definition, 74 achieved the SLE-DAS Boolean-based definition, and 55 achieved the Doria definition. The mean ± SD of follow-up was 4.77 ± 0.6 years. The changes in SDI over time were non-significantly lower in patients who met any definition of remission compared with those who did not. Multivariate analysis revealed that predictive factors for increased SDI were age and baseline SDI ≥ 1. SLE-DAS index, Boolean, and Doria-based definitions of remission at enrollment had no significant risk reduction on SDI compared with the non-remission group (HR 0.7, 95% CI 0.37-1.32, p = .27; HR 0.73, 95% CI 0.37-1.44, p = .37; HR 0.8, 95% CI 0.39-1.65, p = .55, respectively). Patients with SLE who achieved remission status according to the SLE-DAS index or SLEDAI-2K definitions did not show any significant difference in damage accrual compared to those who were not in remission.

Clinical remission in severe asthma with biologic therapy: an analysis from the UK Severe Asthma Registry.

Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline. 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.

Targeting DORIS Remission and LLDAS in SLE: A Review.

Remission is the established therapeutic goal for patients with systemic lupus erythematosus (SLE) and is currently defined by the widely adopted Definition Of Remission In SLE (DORIS) criteria. Attainment of remission is rare in the clinical setting, thus an alternative, pragmatic treatment target of low disease activity, as defined by the Lupus Low Disease Activity State (LLDAS), provides a less stringent and more attainable treatment goal for a wider proportion of patients compared with DORIS remission. Randomized controlled trials and real-world analyses have confirmed the positive clinical benefits of achieving either DORIS remission or LLDAS. The treat-to-target (T2T) approach utilizes practical clinical targets to proactively tailor individual treatment regimens. Studies in other chronic inflammatory diseases using the T2T approach demonstrated significantly improved clinical outcomes and quality-of-life measures compared with established standard of care. However, such trials have not yet been performed in patients with SLE. Here we review the evolution of DORIS remission and LLDAS definitions and the evidence supporting the positive clinical outcomes following DORIS remission or LLDAS attainment, before discussing considerations for implementation of these outcome measures as potential T2T objectives. Adoption of DORIS remission and LLDAS treatment goals may result in favorable patient outcomes compared with established standard of care for patients with SLE.

Impact of low disease activity, remission, and complete remission on flares following tapering of corticosteroids and immunosuppressive therapy in patients with systemic lupus erythematous: a multinational cohort study.

Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission. This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission. Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare. Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months. AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

Care pathway analysis and evidence gaps in adult-onset Still's disease: interviews with experts from the UK, France, Italy, and Germany.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology. Published AOSD data are limited, and clinical guidelines were lacking until recently. Managing AOSD remains largely empirical with uncertainties and high variability about the optimal care pathway. Therefore, we used a qualitative approach to collect clinical judgments from the UK, Italy, France and Germany to inform the development of an agreed care pathway. Our work aimed to decrease the uncertainty associated with clinical practice, inform future research in AOSD, and help identify standardized definitions and outcomes in this population. Semi-structured interviews and thematic analysis were conducted. Eleven clinicians were interviewed between May and July 2022: four were based in Italy, three in the UK, two in France, and two in Germany. In this work, we identified the structure of the typical care pathway for AOSD patients, which can be used to inform future economic models in AOSD. The general structure of the pathway was similar across countries. Non-steroidal anti-inflammatory drugs are prescribed during the diagnostic workup while an additive approach is commonly used in confirmed cases: corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, then biologic disease-modifying antirheumatic drugs (bDMARDs) (dose increased before switching). For severe presentations, more aggressive approaches with higher doses and early use of bDMARDs are used. The main elements of variation among countries and clinicians were the criteria used for diagnosis; order of bDMARDs and preferential treatments for articular and systemic patients; and tests for patient monitoring. There is also a lack of standardized outcome measures making comparisons and evidence synthesis challenging. We identified important evidence gaps for clinical practice, e.g., reliable tests or scores predictive of disease progression and treatment outcome, and recommendations for research, e.g., reporting of compliance rates and use of the Yamaguchi criteria for clinical study inclusion. Consensus is needed around the use of the Systemic score in clinical practice and the clinical utility of this score. A standardized definition of remission is also required in AOSD, and further research should look to identify and validate the specific laboratory markers to be considered when assessing remission.

Consensus of an American College of Allergy, Asthma, and Immunology, American Academy of Allergy, Asthma, and Immunology, and American Thoracic Society workgroup on definition of clinical remission in asthma on treatment

Consensus of an American College of Allergy, Asthma, and Immunology, American Academy of Allergy, Asthma, and Immunology, and American Thoracic Society workgroup on definition of clinical remission in asthma on treatment

Defining the physician global assessment threshold equivalent to remission in patients with systemic lupus erythematosus.

The optimal threshold of the physician global assessment (PGA) for remission in SLE has never been evaluated systematically. The aim of this study was to assess the ideal PGA threshold associated with physician remission and to investigate its impact on remission rates in our lupus cohort. In this monocentric cross-sectional study, patients with SLE were evaluated for physician remission by asking the treating physicians whether they considered their patient to be in remission, regardless of objective remission criteria. Furthermore, two objective remission definitions were applied: (i) DORIS (Definition Of Remission In Systemic Lupus Erythematosus) remission using a PGA of <2 (0-10) (corresponding to <0.5 on a visual analogue scale 0-3 used in DORIS); and (ii) DORIS remission with omission of PGA (modDORIS). A receiver operating characteristic analysis and regression analyses were performed to assess the ideal PGA threshold and factors influencing PGA. Of the 233 patients included, 126 patients (54.0%) were in physician remission, 42.5% in DORIS remission and 67.0% in modDORIS remission. A PGA of <2 [numeric rating scale (NRS) 0-10] had the highest sensitivity (79%) and specificity (81%) for physician remission and modDORIS (area under the curve 0.85 and 0.69). PGA of patients fulfilling any of the remission definitions was associated with pain and hypocomplementemia. Damage was numerically higher in patients in modDORIS only; no association between PGA and damage was found in regression analysis. Using a PGA threshold of <2 (0-10), corresponding to <0.6 (0-3), resulted in best prediction of physician remission. PGA levels seem to be influenced by pain and complement levels but not disease damage.

Management of adult-onset Still's disease: evidence- and consensus-based recommendations by experts.

Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline.

Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study

ObjectivesWe aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA).MethodsWe used data from the ReFlaP, an international multi-centre cohort...

Remission, response, retention and persistence to treatment with disease-modifying agents in patients with rheumatoid arthritis: a study of harmonised Swedish, Danish and Norwegian cohorts

ObjectivePrecision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study...

Health-related quality of life, remission and low lupus disease activity state in patients with systemic lupus erythematosus.

To measure the association between SLE remission and scores of patients-reported outcome (PRO) measures. We performed a prospective cohort study of SLE patients with a 2-year follow-up, using Lupus Patient-Reported Outcome (LupusPRO), Lupus Quality of Life (LupusQoL), Systemic Lupus Erythematosus Quality of Life (SLEQOL) and 36-item Short Form (SF-36) questionnaires. Remission was defined as remission off treatment (ROFT) and remission on treatment (RONT) according to the definitions of remission in SLE consensus. Mixed models accounting for repeated measures were used to compare groups as follow: ROFT and RONT vs no remission and lupus low disease activity state (LLDAS) vs no LLDAS. A total of 1478 medical visits and 2547 PRO questionnaires were collected during the follow-up from the 336 recruited patients. A between-group difference in PRO scores reaching at least 5 points on a 0-100 scale was obtained in the following domains: lupus symptoms (LLDAS: +5 points on the 0-100 scale, RONT: +9, ROFT: +5), lupus medication (LLDAS: +5, RONT: +8, ROFT: +9), pain vitality (LLDAS: +6, RONT: +9, ROFT: +6) of LupusPRO; role emotional (LLDAS: +5, RONT: +8), role physical (RONT: +7 and ROFT: +7), bodily pain (RONT: +6), mental health (RONT: +5) and social functioning (RONT: +6) of SF-36. In contrast, a between-group difference reaching at least 5 points was not achieved for any of the LupusQoL and SLEQOL domains. RONT, ROFT and LLDAS were associated with significant and clinically relevant higher QoL in most PRO domains of the LupusPRO (disease specific) and SF-36 (generic) questionnaires, but not with LupusQoL and SLEQOL disease-specific questionnaires.

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality

BackgroundEsketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.MethodsPost hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined.ResultsThe median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up.ConclusionTreatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality.Trial registrationClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).