Target Of Low Disease Activity Research Articles

Implementation of the Treat-to-Target Approach in Psoriatic Arthritis and Its Outcomes in Routine Clinical Practice.

Background Measuring disease activity in psoriatic arthritis using validated tools and treating to a target (T2T) is advocated. It improves quality of life and delays radiographic progression. In clinical practice, it guides therapy escalation to achieve better disease control. This study aimed to assess the real-life implementation of the T2T concept in daily clinical practice and the proportion of patients achieving the target of low disease activity or remission. Methodology In this study, a retrospective review of patients diagnosed with psoriatic arthritis having clinical visits from January 2020 to February 2023 was done. The proportion of patients in whom disease activity was monitored using the Disease Activity Index for Psoriatic Arthritis (DAPSA) 28 and Physician Global Assessment (PGA) and those achieving the target was calculated using SPSS version 21 (IBM Corp., Armonk, NY, USA). Results A total of 89 patients were included in the study after fulfilling the inclusion and exclusion criteria. Overall, 56.2% (50) of patients were males and 43.8% (39) were females, with a mean age of 43.5 ± 14.5 years, mean disease duration of 6.6 ± 3.8 years, and mean follow-up duration of 2.8 ± 1.6 years. Of the study population, 43.8% (39) had axial involvement, 23.6% (21) had dactylitis, and 12.4% (11) had enthesitis. Skin psoriasis was present in 84.3% (75), 11.2% (10) had a family history of psoriasis, 19.1% (17) had nail changes, 1.1% (1) had uveitis, and in 94.8% (73) of patients skin psoriasis presented before arthritis. Overall, 97.7% (85) of patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with the most common being methotrexate in 77%, followed by leflunomide in 8%. Further, 34.8% (31) were using biological DMARDs (bDMARDs), with the most common being tofacitinib (33.7%), infliximab (28.1%), and secukinumab (24.7%) being other choices. Overall, 21.1% (18) of patients experienced adverse events with csDMARDs and 3.2% (1) with biological DMARDs. DAPSA28 was recorded in 44.9% (40), Psoriasis Area and Severity Index in 16.8% (15), and PGA in 100% of patients. Target of low disease activity (LDA)/remission was achieved in 50.6% (45) patients, as assessed by PGA or DAPSA28 cutoff. The LDA/remission target was achieved in 51.2% of patients taking csDMARDs, and 74.2% in those who were on bDMARDs. Conclusions It is crucial to measure the disease activity using validated tools and treat the patient to target for achieving better disease control and improved quality of life. Despite the evidence that T2T improves outcomes, it is not widely practiced in routine clinical practice.

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.

Short-Term Efficacy and Safety of Subcutaneous Tocilizumab in Rheumatoid Arthritis Patients in Pakistan: A Real-World Experience

Objective: To determine the real-world efficacy and safety of subcutaneous Tocilizumab in patients with rheumatoid arthritis.
 Study Design: Case series.
 Place and Duration of Study: Department of Rheumatology, National Hospital and Medical Centre, Lahore Pakistan, from Aug 2019 to Dec 2020.
 Methodology: In this study, 33 patients receiving subcutaneous Tocilizumab 162 mg every two weeks as monotherapy or with conventional synthetic disease modifying anti-rheumatic drugs were followed per standard study protocol. Increasing or decreasing the dosing interval was allowed according to disease activity at the discretion of the treating rheumatologist. The primary outcome was patients achieving Low Disease Activity as per Clinical Disease Activity Index (>2.8-10.0) and Disease Activity Score-28(>2.6-3.2). The secondary outcome was a clinically meaningful improvement in Disease Activity Score -28 (reduction of ≥1.2 units in Disease Activity Score-28 score). Adverse events were recorded at each follow-up visit.
 Results: Of the 33 patients, 25(75.8%) were biologics-naive, 9(27.2%) patients achieved the target of Low Disease Activity as per Clinical Disease Activity Index (2.9-10.0) and 8(24.2%) patients achieved Low Disease Activity as per Disease Activity Score-28(2.7-3.2). At six months, the proportion of patients achieving clinically meaningful improvement (decrease ≥1.2) in Disease Activity Score -28 was 13(54.2%). Overall, 14(42.4%) patients developed adverse events and 3(9.1%) patients discontinued Tocilizumab owing to adverse events.
 Conclusion: Tocilizumab has been seen to be an effective biologic in only one-third of patients, and it was tolerated in twothirds of the patients.Keywords: Conventional synthetic disease modifying anti-rheumatic drugs, Efficacy, Rheumatoid arthritis, Safety, Subcutaneous tocilizumab.

OA39 Development of a Childhood Lupus Low Disease Activity State definition: recommendations from the International Childhood Lupus Treat-to-Target Task Force

Abstract Background/Aims International interest in development of treat-to-target (T2T) in both childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) is increasing. T2T could facilitate more effective and structured use of treatments, aggressively controlling disease activity, preventing organ damage, and improving health-related quality of life. The first step is the selection of an appropriate target. Remission is deemed the ultimate target, but may not be attainable by all. Low disease activity (LDA), based on the principle of “tolerable” disease activity on stable treatment, with low corticosteroid dosage, may be more appropriate for some patients. The aim of this study was to derive a consensus-based cSLE appropriate definition of LDA, building upon existing aSLE definitions to improve applicability to cSLE, whilst maintaining sufficient unity to ensure that future T2T studies including adolescents and adults together are possible. Methods The International cSLE T2T Task Force, including 18 specialists from paediatric rheumatology/nephrology, and adult rheumatology undertook a series of Delphi surveys, exploring views on aSLE LDA targets. Two virtual consensus meetings were held, utilising a modified nominal group technique to debate, modify, and vote upon topics underpinning the cSLE LDA target and its criteria. Agreement of > 80% was considered consensus. Results The task force agreed that the LDA target should encompass cSLE as a whole and be based upon the aSLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it more applicable to cSLE (cLLDAS, all 100% agreement). A conceptual definition of cLLDAS was defined: ‘A state, which if sustained, is associated with a low likelihood of adverse outcome (considering disease activity, damage, and medication toxicity)’ (100% agreement). Five cLLDAS criteria were agreed, as detailed within Table 1. The final cLLDAS definition was endorsed by the Paediatric Rheumatology European Society (PReS) Executive Council and PReS cSLE Working Party Chair, on behalf of the Society. Conclusion A cSLE, age-appropriate definition of cLLDAS has been generated, preserving sufficient unity with the aSLE LLDAS definition to encourage life-course research. The development and validation of targets has been a key enabler for T2T trials, therefore this initiative represents a significant step forward for cSLE. Disclosure E.M.D. Smith: None. A. Aggarwal: None. J. Ainsworth: None. E. Al-Abadi: None. T. Avcin: None. L. Bortey: None. J. Burnham: None. C. Ciurtin: None. C.M. Hedrich: None. S. Kamphuis: None. D. Levy: None. L. Lewandowski: None. N. Maxwell: None. E. Morand: None. S. Ozen: None. C. Pain: None. A. Ravelli: None. C. Saad Magalhaes: None. C. Pilkington: None. D. Schonenberg: None. C. Scott: None. K. Tullus: None. M.W. Beresford: None.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity

Objectives Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. Methods Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). Results There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. Conclusion Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Clusterin serum levels are elevated in patients with early rheumatoid arthritis and predict disease activity and treatment response

Clusterin (CLU) is a molecular chaperone that participates in a variety of biological processes. Recent studies indicate its possible involvement in the development of bone erosions and autoimmunity. The aim of this study was to investigate its serum concentrations in patients with early rheumatoid arthritis (RA) and to explore their potential relationship with disease activity and treatment response. Serum levels of CLU were measured in 52 patients before and 3 months after the initiation of treatment and in 52 healthy individuals. CLU levels at baseline were significantly increased in patients with early RA compared with healthy subjects (p < 0.0001). After 3 months of treatment, the levels of CLU decreased and reached concentrations comparable to those in controls. Even though there was no relationship between CLU levels and disease activity at baseline, CLU levels positively correlated with disease activity at months 3, 6 and 12 after treatment initiation. Using ROC analysis, lower CLU baseline levels predicted achieving the therapeutic target of low disease activity and remission at months 3, 6 and 12. In summary, we found increased serum concentrations of clusterin in treatment-naïve patients with early rheumatoid arthritis, and we suggest clusterin as a predictive biomarker of disease activity and treatment response.

P172 Quality of life improvements in patients with PsA who achieve remission or low disease activity targets: results from two clinical trials of ixekizumab at three years of treatment

P172 Quality of life improvements in patients with PsA who achieve remission or low disease activity targets: results from two clinical trials of ixekizumab at three years of treatment

Early non-response to certolizumab pegol in rheumatoid arthritis predicts failure to achieve low disease activity at 1 year: data from a prospective observational study

ObjectiveTo evaluate the performance of clinical criteria for predicting late treatment failure in patients with early non-response to certolizumab pegol (CZP).MethodsA protocol-specified analysis of interim data from ECLAIR, a 3-year...

Treating juvenile idiopathic arthritis to target: recommendations of an international task force

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations...

Connective tissue diseases: New low disease activity target defined in SLE.

Connective tissue diseases: New low disease activity target defined in SLE.

Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update

ObjectiveA systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations.MethodsTwo SLRs...

Treat-to-target approach in daily clinical practice in Pakistani patients with early Rheumatoid Arthritis.

To determine the frequency of patients with early Rheumatoid Arthritis (RA) achieving disease remission and/or low disease activity after 6 months of treatment with conventional Disease Modifying Anti-Rheumatic Drugs (DMARDs) by using treat-to-target approach in routine clinical practice. Descriptive study. Division of Rheumatology, Fatima Memorial Hospital (FMH), College of Medicine and Dentistry, Lahore, from March 2011 to February 2012. Patients with early RA defined as disease duration ² 1 year were enrolled by purposive sampling, diagnosed as per American College of Rheumatology (ACR) 1987 criteria. Treat-to-target approach was defined as per European League Against Rheumatism (EULAR) 2010 guidelines for treatment of RA with conventional DMARDs. Outcome measures of remission and low disease activity were defined as per DAS 28 score criteria. Patient response to treatment was also determined by EULAR response criteria. Out of 67 patients, 50 patients completed the 6 months study period, rest were lost to follow-up. All patients were started on Methotrexate and mean weekly dose at 6 months was 18.9 ± 3.8 mg. Remission was achieved in 17 (34%) and target of low disease activity was achieved in 29 (58%) of patients. EULAR good response was seen in 28 (56%), moderate response in 21 (42%) and no response to treatment in 1 (2%). By applying treat-to-target approach in early RA, achievement of clinical remission or low disease activity with conventional DMARDs is a realistic goal in routine practice.

Personalized medicine in rheumatoid arthritis: is the glass half full or half empty?

The care of patients with rheumatoid arthritis (RA) has been revolutionized since the 1990s. Strict monitoring and disease control based on measurement of signs and symptoms towards a target of low disease activity have improved outcome of patients enormously. As a result of treatment strategies based upon individualized measurement of disease activity, the clinical view of RA has changed from a destructive autoimmune disease (with a median joint damage of >10 Sharp units per year) to a condition in which significant damage can be prevented in the majority of patients. Moreover, a large number of targeted therapies (tumour necrosis factor, IL6, CD80/CD86 and CD20 inhibitors) have become available to better treat the underlying disease process. However, identification of the underlying pathways that drive the disease process in an individual patient has been relatively unsuccessful, implying that no predictive factors have been identified to guide the choice of a specific treatment. Distinct subsets of RA patients have been identified, based on the presence or absence of anticitrullinated protein antibodies (ACPAs). These two subsets are associated with different environmental and genetic risk factors, histology and disease outcome (a more destructive disease course with more persistent joint inflammation is observed when ACPAs are present). Therefore, it is recommended that treatment should be guided towards a more consistently low level of disease activity in the presence of ACPAs than in the absence of the antibodies.

Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE).

The aim of this study was to evaluate structural damage and physical disability in patients with elderly-onset RA (EORA) who were treated in clinical practice with a therapeutic strategy targeting low disease activity (LDA). Data from 151 MTX-naive patients (mean age 74.9 years) with EORA from a prospective, monocentric registry were analysed. Treatment was adjusted every 3 months targeting LDA [28-joint DAS using ESR (DAS28-ESR) <3.2]. Treatment was initiated with non-biologic DMARDs (nbDMARDs), followed by TNF inhibitors (TNFis) or tocilizumab. The primary outcome was change from week 0 to week 52 in the modified total Sharp score (ΔmTSS). Secondary outcomes were derived from the HAQ Disability Index (HAQ-DI) and DAS28 at week 52. Predictors of clinically relevant radiographic progression [CRRP; ΔmTSS/year more than the smallest detectable change (2.1 points)] were examined using multivariate logistic regression models. Adherence to the treat-to-target strategy was observed in 83.4% of the 151 patients at week 24 and in 75.5% at week 52. At week 52, 67.6% of the patients were receiving a nbDMARD alone, 31.0% a TNFi with or without MTX and 1.4% tocilizumab. At week 52, structural remission (ΔmTSS/yr ≤0.5) was achieved in 49.7% of the patients, functional remission (HAQ-DI ≤0.5) in 63.4% and LDA in 51.0%. Clinical responses at weeks 12 and 24 were significant independent predictors of CRRP. Cumulative disease activity during the first 12 weeks predicted CRRP with a C-statistic of 0.888. Achieving structural remission, functional remission and LDA in clinical practice in EORA patients are realistic goals. Our results indicate significant benefits for a therapeutic strategy targeting LDA for EORA patients in clinical practice.

Psoriasis and psoriatic arthritis in African-American patients--the need to measure disease burden.

Gaps in knowledge exist regarding the clinical characteristics of psoriatic disease in ethnic minority patients. We evaluated validated clinical disease measures of psoriasis and psoriatic arthritis in African-American and Caucasian patients. Adult outpatients with confirmed diagnoses of psoriasis and psoriatic arthritis and seen at four urban academic institutions were eligible for evaluation. Validated patient and physician-reported disease outcome parameters, quality of life measures of psoriasis and psoriatic arthritis, and frequencies of systemic immunosuppressive therapies and patient comorbidities were documented. Psoriatic arthritis was less frequent in African-Americans compared to Caucasians (30 vs. 64.5%, respectively, p < 0.001); however, African-Americans had more severe skin involvement [Psoriasis Area and Severity Index 8.4 (10.0) vs. Caucasians 5.5 (6.4), p = 0.06], with greater psychological impact and impaired quality of life. Use of biologic therapies was greater in Caucasian patients (46.2 vs. 13.3%in African-Americans, p < 0.0001); yet, only one in four patients of the study cohort achieved minimal disease activity. Comorbidity was not associated with frequency of immunosuppressive drug use. In order to achieve a target of low disease activity and to reduce ethnic disparities in the care of psoriatic disease, the routine application of measures of disease status is needed.

FRI0025 Compliance with Treat to Target Recommendations & Its Impact on Control of Rheumatoid Arthritis – Interim Results of A UK Multicentre Audit

BackgroundBased on a strong evidence base that pre-determined treatment targets & tight control improve outcomes, 2010 recommendations on treating to target aim to improve rheumatoid arthritis (RA) management [1].ObjectivesThis prospective...

AB0377 Clinical, Functional, and Structural Consequences of Targeting Low Disease Activity Rather than Remission in Early and Established Rheumatoid Arthritis Using Methotrexate or Methotrexate plus Adalimumab

BackgroundRheumatoid arthritis (RA) treat to target (tgt) recommendations advocate clinical remission (REM) as the tgt; targeting low disease activity (LDA) is an alternative for patients (pts) who cannot attain REM....

SAT0589-HPR Body Mass Index and Its Relationship to Disease Activity in Early Rheumatoid Arthritis

BackgroundObesity rates in Canada have increased 3% (to 25%) over the past 8 years. Obese patients develop more severe forms of many diseases and have more comorbidities develop over time....

OP0270-HPR Should A Successful Early Inflammatory Arthritis Clinic Also Address Cardiac Risk?

BackgroundRA patients have higher cardiovascular disease (CVD) risk. There is a 60% increase in the risk of death from cardiovascular causes compared with the general population and, survival rates for...

Barriers to Optimal Disease Control for Rheumatoid Arthritis Patients With Moderate and High Disease Activity

To evaluate barriers that prevent rheumatoid arthritis (RA) patients from achieving Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) scores within the current recommended levels for low disease activity (LDA) or clinical remission (DAS28-ESR score <3.2). Using an electronic medical record program, clinical data for RA patients treated in Optimising Patient Outcomes in Australian Rheumatology clinics, with a recorded DAS28-ESR score, were collected at one point in time. The data included demographics, medications, disease measures, and the rheumatologist's opinion of the main barriers preventing improvement to the recommended DAS28 score. Of the 4,037 patients with a recorded DAS28-ESR score, 304 patients (7.5%) had high disease activity (HDA) and 1,211 patients (30%) had moderate disease activity (MDA). For 584 HDA or MDA patients, the barriers to disease control (BTCs) were recorded by the rheumatologist when there was no adjustment to disease-modifying antirheumatic drug (DMARD) therapy. The recorded BTCs were irreversible joint damage (19.7%), patient-driven preference (14.7%), noninflammatory musculoskeletal pain (9.2%), insufficient time to assess the effect of recently initiated DMARDs (9.2%), safety concerns (7.5%), comorbidities (6.5%), resistant disease (6.3%), and other less common reasons. These patients received DMARDs (97.4%), including biologic agents (34.1%), methotrexate (74.8%), and oral corticosteroids (41.8%). This study identified clinical situations in which rheumatologists elected to continue RA patients with MDA or HDA on DMARD therapy without adjustment to achieve clinical remission or an LDA target of a DAS28-ESR score <3.2.