Criteria For Low Disease Activity Research Articles

Comparative Efficacy of Advanced Therapies in the Treatment of Radiographic Axial Spondyloarthritis or Ankylosing Spondylitis as Evaluated by the ASDAS Low Disease Activity Criteria.

With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations. A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed. Among the TNFi-naïve population, the estimated ASDAS LDA rate between week12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies. Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers.

Efficacy and safety of the type I interferon receptor inhibitor anifrolumab in patients with systemic lupus erythematosus (results of a 6-month study)

Objective: to evaluate the efficacy and safety of the type I interferon (IFN) receptor inhibitor anifrolumab (AFM, Safnelo®) in patients with systemic lupus erythematosus (SLE) in real-life clinical practice over an observation period of 6 months.Material and methods. The prospective 6-month study included 21 patients with SLE fulfilling the 2012 SLICC criteria, predominantly women (n=17,81%), median age – 31 [27; 46] years, disease duration – 9 [6.0; 11.0] years. Standard laboratory values and immunological markers of SLE were examined in all patients. The SLEDAI-2K index was used to determine the activity of SLE, and the severity of the mucocutaneous syndrome was assessed using the Cutaneous Lupus Disease Area and Severity Index (CLASI) index. Organ damage was assessed using the SLICC/ACR Damage Index (DI). After 6 months, the achievement of low activity was assessed according to the Lupus Low Disease Activity State (LLDAS) indexResults and discussion. At the time of inclusion in the study, the mean SLEDAI-2K activity index for the group was 8 [6.0; 10.0] points, the median CLASI index – 8.6±8.2 points, 81% of patients had skin and mucosal lesions, 66% had non-erosive polyarthritis, and high immunological activity was observed in all cases. Various irreversible organ damage was observed in 86 of patients. The average DI was 2.2±1.5 points. At the start of AFM therapy, all patients received glucocorticoids (GCs) at a mean dose of 10.7±5.6 mg/day, 52% of patients received a dose above 10 mg/day, 76% of patients continued to take hydroxychloroquine, and 33% of patients took immunosuppressants. Significant positive dynamics were observed with AFM therapy. The average CLASI index for the group after 3 months of treatment was 1.2±4.1 points, after 6 months – 0.3±1.2 points (p<0.0001). The SLEDAI-2K index fell significantly in the group on average from 8 [6.0; 10.0] to 2 [2.0; 4.0] points from the 3rd month of treatment (p<0.0001) and remained at the same level after 6 months. At month 6 of treatment, 13 (62%) of 21 patients met the LLDAS criteria for low disease activity. After the 3rd month of treatment, a significant decrease in antibodies against dsDNA was observed, which persisted for 6 months after the start of treatment. In the group as a whole, there were no significant changes in complement fractions values during the observation period. There was no increase in irreversible organ damage (DI – mean 2.2±1.5 points). The mean daily dose of GCs was significantly reduced from 10.7±5.6 mg/day to 7.5±4.0 mg/day (p<0.01) by the 3rd month and to 5.2±2.1 (p<0.001) by the 6th month of treatment. No infusion reactions were observed in any case. Adverse events occurred in 9 (42%) out of 21 patients, mainly herpes infections of varying severity, mainly after the 1st to 3rd infusions. In one case, severe herpes zoster was observed, so the drug was discontinued.Conclusion. At a dose of 300 mg intravenously monthly AFM is a highly effective drug with a relatively good safety profile in patients with active SLE in whom autoantibodies are present and who do not respond adequately to standard therapy.

PReS-endorsed international childhood lupus T2T task force definition of childhood lupus low disease activity state (cLLDAS)

ObjectiveTo achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials. MethodsThe International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria. ResultsThe Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0–3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics. ConclusionsA cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.

Determinants of Discordance Between Criteria for Inactive Disease and Low Disease Activity in Juvenile Idiopathic Arthritis.

To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Criteria for ID were met by 28.6-41.1% of patients with oligoarthritis and by 24.0-33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8-62.4% of patients with oligoarthritis and by 44.6-50.4% of patients with polyarthritis. There was a 57.9-62.3% overlap between criteria for ID and a 67.9-85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7-15.5%, 10.0-12.3%, and 10.8-17.3%, respectively). We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

OP0120 DURATION OF CLINICAL EFFICACY FOLLOWING TREATMENT WITH VIB4920 IN SUBJECTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS

Background:VIB4920 binds CD40 ligand and functionally neutralizes its engagement with CD401. We reported results through Day 85 of a Phase 1b, randomized, double-blind, placebo-controlled study (NCT02780388) in subjects with moderate to severe rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) or other disease modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor (TNF)-inhibitors1. We showed that at the end of the 12-week treatment period (Day 85), subjects treated with 1000 or 1500 mg VIB4920 (once every 2 weeks) had a clinically meaningful and statistically significant greater reduction in disease activity compared to placebo.Objectives:To assess the duration of clinical efficacy following the last dose of VIB4920 in subjects with moderate to severe RA.Methods:Subjects in the Phase 1b study (Ph1b) continued to have monthly safety and efficacy assessments between Days 85 and 169, the end of a 12-week follow-up. To estimate the subsequent duration of meaningful clinical improvement, we conducted an observational one-visit study (OS) (EudraCT 2019-002351-42) with the primary endpoint of time from last dose of VIB4920 to start of a new DMARD or biologic therapy or increase in dose of DMARD that was ongoing at Day 169 (ie, rescue therapy).Results:At Day 169 of the Ph1b (3 months after the last dose), clinical responses achieved at Day 85 were maintained in the 1000 and 1500 mg cohorts (Figure). Of 24 subjects, 16 (6/12 treated with 1000 mg and 10/12 with 1500 mg) participated in the OS. The median (range) time from Day 169 (last visit) in the Ph1b to the OS was 21.8 (21.2 to 23.1) months in the 1000 mg group and 33.7 (32.3 to 34.8) months in the 1500 mg group. All subjects had taken DMARDs (primarily methotrexate [MTX]) for at least part of this time (Table). Rescue therapy was started in 1/6 (16.7%) subject in the 1000 mg group and 3/10 (30.0%) subjects in the 1500 mg group (Table); median time to rescue could not be estimated due to the limited number of rescues. Two subjects were on no DMARDs at the OS. All subjects, except for 1 in the 1000 mg group, who was rescued with adalimumab, and 2 in the 1500 mg group (no rescue), had active disease (DAS28-CRP ≥ 2.6) at the OS. The median DAS28-CRP at the OS was higher than at Day 169 of the Ph1b but lower than at the Ph1b baseline visit (Table). Two subjects who received 1500 mg and met DAS28-CRP criteria for low disease activity (< 3.2) at Day 169 also met these criteria at the OS without receiving any rescue therapy after a median of nearly 37 months after last treatment. Results from the Patient and Physician Global Assessment VAS showed trends similar to the DAS28-CRP.Conclusion:Blocking CD40L with VIB4920 led to prolonged clinical benefit in patients with RA when added to stable background DMARD therapy. The exact duration of benefit could not be defined in this study, but most patients did not require rescue therapy during a prolonged follow-up period, and some patients maintained low disease activity or discontinued DMARDs, suggesting a possible long-term benefit of VIB4920. Interpretation of these data is limited because the OS did not include placebo-treated subjects from the Ph1b. The duration of clinical response needs to be confirmed in prospective, double-blind, placebo-controlled studies.

A Proposal to Standardize Low Disease Activity Criteria in Rheumatoid Arthritis Based on the Outcome Measures in Rheumatology Minimal Disease Activity Definition.

ObjectiveWe aimed to standardize the definition of low disease activity in rheumatoid arthritis (RA) using the Outcome Measures in Rheumatology (OMERACT) group's proposed definition of minimal disease activity.MethodBased on a nationwide RA database, we proposed new Boolean low disease activity criteria using OMERACT's core set definition of minimal disease activity that requires the fulfillment of at least five of the following seven core set measures: a pain score of 2 or less, a swollen joint count (SJC28) of 1 or fewer, a tender joint count of 1 or fewer, a Health Assessment Questionnaire score of 0.5 or less, a Physician's Global Assessment score of 1.5 or less, a Patient's Global Assessment score of 2 or less, and an erythrocyte sedimentation rate (ESR) of 20 mm/h or less. Using receiver operating characteristic analysis, we determined the cutoffs for the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Routine Assessment of Patient Index Data 3 (RAPID3), and the Disease Activity Score in 28 joints (DAS28)–ESR.ResultsOf 8298 patients, 56.2% met the proposed Boolean low disease activity criteria. We determined an SDAI score of 5.5 or less and a CDAI score of 5 or less to be the new cutoffs, and we chose a DAS28 of 2.85 or less (the original cutoff for DAS‐based minimal disease activity) and a RAPID3 score of 6 or less (the original cutoff for RAPID3‐based low disease activity) with or without a swollen joint count (SJC) (SJC of 2 or fewer) as the cutoffs for DAS28 and RAPID3. The agreement between the new cutoffs for DAS28 of 2.85 or less vs. CDAI score of 5 or less, CDAI score of 5 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), and DAS28 of 2.85 or less vs. RAPID3 score of 6 or less (with SJC of 2 or fewer), was 0.619, 0.612 (0.702), and 0.474 (0.531), respectively.Conclusion OMERACT's minimal disease activity definition may be used to standardize the criteria for low disease activity.

Lupus Low Disease Activity State Associated with Lower Fatigue

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations including fatigue. Previous studies aimed at proving the relationship between fatigue and SLE disease activity showed conflicting results. In 2015, Asia Pacific Lupus Collaboration (APLC) developed low disease activity criteria, named Lupus Low Disease Activity State (LLDAS). Patients who spend more time in LLDAS have significantly lower morbidity. This study aimed to evaluate the association between disease activity based on LLDAS and fatigue. 
 Methods: This is a analytical cross-sectional study. Subjects were SLE patients at rheumatology clinic in Dr. Hasan Sadikin Hospital, Bandung during June-January 2018. Subjects were evaluated based on LLDAS criteria and divided into 2 groups: LLDAS and non-LLDAS. Fatigue status of the subjects was assessed with Fatigue Severity Scale (FSS).
 Results: A hundred and thirty-three subjects were included in this study, divided into 63 subjects in LLDAS group and 60 subjects in non-LLDAS group. Nineteen subjects (30.2%) in LLDAS group had fatigue and 39 subjects (65%) in non-LLDAS had fatigue. There was a significant association between LLDAS and fatigue (p< 0.001). Nonetheless, fatigue level in LLDAS group was still high since disease activity was not the only factor related to fatigue. Fatigue may be a distinct clinical manifestation of neuropsychiatric lupus and may be independent of lupus disease activity
 Conclusions: There was a significant association between LLDAS and fatigue showed by lower fatigue level was found in the LLDAS group than in the non-LLDAS group.
 
 Keywords: Systemic lupus erythematosus, disease activity, Lupus Low Disease Activity State, fatigue

Histologic and Transcriptional Evidence of Subclinical Synovial Inflammation in Patients With Rheumatoid Arthritis in Clinical Remission.

Patients with rheumatoid arthritis (RA) in clinical remission may have subclinical synovial inflammation. This study was undertaken to determine the proportion of patients with RA in remission or with low disease activity at the time of arthroplasty who had histologic or transcriptional evidence of synovitis, and to identify clinical features that distinguished patients as having subclinical synovitis. We compared Disease Activity Score in 28 joints (DAS28) to synovial histologic features in 135 patients with RA undergoing arthroplasty. We also compared DAS28 scores to RNA-Seq data in a subset of 35 patients. Fourteen percent of patients met DAS28 criteria for clinical remission (DAS28 <2.6), and another 15% met criteria for low disease activity (DAS28 <3.2). Histologic analysis of synovium revealed synovitis in 27% and 31% of samples from patients in remission and patients with low disease activity, respectively. Patients with low disease activity and synovitis also exhibited increased C-reactive protein (CRP) (P = 0.0006) and increased anti-cyclic citrullinated peptide (anti-CCP) antibody levels (P = 0.03) compared to patients without synovitis. Compared to patients with a "low inflammatory synovium" subtype, 183 genes were differentially expressed in the synovium of patients with subclinical synovitis. The majority of these genes (86%) were also differentially expressed in the synovium of patients with clinically active disease (DAS28 ≥3.2). Thirty-one percent of patients with low clinical disease activity exhibited histologic evidence of subclinical synovitis, which was associated with increased CRP and anti-CCP levels. Our findings suggest that synovial gene expression signatures of clinical synovitis are present in patients with subclinical synovitis.

Defining Low Disease Activity in Systemic Lupus Erythematosus.

To define and identify a group of systemic lupus erythematosus patients with low disease activity (LDA) and to examine whether LDA is similar to patients in remission and different from a high disease activity group (HDA) in short-term outcomes. The LDA group was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) <3, including only 1 clinical manifestation of rash, alopecia, mucosal ulcers, pleurisy, pericarditis, fever, thrombocytopenia, or leukopenia. The patients could be taking antimalarials. Remission was defined as no clinical manifestation from taking antimalarials alone, and the HDA group was defined as SLEDAI-2K >6. The time frame for inclusion in each group was at least 1 year. Of 620 patients with active disease who were seen between 1970 and 2015, 80 patients (12.9%) fulfilled the criteria for LDA, 191 (30.8%) for remission, and 349 (56.3%) for HDA. The LDA patients with and without positive serology results were similar at baseline and with prior disease characteristics. After 2 years of followup, the LDA and remission groups were similar in their adjusted mean SLEDAI-2K score, organ involvement, The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score, mortality, and therapies. After 2 and 4 years of followup, the HDA group had a higher adjusted mean SLEDAI-2K score, more major organ involvement, a higher SDI score, higher mortality, and more therapy compared to the combined LDA/remission groups. LDA and remission groups had similar short-term outcomes, and both had better outcomes and prognosis than the HDA group. LDA may be used as an outcome measure in therapeutic trials or in treat-to-target regimens.

FRI0128 Less than 5% of ethnic minority rheumatoid arthritis (RA) patients meet inclusion criteria for randomized controlled clinical trials (RCT).

BackgroundRCT are the gold standard for therapeutic efficacy, yet many studies indicate most patients seen in routine clinical care do not meet inclusion criteria.1 Apart from cultural challenges to the...

FRI0189 Glucocorticoid discontinuation before biologic anti-rheumatic drug withdrawal is important in maintaining biologic-free success

ObjectivesTo assess real-life practice patterns of biologic discontinuation, including tocilizumab, for good response and factors associated with retreatment, we conducted a research on the Cohort of Arthritis, Biologic Users at...