Total Sharp Score Research Articles

Analysis of integrated radiographic data from two long-term, open-label extension studies of adalimumab for the treatment of rheumatoid arthritis.

A longitudinal integration approach evaluated all radiographic scores assessed over 10 years, rather than only completer data, from 2 studies of adalimumab (ADA) for rheumatoid arthritis (RA). The DE019 (methotrexate [MTX]-inadequate responders, longstanding RA) and PREMIER (MTX-naive, early RA) studies, respectively, had 1- or 2-year double-blind periods followed by 9- or 8-year open-label extensions (OLEs). Patients received ADA ± MTX in both OLEs. Radiographic progression was assessed using change from baseline in modified total Sharp score (ΔmTSS). A mixed-effects model was used post hoc to evaluate repeated measurements of different data campaigns and to estimate ΔmTSS through up to 10 years of treatment based on original randomization groups (placebo [PBO] + MTX or standard dose ADA + MTX). Data from patients with baseline and ≥1 postbaseline radiograph were included (n = 327 for DE019; n = 452 for PREMIER). Integrated and 10-year completer ΔmTSS progression curves differed slightly. In DE019, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 6.6 units (integrated model) and 6.2 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 0.9 units by integrated analysis and 0.7 units in completers. In PREMIER, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 11.2 units (integrated analysis) and 11.0 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 5.1 units (integrated analysis) and 4.0 units (completers). A higher radiographic progression rate was observed in patients who received delayed versus immediate ADA + MTX treatment. Longitudinal integrated analysis provided robust estimates of radiographic progression that only slightly differed from completers-only scores and confirmed the effects.

Clinical significance of soluble programmed death-1(sPD-1) in rheumatoid arthritis patients: Relation to disease activity and functional status

BackgroundProgrammed cell death-1 (PD-1) is an immunoreceptor that negatively regulates antigen receptor signaling and plays a critical role in the immunoregulation of autoimmune diseases. Aim of the workThis study aimed to measure the plasma and synovial fluid levels of soluble programmed death-1(sPD-1) in rheumatoid arthritis (RA) patients and to correlate them with the clinical and laboratory characteristics, disease activity, functional status and radiological severity. Patients and methodsWe measured sPD-1 in the plasma (n=60) and synovial fluid (SF) samples (n=24) from 60 RA patients and in the plasma from healthy control (n=30). In the patients, disease activity score using 28 joint counts (DAS28) and the health assessment questionnaire (HAQ) score were assessed; immunoglobulin-M rheumatoid factor (IgM-RF) titer, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer and C-reactive protein (CRP) levels were measured and total Sharp score calculated. ResultsIn RA patients both plasma and SF sPD-1 levels (1416.9±1037.9pg/ml and 1503.9±1129.48pg/ml respectively) were highly significantly increased compared to its plasma level in the healthy control (165±26.11pg/mL) (p<0.001). In RA patients, the plasma and SF levels of sPD-1 significantly correlated with DAS28 (r=0.52 and 0.58 respectively, p<0.05), HAQ scores (r=0.48 and 0.51 respectively, p<0.05) and anti-CCP titers (r=0.55 and 0.58 respectively, p<0.05). ConclusionsRheumatoid arthritis patients have significantly elevated plasma and synovial levels of sPD-1 that remarkably correlated with the DAS28 suggesting that it could be a useful marker to reflect RA disease activity. The considerable association of sPD-1 with autoantibodies production implies a possible role in the pathogenesis of RA.

Predictive factors related to the efficacy of golimumab in patients with rheumatoid arthritis.

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metallo-proteinase (MMP)-3, TNF-α, and IL−6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

Predictive value of bone destruction and duration of clinical remission for subclinical synovitis in rheumatoid arthritis patients

Objectives. Treatment for rheumatoid arthritis (RA) should aim to achieve full remission. The aim of this study was to investigate predictors of persistent subclinical synovitis and whether longer clinical remission is effective in reducing subclinical synovitis.Methods. Forty-four RA patients who achieved DAS28ESR clinical remission for at least 3 months were enrolled in this study and underwent ultrasound examination of 22 joints (bilateral proximal interphalangeal joints, metacarpophalangeal joints, and wrists); bilateral hand X-ray; and blood examination. The severity of synovial effusion, synovial hypertrophy, and blood flow were semi-quantitatively graded from 0 to 3 using gray-scale (GS) and power Doppler (PD) modes.Results. Among patients with DAS28ESR-defined clinical remission, 59.1% (26/44) demonstrated residual synovitis (≥ PD1) in at least one joint. Genant-modified total Sharp score (TSS) demonstrated the highest statistical difference between patients with and without residual subclinical synovitis (p = 0.0057), and full remission was only observed in patients with low TSS. A nonsignificant trend for decreased residual synovitis with longer sustained clinical remission was also observed (p = 0.724).Conclusion. Residual synovitis can persist during clinical remission, particularly in patients with progressive bone destruction. Early treatment and longer sustained clinical remission prior to bone destruction are critical for full remission.

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.

Which factors influence radiographic progression during treatment with tumor necrosis factor inhibitors in clinical practice? Results from 930 patients with rheumatoid arthritis in the nationwide Danish DANBIO registry.

To investigate baseline characteristics associated with radiographic progression and the effect of disease activity, drug, switching, and withdrawal on radiographic progression in tumor necrosis factor (TNF) inhibitor-naive patients with rheumatoid arthritis (RA) followed for about 2 years after anti-TNF initiation in clinical practice. DANBIO-registered patients with RA who had available radiographs (anti-TNF initiation and ∼2 yrs followup) were included. Radiographs were scored, blinded to chronology with the Sharp/van der Heijde method and linked with DANBIO data. Baseline characteristics were investigated with univariate regression and significant variables included in a multivariable logistic regression analysis with ± radiographic progression [Δ total Sharp score (TSS) > 0] as dependent variable. Effect of time-averaged C-reactive protein (CRP), 28-joint Disease Activity Score with CRP (DAS28-CRP), and treatment status at followup were investigated with univariate regression analysis. The study included 930 patients. They were 75% women, 79% positive for IgM-rheumatoid factor (IgM-RF), median age was 57 yrs (range 19-88), disease duration 9 yrs (1-59), DAS28-CRP 5.0 (1.4-7.8), TSS median 15 [3-45 interquartile range (IQR)] and mean 31 (SD 40). Patients started treatment with infliximab (59%), etanercept (18%), or adalimumab (23%). At followup (median 526 days, IQR 392-735), 61% were treated with the initial anti-TNF, 29% had switched TNF inhibitor, and 10% had withdrawn. Twenty-seven percent of patients had progressed radiographically. ΔTSS was median 0.0 [0.0-0.5 IQR/mean 0.6 (SD 2.4)] units/year. Higher TSS, older age, positive IgM-RF, and concomitant prednisolone at baseline were associated with radiographic progression. Time-averaged DAS28-CRP and time-averaged CRP, but not type of TNF inhibitor, were associated with radiographic progression. Patients who stopped/switched during followup progressed more than patients who continued treatment. High TSS, older age, IgM-RF positivity, and concomitant prednisolone were associated with radiographic progression during 2 years of followup of 930 anti-TNF-treated patients with RA in clinical practice. High disease activity and switching/stopping anti-TNF treatment were associated with radiographic progression.

Biologic-free remission of established rheumatoid arthritis after discontinuation of abatacept: a prospective, multicentre, observational study in Japan.

Objective. The aim of this study was to determine whether biologic-free remission of RA is possible with discontinuation of abatacept.Methods. Japanese RA patients in 28-joint DAS with CRP (DAS28-CRP) remission (<2.3) after >2 years of abatacept treatment in a phase II study and its long-term extension entered this 52 week, multicentre, non-blinded, prospective, observational study. At enrolment, the patients were offered the option to continue abatacept or not. The primary endpoint was the proportion of patients who remained biologic-free at 52 weeks after discontinuation. Clinical, functional and structural outcomes were compared between those who continued and those who discontinued abatacept.Results. Of 51 patients enrolled, 34 discontinued and 17 continued abatacept treatment. After 52 weeks, 22 of the 34 patients (64.7%) remained biologic-free. Compared with the continuation group, the discontinuation group had a similar remission rate (41.2% vs 64.7%, P = 0.144) although they had a significantly higher mean DAS28-CRP score at week 52 (2.9 vs 2.0, P = 0.012). The two groups were also similar with regard to mean HAQ Disability Index (HAQ-DI) score (0.6 for both, P = 0.920), mean change in total Sharp score (ΔTSS; 0.80 vs 0.32, P = 0.374) and proportion of patients in radiographic remission (ΔTSS ≤ 0.5) at the endpoint (64.3% vs 70.6%, P = 0.752). Those attaining DAS28-CRP < 2.3 or < 2.7 without abatacept at the endpoint had significantly lower HAQ-DI score and/or CRP at enrolment. Non-serious adverse events occurred in three patients who continued or resumed abatacept.Conclusion. Biologic-free remission of RA is possible in some patients after attaining clinical remission with abatacept. Lower baseline HAQ-DI or CRP may predict maintenance of remission or low disease activity after discontinuation of abatacept.Trial registration: UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ (UMIN000004137).

Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia® as Biological Intensive Treatment for RA (ORBIT) study

Objective. To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice.Methods. We performed a retrospective study of 137 RA patients who were treated with abatacept for 24 weeks between October 2010 and June 2011 at four rheumatology centers in Japan. Outcomes were compared between biologic-naïve and biologic-experienced patients. Disease activity was assessed using the Simplified Disease Activity Index (SDAI) and the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR).Results. The retention rate of abatacept at 24 weeks was 79.6%. SDAI (from 24.6 ± 12.5 to 12.9 ± 11.6) and DAS28-ESR (from 5.2 ± 1.4 to 3.9 ± 1.4) decreased significantly from baseline to Week 24 (both P < 0.001). Remission/low disease activity were achieved in 2.2%/11.2% (SDAI) and in 5.3%/2.3% (DAS28-ESR). The change in SDAI and the remission/low disease activity rates at Week 24 was greater in biologic-naïve patients than in biologic-experienced patients. Structural remission (van der Heijde-modified total Sharp score ≤ 0.5) was achieved by 63.4% of patients.Conclusions. The present results confirm that abatacept is effective in routine clinical practice and support its use as the first-line biologic agent in patients.

Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study

ObjectiveTo analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified...

Tofacitinib versus Methotrexate in Rheumatoid Arthritis

BackgroundMethotrexate is the most frequently used first-line antirheumatic drug. We report the findings of a phase 3 study of monotherapy with tofacitinib, an oral Janus kinase inhibitor, as compared with methotrexate monotherapy in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.MethodsWe randomly assigned 958 patients to receive 5 mg or 10 mg of tofacitinib twice daily or methotrexate at a dose that was incrementally increased to 20 mg per week over 8 weeks; 956 patients received a study drug. The coprimary end points at month 6 were the mean change from baseline in the van der Heijde modified total Sharp score (which ranges from 0 to 448, with higher scores indicating greater structural joint damage) and the proportion of patients with an American College of Rheumatology (ACR) 70 response (≥70% reduction in the number of both tender and swollen joints and ≥70% improvement in three of five other criteria: the patient's assessment of pain, level of disability, C-reactive protein level or erythrocyte sedimentation rate, global assessment of disease by the patient, and global assessment of disease by the physician).ResultsMean changes in the modified total Sharp score from baseline to month 6 were significantly smaller in the tofacitinib groups than in the methotrexate group, but changes were modest in all three groups (0.2 points in the 5-mg tofacitinib group and <0.1 point in the 10-mg tofacitinib group, as compared with 0.8 points in the methotrexate group [P<0.001 for both comparisons]). Among the patients receiving tofacitinib, 25.5% in the 5-mg group and 37.7% in the 10-mg group had an ACR 70 response at month 6, as compared with 12.0% of patients in the methotrexate group (P<0.001 for both comparisons). Herpes zoster developed in 31 of 770 patients who received tofacitinib (4.0%) and in 2 of 186 patients who received methotrexate (1.1%). Confirmed cases of cancer (including three cases of lymphoma) developed in 5 patients who received tofacitinib and in 1 patient who received methotrexate. Tofacitinib was associated with increases in creatinine levels and in low-density and high-density lipoprotein cholesterol levels.ConclusionsIn patients who had not previously received methotrexate or therapeutic doses of methotrexate, tofacitinib monotherapy was superior to methotrexate in reducing signs and symptoms of rheumatoid arthritis and inhibiting the progression of structural joint damage. The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start ClinicalTrials.gov number, NCT01039688.)

Methotrexate for treating rheumatoid arthritis.

Methotrexate for treating rheumatoid arthritis.

OP0034 Identification of Genetic Variants Associated with Response to Methotrexate in Patients with Early Rheumatoid Arthritis: Results from the Optima Study

BackgroundGenetic factors related to treatment response in rheumatoid arthritis (RA) have been described. International recommendations for the management of RA suggest initial therapy with synthetic DMARDs, with methotrexate (MTX) typically...

FRI0266 Health-Related Quality of Life of Patients with Rheumatoid Arthritis Achieving DAS28 Remission, Improvement in Physical Function and NO Radiographic Progression after Treatment with Intravenous Golimumab

ObjectivesTo evaluate “comprehensive remission” in patients with rheumatoid arthritis (RA) treated with intravenously administered golimumab (GLM) and the association with normalized health related quality of life (HRQOL).MethodsGO-FURTHER was a multicenter,...

SAT0214 Statistical Evalution of Joint Damage Prgression in Patients with Rheumatoid Arthritis Treated with Infliximab or Biosimilar Infliximab (CT-P13) Anti-TNF Therapy: A Role of Sensitivity Analysis for Missing Data Evaluating Similarity

BackgroundBiosimilar infliximab (CT-P13) was the first monoclonal antibody biosimilar of innovator infliximab (INX) approved by the European Medicines Agency. In the PLANETRA study (1), patients with rheumatoid arthritis received 3...

AB0260 Dynamic Serum Matrix Metalloproteinase-3 as A Diagnostic Biomarker of Erosive Disease and Radiographic Progression in Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis, resulting in joint destruction and disability. Matrix metalloproteinase (MMP) 3 plays essential role in the degradation of extracellular components...

FRI0267 A Prediction Model That Identifies Patients Most Likely to Benefit from First-Line Therapy with Adalimumab plus Methotrexate in Early Rheumatoid Arthritis

BackgroundIn early rheumatoid arthritis (RA), adalimumab (ADA) + methotrexate (MTX) as first-line treatment yields superior clinical and radiological outcomes versus MTX monotherapy but entails risk for overtreatment and high costs....

SAT0218 Validating Responsiveness and Discrimination of the Rheumatoid Arthritis Magnetic Resonance Imaging SCORE (RAMRIS) – A Meta-Analysis of Randomized Controlled Trials (RCTS) Identified in A Systematic Literature Review

BackgroundRadiographs (hands ± feet) measured with total Sharp scores (TSS) are considered the reference standard for quantifying structural damage in RA clinical trials. Magnetic resonance imaging (MRI) is increasingly utilized...

AB0218 Changes in ACPA during 24-Week Therapy with Tocilizumab (TCZ) for Rheumatoid Arthritis (RA) PREDICT Long-Term Progression of Articular Destruction: 2-Year Results of Extended Actor Study

BackgroundAnti-citrullinated protein antibodies (ACPA) aggravate inflammation, activate osteoclasts, and accelerate bone resorption in RA patients.1 We previously reported that a decrease in ACPA was observed during 52 weeks of TCZ...

THU0131 Long Term Results of Inhibition of Radiographic Joint Damage Progression in Small and Medium and Large Joints in Patients with Rheumatoid Arthritis Treated with Tofacitinib Monotherapy

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). There was a study concerned with the efficacy for inhibiting the progression of radiographic...

AB0258 Persistence of Extensive MRI Osteitis Associates RAPID Radiographic Progression with Predominant Loss of Joint SPACE Narrowing and Hand Grip in Patients with Rheumatoid Arthritis Inadequate Response to Methotrexate

BackgroundMagnetic resonance imaging (MRI) osteitis has been reported to be a strong independent predictor of radiographic joint damage (RJD) in rheumatoid arthritis (RA) (1). We reported continuation of MRI osteitis,...