Total Genant-modified Sharp Score Research Articles

AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis.

Aim Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). Methods In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). Results 52 subjects were enrolled (80% female, mean (SD) age 57 (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. Conclusion Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. Trial registration This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703).

Relationship between roentgenographic joint destruction in the hands and functional disorders among patients with rheumatoid arthritis

Objectives: Although a relationship between joint destruction and functional disorders seems apparent in patients with rheumatoid arthritis (RA), it has not been well proven in the literature. The aims of this study were to clarify the relationship between roentgenographic joint destruction in the hands and functional disorders in patients with RA, and to explore the appropriate assessment measures for functional disorders.Methods: Cross-sectional data of the Genant-modified Total Sharp Score (Genant-mTSS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Disabilities of the Arm, Shoulder, and Hand (DASH), and Michigan Hand Outcomes Questionnaire (MHQ) were collected from 50 consecutive RA patients and analyzed.Results: HAQ-DI, DASH, and MHQ had close correlations with Genant-mTSS, with correlation coefficients of 0.69, 0.71, and −0.70, respectively, among patients with low disease activity (DAS28 < 3.2). A floor effect was observed in HAQ-DI, but neither floor nor ceiling effects were observed in DASH and MHQ. Both DASH and MHQ were strongly correlated with HAQ-DI, with correlation coefficients of 0.87 and 0.73, respectively.Conclusions: Functional disorders had significant relationships with roentgenographic joint destruction in the hands among RA patients with low disease activity. As assessment measures of functional disorders, DASH and MHQ had no floor or ceiling effects, being different from HAQ-DI.

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.

Rituximab for rheumatoid arthrits treatment: a systematic review

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti-TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases. MethodsWe conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti-TNF agents before, and to relate outcome with RF and anti-CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta-analysis. ResultsWe included six RCTs comparing rituximab 1000mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti-TNF treatment failure patients - ACR20/50/70 and EULAR response. We observed lower changes in Total Genant-modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF-36, FACIT-T and HAQ-DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti-CCP seropositive patients achieved ACR20 than RF/anti-CP negative patients in rituximab group. ConclusionAvailable data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti-TNF treatment failure patients. RF and anti-CCP seam to influence treatment results, but this inference needs further research.

SAT0103 Lithe: Tocilizumab (TCZ) Inhibits Radiographic Progression and Improves Physical Function in Patients (PTS) With Rheumatoid Arthritis (RA) at 5 Years With Maintenance of Clinical Efficacy Over Time

BackgroundLITHE was a 2-y, randomised, double-blind, placebo-controlled study of TCZ in pts with moderate to severe RA who were inadequate responders to methotrexate (MTX) with an additional 3 y of...

THU0244 Drug Therapy in Undifferentiated Arthritis: A Systematic Literature Review

BackgroundPart of the cases with undifferentiated arthritis (UA), an inflammatory oligo-arthritis without definitive diagnosis, may be a first manifestation of rheumatoid arthritis (RA). As early treatment in RA results in...

Tocilizumab Inhibits Structural Joint Damage and Improves Physical Function in Patients with Rheumatoid Arthritis and Inadequate Responses to Methotrexate: LITHE Study 2-year Results

To assess radiographic progression, physical function, clinical disease activity, and safety in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX) and who were treated with tocilizumab-MTX or MTX during Year 2 of a 2-year study. During Year 1, patients were randomized to placebo-MTX, 4 mg/kg tocilizumab-MTX, or 8 mg/kg tocilizumab-MTX. During Year 2, patients continued the initial double-blind treatment or switched to open-label 8 mg/kg tocilizumab-MTX. Co-primary endpoints at Week 104 were mean change from baseline in Genant-modified Total Sharp Score (GmTSS) and adjusted mean area under the curve (AUC) for change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI). Signs and symptoms of RA and safety were also evaluated. At Week 104, mean change from baseline in GmTSS was significantly lower for patients initially randomized to tocilizumab-MTX 4 mg/kg (0.58; p = 0.0025) or 8 mg/kg (0.37; p < 0.0001) than for patients initially randomized to placebo-MTX (1.96). Adjusted mean AUC of change from baseline in HAQ-DI was also significantly lower in patients initially randomized to tocilizumab-MTX 4 mg/kg (-287.5; p < 0.0001) or 8 mg/kg (-320.8; p < 0.0001) than in patients initially randomized to placebo-MTX (-139.4). Signs and symptoms of RA were maintained or showed improvement. No new safety signals were noted. Compared with placebo-MTX, tocilizumab-MTX significantly inhibited structural joint damage and improved physical function in patients with RA who previously had inadequate response to MTX. An extension of this study is continuing and will provide additional longterm efficacy and safety data. National Clinical Trials registry NCT00106535.

Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction

BackgroundTreatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease...

Sustained inhibition of progressive joint damage with rituximab plus methotrexate in early active rheumatoid arthritis: 2-year results from the randomised controlled trial IMAGE

BackgroundIn the IMAGEstudy, rituximab plus methotrexate (MTX) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis.ObjectiveThe aim of this study was...

Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: Results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structu

To assess the efficacy and safety of tocilizumab plus methotrexate (MTX) versus MTX alone in preventing structural joint damage and improving physical function and disease activity in patients with moderate-to-severe rheumatoid arthritis and inadequate responses to MTX. A total of 1,196 patients were enrolled in a 2-year, randomized, double-blind, placebo-controlled trial. Patients received tocilizumab (8 mg/kg or 4 mg/kg) or placebo every 4 weeks plus MTX. Rescue treatment was available from week 16. Results from year 1 are presented. Mean change in the total Genant-modified Sharp score was 0.29 and 0.34 with tocilizumab 8 mg/kg plus MTX and 4 mg/kg plus MTX, respectively, versus 1.13 with placebo plus MTX (P < 0.0001 for both comparisons). Analysis of variance of the area under the curve for change from baseline in the disability index of the Health Assessment Questionnaire showed greater decreases with tocilizumab 8 mg/kg and 4 mg/kg (-144.1 and -128.4 units, respectively) than with placebo (-58.1 units; P < 0.0001 for both comparisons). Proportions of patients with American College of Rheumatology 20%, 50%, and 70% improvement and with Disease Activity Score in 28 joints remission were higher in those receiving 8 mg/kg tocilizumab than in those receiving placebo (P < 0.0001 for all comparisons). The safety profile of tocilizumab was consistent with the profiles in previous studies. Infections were the most common adverse and serious adverse events. The findings of this study show that tocilizumab plus MTX results in greater inhibition of joint damage and improvement in physical function than does MTX alone. Tocilizumab has a well-characterized safety profile.

Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond (<20% improvement in swollen and tender joint count; SJC and TJC) then stepwise rescue therapy could begin at week 16. Patients with ≥ 70% improvement in SJC and TJC could continue the blinded therapy at the end of year 1 to week 104. For all other patients, open-label TCZ8 was initiated at week 52. Change from baseline in Genant-modified total Sharp score (GmTSS) and physical function (AUC of change from baseline in HAQ-DI) were the primary 2-year end points. Linear extrapolation (GmTSS) or standardization (change in HAQ-DI) was used for missing data. The impact of 2 years of treatment was examined by assessing efficacy end points over time for patients randomized to TCZ8, with the last observation carried forward for SJC and TJC in patients who received rescue therapy or withdrew. Results: The intention to treat population consisted of 398 TCZ8, 399 TCZ4 and 393 CON patients. At 2 years, exposure rates in patient-years (PY) were 1320.0, 521.9 and 284.8 in TCZ8, TCZ4 and CON patients, respectively. At year 2, patients in the TCZ8 group had 81% less radiographic progression vs CON patients (based on linear extrapolation of mean change in GmTSS). Significantly more TCZ8 patients had no radiographic progression vs CON patients (P ≤ 0.0001). AUC of change from baseline in HAQ-DI showed significant improvement in physical function in TCZ4 and in TCZ8 vs CON patients (P ≤ 0.0025). In patients initially randomized to TCZ8, a low disease activity score (LDAS; DAS28 < 3.2) was seen in > 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honoraria.