THU0072 A Novel Dose Reduction Therapy Using Biological Disease-Modifying Anti-Rheumatic Drugs To Target Matrix Metalloproteinase 3 Normalization Together with A Simplified Disease Activity Index ≤3.3 Yields Effects Non-Inferior To Standard Care in Rheumatoid Arthritis with Regards Maintaining Remission

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 204.3-205
Author(s):  
Y. Urata ◽  
S. Abe ◽  
B. Devers ◽  
Y. Nakamura ◽  
H. Takemoto ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Dose Reduction ◽  
Standard Care ◽  
Activity Index ◽  
Disease Activity Index ◽  
Matrix Metalloproteinase 3 ◽  
Target Matrix ◽  
Disease Modifying

scholarly journals Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis

2019 ◽  
Vol 78 (12) ◽  
pp. 1609-1615 ◽  
Author(s):  
Daniel Aletaha ◽  
Jen-fue Maa ◽  
Su Chen ◽  
Sung-Hwan Park ◽  
Dave Nicholls ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Activity Index ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Response To Therapy ◽  
Joint Disease ◽  
Adalimumab Therapy ◽  
Disease Modifying

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses.ResultsIn the larger study (N=207), a greater number of prior DMARDs (>2 vs 0–1) was associated with smaller improvements in DAS28(CRP) (–1.8 vs –2.2), SDAI (–22.1 vs –26.9) and HAQ-DI (–0.43 vs –0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings.ConclusionsNumber of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.

Biomarkers in Remission According to Different Criteria in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 42 (11) ◽  
pp. 2066-2070 ◽  
Author(s):  
Sibel Yilmaz-Oner ◽  
Gulsen Ozen ◽  
Meryem Can ◽  
Pamir Atagunduz ◽  
Haner Direskeneli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Type I Collagen ◽  
Activity Index ◽  
Disease Activity Index ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Type I ◽  
Matrix Metalloproteinase 3 ◽  
Das28 Remission

Objective.Remission is the primary aim in the treatment of patients with rheumatoid arthritis (RA). In this study, we aimed to evaluate biomarker profiles of patients in remission by different criteria and compare these profiles with controls.Methods.Serum levels of calprotectin, interleukin 6 (IL-6), type II collagen helical peptide, C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3), resistin, and leptin were measured by ELISA in 80 patients. The patients were in Disease Activity Score at 28 joints with erythrocyte sedimentation rate (DAS28-ESR) remission, and had these characteristics: female/male 54/26, mean age 51.4 ± 12.1 years, mean disease duration 11.4 ± 8.1 years, rheumatoid factor positivity 68.7% (n = 55), anticyclic citrullinated peptide positivity 60.7% (n = 48). These patients were also evaluated for the American College of Rheumatology/European League Against Rheumatism (Boolean) and Simple Disease Activity Index (SDAI) remissions. Additionally, 80 age-, sex-, and comorbidity-matched individuals without rheumatic diseases were included in the study as controls.Results.At recruitment of 80 patients in DAS28 remission, 33 patients (41.2%) were found in Boolean remission and 39 patients (48.7%) were in SDAI remission. Serum MMP-3, ICTP, resistin, and IL-6 levels of the 80 patients in DAS28 remission were statistically significantly higher than the controls. Patients in Boolean and SDAI remissions had significantly higher serum ICTP, resistin, and IL-6 levels in comparison with the controls.Conclusion.The 3 commonly used remission criteria of RA are almost similar with regard to patients’ biomarker levels. Biomarker profiles of patients may provide complementary information to clinical evaluation of remission and may help to determine the patients under the risk of progression.

scholarly journals Serum Matrix Metalloproteinase-3 in Comparison with Acute Phase Proteins as a Marker of Disease Activity and Radiographic Damage in Early Rheumatoid Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Mahmood M. T. M. Ally ◽  
Bridget Hodkinson ◽  
Pieter W. A. Meyer ◽  
Eustasius Musenge ◽  
Mohammed Tikly ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinase ◽  
Disease Activity ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Activity Index ◽  
Acute Phase Reactants ◽  
Matrix Metalloproteinase 3 ◽  
Early Ra ◽  
Potential Biomarker

Matrix metalloproteinase-3 (MMP-3) is involved in the immunopathogenesis of rheumatoid arthritis (RA), but little is known about its relationship to genetic susceptibility and biomarkers of disease activity, especially acute phase reactants in early RA. MMP-3 was measured by ELISA in serum samples of 128 disease-modifying, drug-naïve patients and analysed in relation to shared epitope genotype, a range of circulating chemokines/cytokines, acute phase reactants, autoantibodies, cartilage oligomeric protein (COMP), and the simplified disease activity index (SDAI). MMP-3 was elevated >1.86 ng/ml in 56.25% of patients (P<0.0001), correlated with several biomarkers, notably IL-8, IL-6, IFNγ, VEGF and COMP (rvalues = 0.22–0.33,P<0.014–0.0001) and with CRP and SAA levels (r=0.40and 0.41, resp.,P<0.0000) and SDAI (r=0.29,P<0.0001), but not with erosions or nodulosis. However, the correlations of CRP and SAA with SDAI were stronger (respective values of 0.63 and 0.54,P<0.001for both). COMP correlated with smoking, RF, and MMP-3. MMP-3 is significantly associated with disease activity, inflammatory mediators and cartilage breakdown, making it a potential biomarker of disease severity, but seemingly less useful than CRP and SAA as a biomarker of disease activity in early RA.

scholarly journals The Aftermath of Tapering Tocilizumab After Achieving Treatment Target In Patients With Rheumatoid Arthritis: A Nationwide Cohort Study

2021 ◽  
Author(s):  
Jun Won Park ◽  
Min Jung Kim ◽  
Hyoun-Ah Kim ◽  
Jin Hyun Kim ◽  
Eun Bong Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Standard Dose ◽  
Tumor Necrosis Factor Inhibitor ◽  
Disease Activity Index ◽  
Estimating Equation ◽  
Low Disease Activity ◽  
Significant Difference ◽  
Disease Modifying

Abstract Background: Although recent guidelines recommend that tapering of biologic disease-modifying anti-rheumatic drugs (bDMARDs) can be considered in patients with rheumatoid arthritis (RA), there has been little evidence supporting the strategy during the non-tumor necrosis factor inhibitor treatment. This study aims to investigate the effectiveness and safety of tapering tocilizumab (TCZ) dose in patients with RA who attain low disease activity (LDA) after TCZ therapy in a nationwide cohort.Methods: Data were collected from a nationwide cohort of patients with RA receiving biologic disease-modifying anti-rheumatic drugs in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index-low disease activity (CDAI)-LDA (CDAI ≤ 10) after 1 year of treatment. We performed longitudinal analysis considering clinical data measured at all 1-year intervals for the included patients using the generalized estimating equation. A total of 575 intervals were classified into two groups according to their dose quotient (DQ) of TCZ (tapering group vs. standard-dose group). The main outcome was maintaining CDAI-LDA in the following 1-year interval.Results: Tapering TCZ dose strategy was used in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5) %. Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed that the tapering group was associated with more frequent failure to sustain CDAI-LDA (adjusted OR [95% CI]: 0.57 [0.33–0.99]), which subsequently led to impaired functional status. The likelihood of achieving DAS28-deep remission (DAS28-ESR<1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46–0.99]). CDAI remission was achieved in only 69 (12.0%) of the total intervals, with no significant difference in the proportion of intervals achieving the target between the two groups. Incidence of adverse events was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group. Conclusions: Tapering TCZ dose after achieving LDA increases the risk of losing LDA without a significant merit in safety.

Comparative Effectiveness of Nonbiologic versus Biologic Disease-modifying Antirheumatic Drugs for Rheumatoid Arthritis

2013 ◽  
Vol 40 (2) ◽  
pp. 127-136 ◽  
Author(s):  
ESI MORGAN DEWITT ◽  
YANHONG LI ◽  
JEFFREY R. CURTIS ◽  
HENRY A. GLICK ◽  
JEFFREY D. GREENBERG ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Statistical Power ◽  
Activity Index ◽  
Disease Activity Index ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Treatment Change ◽  
Disease Modifying

Objective.To evaluate the comparative effectiveness of nonbiologic disease-modifying antirheumatic drugs (DMARD) versus biologic DMARD (bDMARD) for treatment of rheumatoid arthritis (RA), using 2 common analytic approaches.Methods.We analyzed change in Clinical Disease Activity Index (CDAI) scores in patients with RA enrolled in a US-based observational registry from 2001 to 2008 using multivariable (MV) regression and propensity score (PS) matching. Among patients who initiated treatment with a nonbiologic DMARD (n = 1729), we compared patients who switched to, or added, another nonbiologic (n = 182) or a bDMARD (n = 342) at 5, 9, and 24 months after treatment change.Results.Both analytic approaches showed that patients switching to or adding another nonbiologic DMARD demonstrated improvement across 9 and 24 months (both p < 0.001). Both approaches also demonstrated greater improvement in CDAI among recipients of bDMARD relative to a second nonbiologic DMARD at 5 months (p < 0.02). The MV regression approach upheld these results at 9 and 24 months (p < 0.03). In contrast, the PS-matching approach did not show a sustained advantage with bDMARD at these later timepoints, possibly because of lower statistical power and/or lower baseline disease activity in the PS-matched cohort.Conclusion.Patients in both treatment groups generally experienced lower CDAI scores across time. Patients switching to bDMARD demonstrated greater improvement than patients switching to nonbiologic DMARD with both analytic approaches at 5 months. Relative advantages with bDMARD were observed at 9 and 24 months only with MV regression. These analyses provide a practical example of how findings in comparative effectiveness research can diverge with different methodological approaches.

scholarly journals Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

2021 ◽  
pp. annrheumdis-2021-219876
Author(s):  
Evgeniy Nasonov ◽  
Saeed Fatenejad ◽  
Eugen Feist ◽  
Mariana Ivanova ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Phase Iii ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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