scholarly journals Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study

2013 ◽  
Vol 73 (3) ◽  
pp. 536-543 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Hisashi Yamanaka ◽  
Naoki Ishiguro ◽  
Nobuyuki Miyasaka ◽  
Masaya Mukai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Japanese Patients ◽  
High Disease Activity ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Modified Total Sharp Score

ObjectivesTo evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics.MethodsThis randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26.ResultsA total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed.ConclusionsAdalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.

Five-year Favorable Outcome of Patients with Early Rheumatoid Arthritis in the 2000s: Data from the ESPOIR Cohort

2013 ◽  
Vol 40 (10) ◽  
pp. 1650-1657 ◽  
Author(s):  
Bernard Combe ◽  
Nathalie Rincheval ◽  
Joelle Benessiano ◽  
Francis Berenbaum ◽  
Alain Cantagrel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Health Assessment ◽  
Daily Practice ◽  
Joint Disease ◽  
Early Ra ◽  
American College Of Rheumatology ◽  
Biologic Dmard

Objective.To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome.Methods.Patients were recruited if they had early arthritis of < 6 months’ duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome.Results.We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression.Conclusion.The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.

scholarly journals Abatacept Plus Methotrexate Provides Incremental Clinical Benefits Versus Methotrexate Alone in Methotrexate-naive Patients with Early Rheumatoid Arthritis Who Achieve Radiographic Nonprogression

2011 ◽  
Vol 38 (11) ◽  
pp. 2362-2368 ◽  
Author(s):  
ALVIN F. WELLS ◽  
RENE WESTHOVENS ◽  
DIANE MONIZ REED ◽  
LUCIANA FANTI ◽  
JEAN-CLAUDE BECKER ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Disease Activity Score ◽  
Health Assessment ◽  
Joint Damage ◽  
Joint Disease ◽  
Activity Score ◽  
Double Blind ◽  
American College Of Rheumatology

Objective.This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase.Methods.Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit.Results.Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups.Conclusion.More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.

scholarly journals Efficacy and safety of upadacitinib over 84 weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE)

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Hideto Kameda ◽  
Tsutomu Takeuchi ◽  
Kunihiro Yamaoka ◽  
Motohiro Oribe ◽  
Mitsuhiro Kawano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Japanese Patients ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Dose Rates ◽  
American College Of Rheumatology

Abstract Background The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84 weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Methods All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30 mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30 mg QD. Efficacy and safety were assessed over 84 weeks. Results Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30 mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15 mg and 30 mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5 mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15 mg versus 30 mg. Conclusions Upadacitinib demonstrated sustained efficacy and was well tolerated over 84 weeks in Japanese patients with RA, with upadacitinib 15 mg offering the most favorable benefit–risk profile. Trial registration ClinicalTrials.gov NCT02720523. Registered on March 22, 2016.

Clinical Activity After 12 Weeks of Treatment with Nonbiologics in Early Rheumatoid Arthritis May Predict Articular Destruction 2 Years Later

2010 ◽  
Vol 37 (4) ◽  
pp. 723-729 ◽  
Author(s):  
YOICHI ICHIKAWA ◽  
TERUNOBU SAITO ◽  
HISASI YAMANAKA ◽  
MASASHI AKIZUKI ◽  
HIROBUMI KONDO ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Response To Treatment ◽  
Clinical Activity ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Core Set ◽  
Slow Progression ◽  
Biologic Dmard

Objective.To investigate earlier prediction of future articular destruction in patients with early rheumatoid arthritis (RA).Methods.We randomly allocated patients with RA with disease duration < 2 years to different nonbiologic disease modifying antirheumatic drug (DMARD) therapies in a double-blind trial. Progression of articular destruction over the 96-week treatment period was assessed using the modified Sharp method.Results.Progression of articular destruction correlated more strongly with the American College of Rheumatology (ACR) core set measures after 12 weeks of treatment than with pretreatment values. Multiple regression analysis of data after 12 weeks yielded a correlation coefficient of 0.711. The sensitivity and specificity to predict articular destruction over the 75th percentile of the cohort were 78.6% and 84.6%, respectively. Patients who showed articular destruction over the 75th percentile of the cohort had low response to treatment at 12 weeks, and continued to have high clinical disease activity thereafter. Contrasting data were found in patients with slow progression of articular destruction.Conclusion.In patients with early RA, ACR core set measures after 12 weeks of nonbiologic DMARD treatment may predict articular destruction 2 years later. Low response to treatment at 12 weeks and continuing high disease activity thereafter were found in patients with rapid radiological progression. These data can be used to determine the appropriateness of treatment at 12 weeks and aid the decision to introduce biologic DMARD.

SAT0046 MODIFIED DISEASE ACTIVITY SCORE AT 3 MONTHS IS A SIGNIFICANT PREDICTOR FOR RAPID RADIOGRAPHIC PROGRESSION AT 12 MONTHS COMPARED WITH OTHER MEASURES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 954.1-954
Author(s):  
M. Movahedi ◽  
D. Weber ◽  
P. Akhavan ◽  
E. Keystone
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Activity Score ◽  
Controlled Study ◽  
Tender Joint Count ◽  
Double Blind ◽  
Activity Measures ◽  
Disease Activity Measures

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease <3 years, were used. Only patients in the MTX arm were analyzed. RRP was defined as change in modified total Sharp (mTSS) > 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB

Efficacy and Safety of Belimumab in Patients with Rheumatoid Arthritis: A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study

2013 ◽  
Vol 40 (5) ◽  
pp. 579-589 ◽  
Author(s):  
William Stohl ◽  
Joan T. Merrill ◽  
James D. McKay ◽  
Jeffrey R. Lisse ◽  
Z. John Zhong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Phase Ii ◽  
B Lymphocyte ◽  
Tumor Necrosis Factor Inhibitor ◽  
Open Label ◽  
Double Blind ◽  
Acr20 Response ◽  
Link Type ◽  
American College Of Rheumatology

Objective.To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA).Methods.Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response.Results.Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups.Conclusion.In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812]

scholarly journals Low rates of radiographic progression of structural joint damage over 2 years of baricitinib treatment in patients with rheumatoid arthritis

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000898 ◽  
Author(s):  
Desirée van der Heijde ◽  
Michael Schiff ◽  
Yoshiya Tanaka ◽  
Li Xie ◽  
Gabriella Meszaros ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Combination Therapy ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Phase Iii ◽  
Inadequate Response ◽  
Smallest Detectable Change ◽  
Structural Joint ◽  
Synthetic Dmards ◽  
Modified Total Sharp Score

ObjectivesTo evaluate radiographic progression of structural joint damage over 2 years in patients with rheumatoid arthritis from baricitinib clinical trials who were disease-modifying antirheumatic drug (DMARD)–naïve or had an inadequate response to conventional synthetic DMARDs (csDMARD-IR).MethodsPatients had completed one of three phase III studies and entered a long-term extension (LTE) study, continuing on the same baricitinib dose as at originating study completion. At 52 weeks, DMARD-naïve patients receiving methotrexate (MTX) or combination therapy (baricitinib 4 mg+MTX) were switched to baricitinib 4 mg monotherapy (±MTX per investigator opinion); MTX-IR patients receiving adalimumab were switched to baricitinib 4 mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo were switched to baricitinib 4 mg on background csDMARD. Radiographs at baseline, year 1 and year 2 were scored using the van der Heijde modified Total Sharp Score. Linear extrapolation was used for missing data.ResultsOf 2573 randomised patients, 2125 (82.6%) entered the LTE, of whom 1893 (89.1%) entered this analysis. At year 2, progression was significantly lower with initial baricitinib (monotherapy or combination therapy) versus initial MTX in DMARD-naïve patients (proportion with non-progression defined by ≤smallest detectable change (SDC): 87.3% baricitinib 4 mg+MTX; 70.6% MTX; p≤ 0.001). In MTX-IR patients, progression with initial baricitinib was significantly lower than with initial placebo and similar to initial adalimumab (≤SDC: 82.7% baricitinib 4 mg; 83.5% adalimumab; 70.6% placebo; p≤0.001). In csDMARD-IR patients, significant benefit was seen with baricitinib 4 mg (≤SDC: 87.2% vs 73.2% placebo; p≤0.01).ConclusionsTreatment with once-daily baricitinib resulted in low rates of radiographic progression for up to 2 years.

Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

2020 ◽  
Vol 79 (4) ◽  
pp. 460-463 ◽  
Author(s):  
Mary Safy-Khan ◽  
Johannes W G Jacobs ◽  
Maria J H de Hair ◽  
Paco M J Welsing ◽  
Michael D Edwardes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety Outcomes ◽  
Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

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