scholarly journals AB0365 COMPARISON OF SUSTAINED CLINICAL REMISSION AND/OR LOW DISEASE ACTIVITY RATE BETWEEN RAPIDLY AND GRADUALLY DE-ESCALATION OF BARICITINIB IN RHEUMATOID ARTHRITIS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1483.2-1483
Author(s):  
M. Yamasaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Janus Kinase ◽  
Biologic Dmards ◽  
Low Disease Activity ◽  
First Line Therapy

Background:However baricitinib, an oral selective inhibitor of Janus kinase (JAK) 1 and 2, improved signs and symptoms of rheumatoid arthritis (RA), it is unknown who can taper or stop baricitinib and strategies for de-escalation.Objectives:We analyze predictors of tapering of withdrawal failure in rheumatoid arthritis (RA) patients treated with baricitinib. This study will assess and compare (1) characteristic of patients who achieve remission (REM) or low disease activity (LDA) as who can taper baricitinib and (2) two de-escalation methods, rapidly and gradually de-escalation in patients who respond first-line therapy.Methods:Cases were recruited to SHin-yokohama Arthritis REgister (SHARE) between 2015 and 2019 (n=3,674). Patients were diagnosed according to ACR/EULAR 2010 classification criteria, and treated with DMARDs which included baricitinib 2mg/day (n=154). In 154 cases, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI), anti-CCP2 and patients clinical parameters were analyzed. Two de-escalation methods were compared in this study. In rapidly de-escalation methods, baricitinib were stopped in patients with stable REM/LDA over 12 weeks. In gradually de-escalation methods, baricitinib were decreased to 50%, 42%, 28%, 14% in order with stable REM/LDA over 12 weeks.Results:In 154 (Male25, Female129 cases, RA duration 11.4+/-8.0 years) cases, CDAI at baricitinib-start was 20.6+/-12.4 and titer of anti-CCP2 was 242.6+/-516.5 U/ml. 126 cases (81.8%) were more than 2 years of RA duration and 49 cases (31.8%) had persistency of signs and/or symptoms suggestive of inflammatory RA disease activitiy, despite prior treatment with csDMARDs and at least two biologic DMARDs. 33 cases (21.4%) were biologic DMARDs naive.(1)”Multivariate logistic regression examined the predictors to detect who can taper baricitinib” However there were no differences in duration of RA, onset age of RA, biologics and/or JAK inhibitors naïve, anti-CCP2 titer and CDAI at the start baricitinib, patients who showed decrease of CDAI at 12 weeks were correlated with achievement of remission (REM) or low disease activity (LDA) in patients treated with baricitinib (OR 0.964, 95%CI 0.934-0.996, p=0.010). ROC analysis of ΔCDAI at 12 weeks is cut-off value of -6.6 (p=0.011).(2)”Comparison of sustained REM and/or LDA rate between rapidly and gradually de-escalation of baricitinib in rheumatoid arthritis” 11 cases were tapered baricitinib with rapidly de-escalation methods and 60 patients were with gradually de-escalation. Mean times to start taper baricitinib in rapidly and gradually de-escalation group were 4.6+/-1.6 months and 5.9+/-2.2 months respectively. Gradually de-escalation methods showed less relapse rate compared with rapidly de-escalation after tapered baricitinib for 6 months (18.3% vs. 54.5%, p=0.018). There were no differences in clinical features such as anti-CCP2, CDAI and administration period of baricitinib between non-relapse and relapse patients in gradually escalation methods.Conclusion:A combination of ΔCDAI at 12 weeks and tapering baricitinib using gradually de-escalation methods may help to predict successful baricitinib deduction in RA patients with sustained clinical REM and/or LDA.References:[1]Ann Rheum Dis. 2019;78:171[2]Rheumatology. 2019;58:110[3]An Rheum Dis. 2015;74:19Disclosure of Interests:None declared

OP129 Predictors Of Effectiveness In Patients With Rheumatoid Arthritis

2017 ◽  
Vol 33 (S1) ◽  
pp. 59-60
Author(s):  
Jéssica dos Santos ◽  
Haliton Oliveira ◽  
Francisco Acurcio Michael da Silva ◽  
Alessandra Almeida ◽  
Flávia Rodrigues ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Univariate Analysis ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Chi Square ◽  
Low Disease Activity ◽  
Gender Education

INTRODUCTION:Biological disease-modifying anti-rheumatic drugs (bDMARDs) have become firmly established in the management of patients with rheumatoid arthritis (RA), but some patients do not improve despite therapy. This study evaluated the predictors of effectiveness of the bDMARDs on a cohort of patients with rheumatoid arthritis (RA) in the Brazilian Public Health System.METHODS:RA individuals treated with bDMARDs, were included in the open prospective cohort study. The Clinical Disease Activity Index (CDAI) was used to assess the effectiveness comparing results at baseline and after 6 months of follow-up. The association between socio-demographic and clinical characteristics with the disease activity measured by the CDAI was also investigated. The bDMARDs was considered effective when the patient achieved remission or low disease activity and considered not effective when there was still moderate or high disease activity. Pearson's chi-square was applied for the univariate analysis to evaluate the association of effectiveness measured by the CDAI with the socio-demographic (gender, education, marital status and race) and clinical variables (type of drug, EuroQol (EQ)-5D and Health Assessment Questionnaire (HAQ)). Logistic regression was applied in the multivariate analysis of the variables that presented a p< .20 value during the univariate analysis.RESULTS:All 266 RA patients completed six months of follow-up. The most widely used bDMARDs was adalimumab (57.1 percent), with etanercept used by 22.2 percent, golimumab by 7.5 percent, abatacept by 4.5 percent, tocilizumab by 3.4 percent, infliximab by 2.6 percent, certolizumab by 1.5 percent, and rituximab by 1.1 percent. The bDMARDs reduced disease activity as measured by CDAI at six months of follow-up (p<.001). The percentage of patients achieving remission or low disease activity was 40.6 percent. bDMARDs were more effective in patients with better functionality (Odds Ratio, OR = 2.140 / 95 percent Confidence Interval, CI 1.219 - 3.756) at beginning of treatment and in patients who not had a previous bDMARDs (OR = 2.150 / 95 percent CI 1.144 - 4.042).CONCLUSIONS:In this real-world study, functionality and use of previous bDMARDs are predictors in patients with RA treated with bDMARDs.

scholarly journals Effectiveness and Safety of Subcutaneous Abatacept in Biologic-Naïve RA Patients at Week 52: A Japanese Multicenter Investigational Study (ORIGAMI Study)

2021 ◽  
Author(s):  
Naoto Tamura ◽  
Takanori Azuma ◽  
Kenta Misaki ◽  
Rei Yamaguchi ◽  
Fuminori Hirano ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Treatment Retention ◽  
Low Disease Activity ◽  
Moderate Disease ◽  
Moderate Disease Activity

Abstract Objectives To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan. Methods Abatacept 125 mg was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension (EQ-5D), treatment retention, and safety. Results were compared with those of csDMARD controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry. Results Overall, 325 patients were enrolled, with a mean age of 66.9±12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3–23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4–59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7–75.5). AEs and serious AEs were reported in 50.0% and 12.1% of patients, respectively. Conclusions Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting.

scholarly journals Early non-response to certolizumab pegol in rheumatoid arthritis predicts failure to achieve low disease activity at 1 year: data from a prospective observational study

RMD Open ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e000991 ◽  
Author(s):  
Alain Saraux ◽  
René-Marc Flipo ◽  
Francis Fagnani ◽  
Jacques Massol ◽  
Gabrielle Cukierman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Certolizumab Pegol ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Low Disease Activity ◽  
Clinical Criteria ◽  
Late Treatment ◽  
Clinical Measures

ObjectiveTo evaluate the performance of clinical criteria for predicting late treatment failure in patients with early non-response to certolizumab pegol (CZP).MethodsA protocol-specified analysis of interim data from ECLAIR, a 3-year longitudinal, prospective, observational, multicentre study of patients with active rheumatoid arthritis (RA) initiating CZP treatment in France, was conducted. Clinical measures assessed were Clinical Disease Activity Index (CDAI), Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28(ESR)) and Health Assessment Questionnaire Disability Index (HAQ-DI). Early non-response was measured at 3 months (M3) and failure to achieve low disease activity (LDA) at 12 months (M12).Results574/792 enrolled patients were treated at M3. The numbers available for predictability analyses were 532 (CDAI), 434 (DAS28(ESR)) and 496 (HAQ-DI). Of the three indices evaluated, the highest predictor of non-response value was observed for the CDAI (88.8% (95% CI 81.0 to 94.1)), indicating that up to 88% of patients identified as non-responders at M3 failed to achieve LDA at M12, regardless of baseline disease severity or treatment history. The specificity for this measure was also very high (96.0%), indicating that less than 5% of patients who achieved CDAI response at M12 had not responded at M3. Similar predictability was observed for DAS28(ESR), but only in patients with high disease activity at baseline and/or those previously treated by a biological disease-modifying antirheumatic drug.ConclusionCDAI non-response at M3 is a predictor of failure to achieve the therapeutic target of LDA at M12 in patients with RA initiating treatment with CZP.

scholarly journals AB0271 COMPARISON OF DOSE REDUCTION METHODS BETWEEN RAPIDLY AND GRADUALLY DE-ESCALATION IN RHEUMATOID ARTHRITIS TREATED WITH BARICITINIB OVER 15 MONTHS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1162.1-1162
Author(s):  
M. Yamasaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Relapse Rate ◽  
Activity Index ◽  
Health Assessment ◽  
Treatment Strategies ◽  
Disease Activity Index ◽  
Jak Inhibitors ◽  
First Line Therapy ◽  
Reduction Methods

Background:However tsDMARDs and treatment strategies have improved the outcomes of rheumatoid arthritis (RA), it is unknown who can taper or stop tsDMARDs and strategies for de-escalation.Objectives:We analyze predictors of de-escalation in RA patients treated with baricitinib over 15 months in each group who start baricitinib with 4mg/day and 2mg/day.This study will assess and compare (1) characteristic of patients who achieve remission (REM) or low disease activity (LDA) as who can taper baricitinib and (2) two de-escalation methods, rapidly and gradually de-escalation in patients who respond first-line therapy.Methods:Cases were recruited to SHin-yokohama Arthritis REgister (SHARE) between 2015 and 2020 (n=3,961). Patients were diagnosed according to ACR/EULAR 2010 classification criteria and treated with baricitinib started with 4mg/day(n=42) or 2mg/day(n=108) over 15 months. 45 cases fulfilled EULAR definition for difficult-to-treat RA (D2T-RA). In 150 (Male25, Female125 cases, RA duration 12.5+/-5.9years) cases, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI), anti-CCP2 and clinical parameters were analyzed. Two de-escalation methods were compared in this study. In rapidly de-escalation methods, baricitinib were stopped in patients with stable REM/LDA with no swollen joint over 12 weeks. In gradually de-escalation methods, baricitinib were decreased to 50%, 42%, 28%, 14% in order with stable REM/LDA with no swollen joint over 12 weeks.Results:(1)” Detect predictors who can achieve REM/LDA with no swollen joint as starting de-escalation baricitinib” In patients started with baricitinib 4mg/day group, 17 patients achieved REM/LDA with no swollen joint(40.5%), there were no differences in duration of RA, onset age of RA, biologics and/or JAK inhibitors naïve, anti-CCP2 titer and CDAI at the start baricitinib between REM/LDA and non-achieved cases. In patients started with baricitinib 2mg/day group, 59 patients achieved REM/LDA with no swollen joint (54.6%). In 2mg/day group, biologics and/or JAK inhibitors naïve was predictor for achieving REM/LDA with no swollen joint. In 2mg/day group, D2T-RA patients was negative predictor.(2)”Comparison of sustained REM and/or LDA rate between rapidly and gradually de-escalation of baricitinib in rheumatoid arthritis” In whole patients, 15 patients were tapered baricitinib with rapidly de-escalation methods and 61 patients were with gradually de-escalation. Gradually de-escalation methods showed less relapse rate compared with rapidly de-escalation after tapered baricitinib (33.3% vs. 93.8%, p<0.0001). Particularly in 2mg/day group, 12 patients were tapered baricitinib with rapidly de-escalation methods and 47 patients were with gradually de-escalation. Gradually de-escalation methods showed less relapse rate compared with rapidly de-escalation after tapered baricitinib for 32.7 months (33.3% vs. 80.9%, p<0.0001). However 2cases in 4mg/day group and 8cases in 2mg/day showed increase of CDAI, all these cases regain LDA after increasing baricitinib.Conclusion:Tapering baricitinib using gradually de-escalation methods may help to sucseed deduction of baricitinib in RA patients with sustained clinical REM and/or LDA with no swollen joint in each group who start baricitinib with 4mg/day and 2mg/day.References:[1]Ann Rheum Dis 2019;78:171-178Disclosure of Interests:None declared

scholarly journals Effectiveness of Rituximab for the Treatment of Rheumatoid Arthritis in Patients with Prior Exposure to Anti-TNF: Results from the CORRONA Registry

2015 ◽  
Vol 42 (7) ◽  
pp. 1090-1098 ◽  
Author(s):  
Leslie R. Harrold ◽  
George W. Reed ◽  
Ashwini Shewade ◽  
Robert Magner ◽  
Katherine C. Saunders ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Effectiveness ◽  
High Disease Activity ◽  
Low Disease Activity ◽  
Logistic Regression Models ◽  
Lower Baseline ◽  
Previously Treated

Objective.To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis.Methods.Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models.Results.Patients (n = 265) were followed for 12 months with a mean change in CDAI of −8.1 (95% CI −9.8 – −6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of −10.1 (95% CI −13.2 – −7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of −10.5 (95% CI −12.9 – −8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22–0.73), which was robust to 4 different adjusted models (OR range 0.38–0.44).Conclusion.A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.

THU0620-HPR MEASUREMENT OF LOW DISEASE ACTIVITY USING THE CLINICAL DISEASE ACTIVITY INDEX (CDAI) VERSUS THE DISEASE ACTIVITY SCORE 28 (DAS 28): IMPACT OF INFLAMMATION MARKERS ON THE COMPARATIVE EFFECTIVENESS OF BIOLOGICS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Janke ◽  
K. Biester ◽  
D. Krause ◽  
B. Richter ◽  
C. Schürmann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Acute Phase Reactants ◽  
Das 28 ◽  
Effectiveness Studies

Background:Biologics for the treatment of rheumatoid arthritis (RA) have different modes of action to target auto-inflammatory processes causing the signs and symptoms of the disease. Different biologics may thus have different effects on inflammatory markers. For instance, previous studies have shown that the interleukin-6-inhibitor tocilizumab (TOC) decreases the level of acute phase reactants (APRs) [1]. Such direct effects on inflammatory markers may lead to an overestimation of clinical response if disease activity is measured via scores including inflammatory markers, such as the Disease Activity Score 28 (DAS 28). The detected changes in disease activity may not adequately reflect the clinical improvement of signs and symptoms.Objectives:In our study, we compared biologics with each other using two different disease activity scores: the DAS 28 including APRs and the clinical disease activity index (CDAI) excluding APRs. The aim of this study was to assess whether the use of the two different scores affects comparative effectiveness studies on biologics for the treatment of RA.Methods:We compared results on the comparative effectiveness of biologics using the corresponding thresholds for low disease activity (LDA) for the DAS 28 (< 3.2) and the CDAI (≤ 10). We performed two separate network meta-analyses (NMAs) after a thorough step-by-step evaluation of the similarity, homogeneity and consistency assumptions of the patient populations and the study data.Our study formed part of a systematic review (including NMAs) that was largely based on clinical study reports and re-analyses of LDA using individual patient data provided by sponsors for studies conducted up to 2017. Thus, the analyses include hitherto unknown data on LDA analysed by means of the CDAI, especially data from older studies. An extensive comparison of DAS 28 and CDAI in different patient populations was possible.Results:For all analysed patient populations, comparisons of TOC versus other biologics yielded remarkable results: advantages for TOC were found in NMAs using the DAS 28, which were not confirmed in NMAs using the CDAI. For methotrexate (MTX)-naïve patients, using the DAS 28, TOC showed a greater benefit than abatacept (ABA), certolizumab pegol (CZP), and etanercept (ETA), which was not confirmed by the CDAI. In contrast, TOC showed less benefit than adalimumab (ADA) and ETA. For patients after MTX failure and using the DAS 28, TOC showed a greater benefit than ABA, ADA, anakinra (ANA), ETA, golimumab (GOL), and infliximab (INF). With the exception of ANA, these advantages were not confirmed by the CDAI. Similar differences between DAS 28 and CDAI were shown in patients treated with biologics in monotherapy or after failure of biologics.Conclusion:In comparative effectiveness studies of biologics, the assessment of LDA using the DAS 28 instead of the CDAI leads to a consistent overestimation of the benefit of TOC in all patient populations, regardless of pre-treatment or combined therapy with MTX. The inclusion of APRs in disease activity scores may thus introduce bias. A score excluding inflammatory markers should therefore be used to ensure valid results.References:[1]Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011; 63(1): 43-52.Disclosure of Interests:Kirsten Janke: None declared, Katharina Biester: None declared, Dietmar Krause Grant/research support from: Pfizer and AbbVie (Abbott), Bernd Richter: None declared, Christoph Schürmann: None declared, Katharina Hirsch: None declared, Beate Wieseler: None declared

scholarly journals Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2020-218412
Author(s):  
Roy M Fleischmann ◽  
Ricardo Blanco ◽  
Stephen Hall ◽  
Glen T D Thomson ◽  
Filip E Van den Bosch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Kinase Inhibitor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Initial Therapy ◽  
Janus Kinase ◽  
Treat To Target ◽  
Efficacy And Safety ◽  
Insufficient Response

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

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.

scholarly journals Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

2016 ◽  
Vol 76 (6) ◽  
pp. 1009-1019 ◽  
Author(s):  
A Kavanaugh ◽  
J Kremer ◽  
L Ponce ◽  
R Cseuz ◽  
O V Reshetko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Active Rheumatoid Arthritis ◽  
Activity Index ◽  
Disease Activity Index ◽  
Rapid Onset ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Onset Of Action ◽  
End Points

ObjectivesTo evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).MethodsIn this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.ResultsOverall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported.ConclusionsOver 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.Trial registration numberNCT01894516.

scholarly journals Estimation of a numerical value for joint damage-related physical disability in rheumatoid arthritis clinical trials

2009 ◽  
Vol 69 (6) ◽  
pp. 1058-1064 ◽  
Author(s):  
Josef S Smolen ◽  
Daniel Aletaha ◽  
Johannes C Grisar ◽  
Tanja A Stamm ◽  
John T Sharp
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Health Assessment ◽  
Joint Damage ◽  
Disease Activity Index ◽  
Controlled Clinical Trial ◽  
Short Term ◽  
Randomised Controlled ◽  
Radiographic Changes

BackgroundJoint damage is an important outcome in trials of rheumatoid arthritis (RA), usually assessed by Total Sharp Score (TSS). It is currently unknown how it translates numerically into disability by the Health Assessment Questionnaire (HAQ).ObjectiveTo determine the units of HAQ score corresponding to one TSS unit.MethodsA short-term observational trial of glucocorticoids in RA (the ‘BEst LIfe with Rheumatoid Arthritis’ (BELIRA) trial) was evaluated, using randomised controlled clinical trial (RCT) data for confirmation. For each trial arm HAQ, TSS and the Simplified Disease Activity Index (SDAI) were assessed. Based on the hypothesis that short-term HAQ changes will mostly be due to changes of disease activity, activity HAQ (ACT-HAQ) at end point (EP) was determined and remaining disability defined as damage related (DAM-HAQ). Using TSS at EP, the HAQ units corresponding to a TSS unit were estimated.ResultsIn BELIRA, one TSS unit corresponded to a mean of 0.017 HAQ units; to account for other causes of irreversible disability, the 25th percentile was used: 0.011 HAQ units/TSS unit. In RCT trial arms, the HAQ/TSS were similar (0.013 and 0.015 in established and early RA, respectively; 25th percentile: 0.010). The correlation between DAM-HAQEP and TSS was r=0.829. Over 5 years, damage would amount to an increase of irreversible HAQ of 0.33 on placebo, 0.13 on disease-modifying antirheumatic drugs (DMARDs) and 0.03 on TNF inhibitors+methotrexate (MTX).ConclusionAn approach to estimate the numerical relationship between HAQ and damage as 0.01 HAQ points/TSS unit is presented, although the linear relationship may not be generally valid. This allows the assessment of functional correlates of radiographic changes in trials.

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