scholarly journals Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis

RMD Open ◽  
2020 ◽  
Vol 6 (1) ◽  
pp. e001096 ◽  
Author(s):  
Josef S Smolen ◽  
Jung-Yoon Choe ◽  
Michael E Weinblatt ◽  
Paul Emery ◽  
Edward Keystone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Activity Index ◽  
Logistic Models ◽  
Disease Activity Index ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Tnf Inhibitor ◽  
Link Type

ObjectiveTo evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status.MethodsPatients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models.Results1265 patients were included. In all treatments combined, the 1 year mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI.ConclusionA pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity.Trial registration numbersNCT01895309, NCT01936181 and NCT02167139

scholarly journals Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies

2017 ◽  
Vol 45 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Christina Charles-Schoeman ◽  
Désirée van der Heijde ◽  
Gerd R. Burmester ◽  
Peter Nash ◽  
Cristiano A.F. Zerbini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Activity Index ◽  
Disease Activity Index ◽  
Response Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Link Type ◽  
Phase Iii Studies

Objective.Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies.Methods.Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)–erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire–Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score.Results.Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone.Conclusion.Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a trend to inhibit radiographic progression to a greater degree than MTX alone.

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.

scholarly journals Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: associations to future good radiographic and physical outcomes

2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Activity Index ◽  
Power Doppler ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Good Outcome ◽  
Grey Scale

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.

scholarly journals Investigating sirukumab for rheumatoid arthritis: 2-year results from the phase III SIRROUND-D study

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000731 ◽  
Author(s):  
Carter Thorne ◽  
Tsutomu Takeuchi ◽  
George Athanasios Karpouzas ◽  
Shihong Sheng ◽  
Regina Kurrasch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Clinical Signs ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Exposure Period ◽  
Phase Iii ◽  
Double Blind ◽  
Patient Reported

ObjectivesThe phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group SIRROUND-D study evaluated long-term efficacy and safety of the interleukin (IL)-6 inhibitor, sirukumab, in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drugs (DMARDs).MethodsPatients were randomised 1:1:1 to sirukumab 100  mg every 2 weeks (q2w), 50  mg every 4 weeks or placebo q2w subcutaneously. Patients initially randomised to placebo were rerandomised at Weeks 18, 40 or 52 to one of the sirukumab groups until Week 104.ResultsOf 1670 randomised patients, 1402 were included in the full analysis set and 1269 in the radiographic analysis set at Week 104. American College of Rheumatology scores, Disease Activity Score based on C-reactive protein, Clinical Disease Activity Index and clinically meaningful improvements in patient-reported outcomes were sustained at Week 104 among patients initially randomised to sirukumab. Placebo patients subsequently rerandomised to sirukumab showed clinical improvements at Week 104 that were comparable to results among patients initially randomised to sirukumab. Radiographic progression from Week 52 to Week 104 was comparable between all groups whether initially randomised to sirukumab or subsequently rerandomised to sirukumab from placebo. No new safety signals were identified in the extended exposure period compared with the initial 52 weeks of treatment.ConclusionsSirukumab treatment resulted in sustained reductions in clinical signs and symptoms and minimal progression in radiographic damage over 2 years among patients with RA refractory to DMARDs. The safety profile of sirukumab was as expected for an anti-IL-6 agent, with no new signals reported.

Effect of Remission Definition on Healthcare Cost Savings Estimates for Patients with Rheumatoid Arthritis Treated with Biologic Therapies

2014 ◽  
Vol 41 (8) ◽  
pp. 1600-1606 ◽  
Author(s):  
Cheryl Barnabe ◽  
Nguyen Xuan Thanh ◽  
Arto Ohinmaa ◽  
Joanne Homik ◽  
Susan G. Barr ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Healthcare Cost ◽  
Activity Index ◽  
Cost Savings ◽  
Disease Activity Index ◽  
Disease Status ◽  
Point Estimate ◽  
Sustained Remission ◽  
American College Of Rheumatology

Objective.Sustained remission in rheumatoid arthritis (RA) results in healthcare utilization cost savings. We evaluated the variation in estimates of savings when different definitions of remission [2011 American College of Rheumatology/European League Against Rheumatism Boolean Definition, Simplified Disease Activity Index (SDAI) ≤ 3.3, Clinical Disease Activity Index (CDAI) ≤ 2.8, and Disease Activity Score-28 (DAS28) ≤ 2.6] are applied.Methods.The annual mean healthcare service utilization costs were estimated from provincial physician billing claims, outpatient visits, and hospitalizations, with linkage to clinical data from the Alberta Biologics Pharmacosurveillance Program (ABioPharm). Cost savings in patients who had a 1-year continuous period of remission were compared to those who did not, using 4 definitions of remission.Results.In 1086 patients, sustained remission rates were 16.1% for DAS28, 8.8% for Boolean, 5.5% for CDAI, and 4.2% for SDAI. The estimated mean annual healthcare cost savings per patient achieving remission (relative to not) were SDAI $1928 (95% CI 592, 3264), DAS28 $1676 (95% CI 987, 2365), and Boolean $1259 (95% CI 417, 2100). The annual savings by CDAI remission per patient were not significant at $423 (95% CI −1757, 2602). For patients in DAS28, Boolean, and SDAI remission, savings were seen both in costs directly related to RA and its comorbidities, and in costs for non-RA-related conditions.Conclusion.The magnitude of the healthcare cost savings varies according to the remission definition used in classifying patient disease status. The highest point estimate for cost savings was observed in patients attaining SDAI remission and the least with the CDAI; confidence intervals for these estimates do overlap. Future pharmacoeconomic analyses should employ all response definitions in assessing the influence of treatment.

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.

scholarly journals Rheumatoid arthritis disease activity index-5: Utility in busy clinical settings

2017 ◽  
Vol 12 (2) ◽  
pp. 72
Author(s):  
VikramSingh Tanwar ◽  
Harpreet Singh ◽  
Gagandeep Sukhija ◽  
Rekha Mathur ◽  
Parminder Kaur
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Settings ◽  
Rheumatoid Arthritis Disease Activity ◽  
Rheumatoid Arthritis Disease

scholarly journals Rate of hypovitaminosis D and association of plasma concentration of 25(OH)D with indicators of disease activity in patients with rheumatoid arthritis

2020 ◽  
Vol 64 (6) ◽  
pp. 723-729
Author(s):  
A. V. Rudenko ◽  
T. D. Tyabut ◽  
A. E. Buglova ◽  
G. A. Babak ◽  
P. M. Morozik ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Disease Activity ◽  
Vitamin D Deficiency ◽  
Activity Index ◽  
Serum Vitamin ◽  
Disease Activity Index ◽  
Tender Joint Count ◽  
Serum Vitamin D ◽  
Vitamin D Levels

Vitamin D deficiency is an important environmental risk factor that influences the prevalence and severity of several autoimmune diseases, including rheumatoid arthritis (RA). The aim of this study was to determine the incidence of vitamin D insufficiency and deficiency in patients with RA, to establish the relationship between serum vitamin D levels and indicators of disease activity. 156 patients with RA were included in the study, mean age 60.2 ± 13.9 years. Assessment of clinical status was performed, serum concentrations of rheumatoid factor (RF), C-reactive protein (CRP), total vitamin D (25(OH)D), antibodies to cyclic citrullinated peptide (ACCP) were determined. RA disease activity was evaluated using DAS28 (disease activity score), SDAI (Simplified Disease Activity Index) и CDAI (Clinical Disease Activity Index) scores. Average levels of 25(OH)D in the surveyed sample were 25.2 ± 13.2 ng/ml. The results of the study indicate a high prevalence of vitamin D deficiency in patients with RA. Normal indicators of vitamin D, its insufficiency and deficiency were observed in 47 (30.3 %), 45 (28.7 %) and 64 (40.7 %) patients, respectively. Low level of serum 25(OH)D was associated with higher indices of RA activity according to DAS28, SDAI and CDAI, as well as with greater tender joint count. Vitamin D should be prescribed as an adjunctive therapy in patients with active RA due to its potential immunomodulatory effect, as well as for the prevention and treatment of bone metabolism disorders.

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