Long-term safety, efficacy and inhibition of radiographic progression with abatacept treatment in patients with rheumatoid arthritis and an inadequate response to methotrexate: 3-year results from the AIM trial

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.

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Longterm Safety, Efficacy, and Inhibition of Structural Damage Progression Over 5 Years of Treatment with Abatacept in Patients with Rheumatoid Arthritis in the Abatacept in Inadequate Responders to Methotrexate Trial

The Journal of Rheumatology ◽

10.3899/jrheum.130263 ◽

2014 ◽

Vol 41 (6) ◽

pp. 1077-1087 ◽

Cited By ~ 23

Author(s):

Joel M. Kremer ◽

Charles Peterfy ◽

Anthony S. Russell ◽

Paul Emery ◽

Carlos Abud-Mendoza ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Structural Damage ◽

Radiographic Progression ◽

Health Assessment ◽

Incidence Rates ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

American College Of Rheumatology ◽

Inadequate Responders

Objective.Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores.Results.Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire–Disability Index at Year 1 [–2.83 (n = 365) and −0.68 (n = 369)] were maintained at Year 5 [−3.14 (n = 264) and −0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively.Conclusion.In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.

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Subcutaneous Abatacept for the Treatment of Rheumatoid Arthritis: Longterm Data from the ACQUIRE Trial

The Journal of Rheumatology ◽

10.3899/jrheum.130112 ◽

2014 ◽

Vol 41 (4) ◽

pp. 629-639 ◽

Cited By ~ 23

Author(s):

Mark C. Genovese ◽

César Pacheco Tena ◽

Arturo Covarrubias ◽

Gustavo Leon ◽

Eduardo Mysler ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Severe Disease ◽

Incidence Rates ◽

Phase Iii ◽

Inadequate Response ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Safety And Efficacy ◽

Link Type

Objective.Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).Methods.The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.Results.Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8–44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.Conclusion.These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-216537 ◽

2020 ◽

Vol 79 (4) ◽

pp. 460-463 ◽

Cited By ~ 3

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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Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial

The Journal of Rheumatology ◽

10.3899/jrheum.170344 ◽

2018 ◽

Vol 45 (8) ◽

pp. 1085-1092 ◽

Cited By ~ 13

Author(s):

Mark C. Genovese ◽

César Pacheco-Tena ◽

Arturo Covarrubias ◽

Gustavo Leon ◽

Eduardo Mysler ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Inadequate Response ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Multinational Trial ◽

Serious Infection ◽

Longterm Treatment ◽

Phase Iiib ◽

Inadequate Responders

Objective.To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported.Results.Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96–8.58), infection 38.60 (36.24–41.12), serious infection 1.68 (1.35–2.07), malignancies 1.09 (0.84–1.42), and autoimmune disorders 1.33 (1.05–1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study.Conclusion.These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

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

The Journal of Rheumatology ◽

10.3899/jrheum.120886 ◽

2013 ◽

Vol 40 (5) ◽

pp. 579-589 ◽

Cited By ~ 58

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]

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Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214729 ◽

2019 ◽

Vol 78 (6) ◽

pp. 754-760 ◽

Cited By ~ 14

Author(s):

Sudha Visvanathan ◽

Stefan Daniluk ◽

Rafał Ptaszyński ◽

Ulf Müller-Ladner ◽

Meera Ramanujam ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Bone Resorption ◽

Primary Endpoint ◽

Study Drug ◽

Nuclear Factor Κb ◽

Inadequate Response ◽

Serious Adverse Events ◽

Double Blind ◽

Autoantibody Production ◽

Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

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Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214943 ◽

2019 ◽

Vol 78 (8) ◽

pp. 1033-1040 ◽

Cited By ~ 9

Author(s):

Sophie Glatt ◽

Peter C Taylor ◽

Iain B McInnes ◽

Georg Schett ◽

Robert Landewé ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Certolizumab Pegol ◽

Inadequate Response ◽

Proof Of Concept ◽

Efficacy And Safety ◽

Open Label ◽

Double Blind ◽

Reactive Protein ◽

Dual Inhibition

ObjectiveEvaluate the efficacy and safety of dual neutralisation of interleukin (IL)-17A and IL-17F with bimekizumab, a monoclonal IgG1 antibody, in addition to certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) and inadequate response (IR) to certolizumab pegol.MethodsDuring this phase 2a, double-blind, proof-of-concept (PoC) study (NCT02430909), patients with moderate-to-severe RA received open-label CZP 400 mg at Weeks 0, 2 and 4, and 200 mg at Week 6. Patients with IR at Week 8 (Disease Activity Score 28-joint count C-reactive protein (DAS28(CRP))>3.2) were randomised 2:1 to CZP (200 mg every 2 weeks (Q2W)) plus bimekizumab (240 mg loading dose then 120 mg Q2W) or CZP plus placebo. The primary efficacy and safety variables were change in DAS28(CRP) between Weeks 8 and 20 and incidence of treatment-emergent adverse events (TEAEs).ResultsOf 159 patients enrolled, 79 had IR at Week 8 and were randomised to CZP plus bimekizumab (n=52) or CZP plus placebo (n=27). At Week 20, there was a greater reduction in DAS28(CRP) in the CZP-IR plus bimekizumab group compared with the CZP-IR plus placebo group (99.4% posterior probability). The most frequent TEAEs were infections and infestations (CZP plus bimekizumab, 50.0% (26/52); CZP plus placebo, 22.2% (6/27)).ConclusionsPoC was confirmed based on the rapid decrease in disease activity achieved with 12 weeks of CZP plus bimekizumab. No unexpected or new safety signals were identified when neutralising IL-17A and IL-17F in patients with RA concomitantly treated with CZP, but the rate of TEAEs was higher with dual inhibition.

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Longterm Safety and Efficacy of Subcutaneous Tocilizumab Monotherapy: Results from the 2-year Open-label Extension of the MUSASHI Study

The Journal of Rheumatology ◽

10.3899/jrheum.140665 ◽

2015 ◽

Vol 42 (5) ◽

pp. 799-809 ◽

Cited By ~ 27

Author(s):

Atsushi Ogata ◽

Koichi Amano ◽

Hiroaki Dobashi ◽

Masayuki Inoo ◽

Tomonori Ishii ◽

...

Keyword(s):

Adverse Events ◽

Disease Activity ◽

Additional Treatment ◽

Joint Disease ◽

Open Label ◽

Serious Adverse Events ◽

Double Blind ◽

Safety And Efficacy ◽

American College Of Rheumatology ◽

Open Label Extension

Objective.To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA).Methods.Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks.Results.The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy.Conclusion.TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

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Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.074773 ◽

2007 ◽

Vol 67 (4) ◽

pp. 547-554 ◽

Cited By ~ 180

Author(s):

M C Genovese ◽

M Schiff ◽

M Luggen ◽

J-C Becker ◽

R Aranda ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Adverse Events ◽

Sleep Problems ◽

Inadequate Response ◽

C Reactive Protein ◽

Double Blind ◽

Safety And Efficacy ◽

Reactive Protein ◽

Sf 36

Objective:To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis.Methods:Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept ∼10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 (C-reactive protein), HAQ-DI, SF-36, Medical Outcomes Study Sleep Problems Index, fatigue VAS) were assessed through 2 years.Results:317 patients (218 from the abatacept and 99 from the placebo group) entered and 222 (70%) completed 18 months of long-term extension treatment. The incidence and type of adverse events were consistent between the double-blind and cumulative (double-blind plus long-term extension) periods. Rates of serious adverse events were 25.6 and 23.4 per 100 patient-years in the double-blind versus cumulative period. At 6 months and 2 years, using non-responder analyses, ACR responses in abatacept-treated patients were: ACR 20, 59.4% and 56.2%; ACR 50, 23.5% and 33.2%; ACR 70, 11.5% and 16.1%; HAQ-DI responses were 54.4% and 47.9%. At 6 months and 2 years, using post-hoc as-observed analyses, the percentage of patients (95% confidence interval) achieving DAS28 (C-reactive protein) low disease activity score (⩽3.2) and DAS28 (C-reactive protein)-defined remission (<2.6) increased from 18.3% (13.0, 23.5) to 32.0% (24.6, 39.4) and 11.1% (6.8, 15.3) to 20.3% (13.9, 26.6). Clinically meaningful improvements in SF-36, pain, fatigue and sleep problems were also maintained throughout the 2 years of abatacept treatment.Conclusion:No unique safety observations were reported during open-label exposure. Improvements in the signs and symptoms of rheumatoid arthritis, physical function and health-related quality of life observed after 6 months, were maintained throughout the 2 years in this population with difficult-to-treat disease.Trial registration number:NCT00124982.

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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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-202433 ◽

2013 ◽

Vol 73 (3) ◽

pp. 536-543 ◽

Cited By ~ 59

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.

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