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Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).

Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, Genant HK, Peterfy C, Mitra P, Overfield S, Qi K, Westhovens R - Ann. Rheum. Dis. (2009)

Bottom Line: Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.Abatacept delayed progression of UA/very early RA in some patients.This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds. p.emery@leeds.ac.uk [corrected]

ABSTRACT

Background: Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.

Objective: To determine the impact of T-cell costimulation modulation in patients with UA or very early RA.

Methods: In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years.

Results: At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.

Conclusion: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.

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Patient disposition over 2 years. AE, adverse event.
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Figure 1: Patient disposition over 2 years. AE, adverse event.

Mentions: Figure 1 shows the patient disposition. Over 6 months of treatment, 6/28 (21.4%) patients in the abatacept group and 11/28 (39.3%) patients in the placebo group discontinued; of these, three (10.7%) and eight (28.6%) were owing to lack of efficacy, respectively. After treatment cessation, from month 6 to year 2, 15 (53.6%) and 13 (46.4%) patients randomised to the original abatacept and placebo groups discontinued, respectively; 11 (39.3%) and 12 (42.9%) of these were owing to lack of efficacy. Seven (25.0%) and four (14.3%) patients randomised to abatacept and placebo completed 2 years, respectively.


Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial).

Emery P, Durez P, Dougados M, Legerton CW, Becker JC, Vratsanos G, Genant HK, Peterfy C, Mitra P, Overfield S, Qi K, Westhovens R - Ann. Rheum. Dis. (2009)

Patient disposition over 2 years. AE, adverse event.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2927615&req=5

Figure 1: Patient disposition over 2 years. AE, adverse event.
Mentions: Figure 1 shows the patient disposition. Over 6 months of treatment, 6/28 (21.4%) patients in the abatacept group and 11/28 (39.3%) patients in the placebo group discontinued; of these, three (10.7%) and eight (28.6%) were owing to lack of efficacy, respectively. After treatment cessation, from month 6 to year 2, 15 (53.6%) and 13 (46.4%) patients randomised to the original abatacept and placebo groups discontinued, respectively; 11 (39.3%) and 12 (42.9%) of these were owing to lack of efficacy. Seven (25.0%) and four (14.3%) patients randomised to abatacept and placebo completed 2 years, respectively.

Bottom Line: Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.Abatacept delayed progression of UA/very early RA in some patients.This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds. p.emery@leeds.ac.uk [corrected]

ABSTRACT

Background: Several agents provide treatment for established rheumatoid arthritis (RA), but a crucial therapeutic goal is to delay/prevent progression of undifferentiated arthritis (UA) or very early RA.

Objective: To determine the impact of T-cell costimulation modulation in patients with UA or very early RA.

Methods: In this double-blind, phase II, placebocontrolled, 2-year study, anti-cyclic citrullinated peptide (CCP)2-positive patients with UA (not fulfilling the ACR criteria for RA) and clinical synovitis of two or more joints were randomised to abatacept ( approximately 10 mg/kg) or placebo for 6 months; the study drug was then terminated. The primary end point was development of RA (by ACR criteria) at year 1. Patients were monitored by radiography, MRI, CCP2, rheumatoid factor and 28 joint count Disease Activity Score (DAS28) over 2 years.

Results: At year 1, 12/26 (46%) abatacept-treated versus 16/24 (67%) placebo-treated patients developed RA (difference (95% CI) -20.5% (-47.4% to 7.8%)). Adjusted mean changes from baseline to year 1 in Genant-modified Sharp radiographic scores for abatacepttreated versus placebo-treated patients, respectively, were 0 versus 1.1 for total score, and 0 versus 0.9 for erosion score. Mean changes from baseline to year 1 in MRI erosion, osteitis and synovitis scores were 0, 0.2 and 0.2, respectively, versus 5.0, 6.7 and 2.3 in the abatacept versus placebo groups. Safety was comparable between groups; serious adverse events occurred in one patient (3.6%) in each group.

Conclusion: Abatacept delayed progression of UA/very early RA in some patients. An impact on radiographic and MRI inhibition was seen, which was maintained for 6 months after treatment stopped. This suggests that it is possible to alter the progression of RA by modulating T-cell responses at a very early stage of disease. Trial registration number NCT00124449.

Show MeSH
Related in: MedlinePlus