Safety and Efficacy of the Selective Costimulation Modulator Abatacept in Patients with Rheumatoid Arthritis Receiving Background Methotrexate: A 5-year Extended Phase IIB Study

Westhovens, René; Kremer, Joel M.; Moreland, Larry W.; Emery, Paul; Russell, Anthony S.; Li, Tracy; Aranda, Richard; Becker, Jean‐Claude; Qi, Keqin; Dougados, Maxime

doi:10.3899/jrheum.080813

Cited by 114 publications

(88 citation statements)

References 25 publications

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“…In particular, the proportions of patients achieving disease activity targets of DAS28, SDAI, and CDAI remission were maintained through the LTE. Similar longterm outcomes have been reported for patients treated with IV ABA in a similar population of patients with RA and inadequate response to MTX 3,5 . Clinical and functional benefits were maintained longterm during the ACQUIRE study, regardless of whether patients received SC ABA throughout, or switched from IV ABA to SC ABA at the start of the LTE.…”

Section: Rheumatologysupporting

confidence: 77%

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

Genovese

Pacheco‐Tena²,

Covarrubias³

et al. 2014

J Rheumatol

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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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Section: Rheumatologysupporting

confidence: 77%

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

Genovese

Pacheco‐Tena²,

Covarrubias³

et al. 2014

J Rheumatol

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“…The commonest infections (>5% patients) reported in rituximab group were upper respiratory tract infections, nasopharyngitis, urinary tract infections, bronchitis, sinusitis, diarrhoea, influenza and gastroenteritis (16). This SIE rate is similar to data from long-term follow-up with other bDMARDs used in RA (ranging from 3.0 to 5.2/100 patientyears) (17)(18)(19).…”

Section: Associated-infection and Serious Infection Events (Sie)supporting

confidence: 82%

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use

2015

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The development of B cell-targeted biologics represents a major advance in the treatment of autoimmune rheumatic diseases. As with other immunosuppressive agents, risk of infection is a key clinical concern. This review summarises safety data from 15 years of experience of rituximab in autoimmune diseases with a particular focus on opportunistic infection and class-specific complications and infection risk. Rarely, cases of progressive multifocal leucoencephalopathy in rituximab-treated patients (5/100 000) have accumulated over time although no proven causal association has yet been shown. With repeat cycles of therapy, hypogammaglobulinaemia has been observed in a larger proportion of patients and is associated with increased risk of serious infections. The infection profile of the newer B celltargeted agent, belimumab in patients with active systemic lupus erythematosus is also discussed. Data from registries are needed to extend insights further and also to evaluate for any impact with the difference in mode of action of belimumab and infection risk in this population.(153 words) 4

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“…Baseline demographics and clinical characteristics. Demographics and clinical characteristics at randomization for patients who entered the LTE have been reported, and were comparable between original treatment groups and similar to patients in the DB period 2,8 . Patients had a mean (SD) age of 50.8 years (12.4) and a disease duration of 8.5 years (7.2).…”

Section: Rheumatologymentioning

confidence: 82%

“…Evidence suggests that improvements in clinical efficacy gained in the short term with ABA in patients with an inadequate response to MTX are sustained with continued longterm treatment, up to 5 years in a phase IIb study, with consistent safety with increasing exposure 5,6,7,8 . Further, persistent inhibition of the progression of structural damage with continued treatment has been observed for up to 3 years 6,9 .…”

mentioning

confidence: 98%

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

Kremer

Peterfy²,

Russell³

et al. 2014

J Rheumatol

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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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Safety and Efficacy of the Selective Costimulation Modulator Abatacept in Patients with Rheumatoid Arthritis Receiving Background Methotrexate: A 5-year Extended Phase IIB Study

Cited by 114 publications

References 25 publications

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

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

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use

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

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