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

Ann Rheum Dis. 2008 Apr;67(4):547-54. doi: 10.1136/ard.2007.074773. Epub 2007 Oct 5.

Abstract

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 approximately 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 (< or = 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Autoimmune Diseases / chemically induced
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoconjugates / adverse effects
  • Immunoconjugates / therapeutic use*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasms / chemically induced
  • Opportunistic Infections / complications
  • Quality of Life
  • Severity of Illness Index
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antirheumatic Agents
  • Immunoconjugates
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha
  • Abatacept

Associated data

  • ClinicalTrials.gov/NCT00124982