Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Long-Term Safety of Abatacept: Integrated Analysis of Clinical Program Data of up to 7 Years of Treatment.

Hochberg7,  Marc C., Westhovens4,  Rene, Aranda2,  Richard, Kelly2,  Sheila M., Khan2,  Nadar, Qi2,  Keqin, Pappu2,  Ramesh

Brigham & Womens Hospital, Boston, MA
Bristol-Myers Squibb, Princeton, NJ
Bristol-Myers Squibb, Braine-l'Alleud, Belgium
Catholic University of Leuven, Leuven, Belgium
Fox Chase Cancer Center, Philadelphia, PA
Univ of Pittsburgh Med Ctr, Pittsburgh, PA
University of Maryland, Baltimore, MD

Background:

Integrated analyses of clinical trial data are important to assess long-term (LT) safety and detect rare events. Here the authors present an integrated analysis of safety data from the abatacept RA clinical trial program up to December 2009, including 12,132 patient–years (p–y) of exposure.

Methods:

Data from eight abatacept RA clinical trials were classified into short-term (ST) and LT periods and analyzed. ST data included six double-blind (6- or 12-month), placebo-controlled periods, one non-randomized Phase II study and one non-randomized Phase III study. The LT data included the open-label (OL) periods of these eight studies. Safety assessments, presented for all patients receiving >=1 dose of abatacept, included adverse events (AEs), serious AEs (SAEs), mortality and events of clinical interest. Incidence rates (IRs) per 100 p–y with 95% CIs were calculated for the ST, LT and cumulative (ST+LT) periods.

Results:

The cumulative period included 4149 patients with 12,132 p–y of exposure; 1165 had >=5 years' exposure. Mean (range) exposure was 35.6 (1.9–104.2) months. The ST period included 3173 patients (2331 p–y) and the LT period included 3256 patients (9752 p–y). IRs for the ST, LT and cumulative periods are presented (Table). Annual IRs (95% CIs) per 100 p–y for SAEs did not increase with increasing abatacept exposure: Year 1, 19.13 (17.67–20.67); Year 2, 14.39 (12.80–16.11); Year 3, 12.82 (11.09–14.74); Year 4, 10.53 (8.76–12.57); Year 5, 10.18 (8.11–12.62); Year 6, 7.09 (4.54–10.55); Year 7, 8.90 (4.74–15.22). During the cumulative period, the IR (95% CI) of hospitalized infection was 2.64 per 100 p–y (2.35–2.95). The IRs (95% CIs) for the most common serious infections were; pneumonia: 0.46 (0.34–0.59); urinary tract infection: 0.20 (0.13–0.30); cellulitis: 0.18 (0.11–0.28). There were few opportunistic infections (0.36 [0.27–0.49]), with only eight cases of tuberculosis (0.07 [0.03–0.13]) observed overall. The IRs (95% CIs) for non-melanoma skin cancer and solid tumors in the cumulative period were 0.73 (0.58–0.90) and 0.59 (0.46–0.75) per 100 p–y, respectively.

Conclusions:

The integrated safety data from 4149 patients with 12,132 p–y of exposure up to 7 years demonstrate that abatacept is generally well tolerated. No new safety events were identified over time, and the types and IRs of safety events (including events of clinical interest) in the LT and cumulative periods were generally consistent with those in the ST period, indicating that the abatacept safety profile remains stable with increasing duration of exposure.

Table. Safety events during the short-term, long-term and cumulative periods

  ST (n = 3173)LT (n = 3256)Cumulative (n = 4149)
P-y exposure 2331975212,132
DeathsPatients with event, n126073
 Incidence rate*0.51 (0.27–0.90)0.62 (0.47–0.79)0.60 (0.47–0.76)
Overall SAEsPatients with event, n40010861373
 Incidence rate*18.15 (16.41–20.02)14.31 (13.47–15.18)14.61 (13.85–15.41)
Serious infections†Patients with event, n85260332
 Incidence rate*3.68 (2.94–4.55)2.79 (2.46–3.15)2.87 (2.57–3.19)
Malignancies (excludingPatients with event, n167288
  NMSC)Incidence rate*0.69 (0.39–1.11)0.74 (0.58–0.93)0.73 (0.58–0.89)
Lung cancerPatients with event, n51318
 Incidence rate*0.21 (0.07–0.50)0.13 (0.07–0.23)0.15 (0.09–0.23)
LymphomaPatients with event, n189
 Incidence rate*0.04 (0.00–0.24)0.08 (0.04–0.16)0.07 (0.03–0.14)
Autoimmune eventsPatients with event, n48NP232
 Incidence rate*2.07 (1.53–2.75)NP1.99 (1.74–2.26)
Acute infusional events‡Patients with event, n225NP377
 Incidence rate*11.61 (10.14–13.22)NP3.90 (3.52–4.32)
*Data show incidence rates per 100 p-y (95% confidence interval); in only six studies ST period, n = 2368, period, n = 3755: ST = short term; LT = long term; SAE = serious adverse event; NMSC = skin cancer; NP = analyses not performed

References:

1Schiff, M, et al. Ann Rheum Dis 2008;67:1096-103

2Genovese, MC, et al. Ann Rheum Dis 2008;67:547-54

3Westhovens, R, et al. Ann Rheum Dis 2009;68:1870-7

To cite this abstract, please use the following information:
Hochberg, Marc C., Westhovens, Rene, Aranda, Richard, Kelly, Sheila M., Khan, Nadar, Qi, Keqin, et al; Long-Term Safety of Abatacept: Integrated Analysis of Clinical Program Data of up to 7 Years of Treatment. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :390
DOI: 10.1002/art.28159

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