1233 - Safety and Efficacy of Etanercept Over Five Years in a Large, UK Observational Cohort

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
C. D. Poole1, Paul Emery2, Adam Young3, Duncan Porter4, C. L. Morgan1, H. Walker5, C. J. Currie6 and A. Reynolds7, 1Pharmatelligence, Cardiff, United Kingdom, 2Chapel Allerton Hospital, Leeds, United Kingdom, 3City Hospital, St Albans, United Kingdom, 4Gartnavel General Hosp, Glasgow, United Kingdom, 5Pfizer UK Ltd, Tadworth, United Kingdom, 6Cardiff University, Cardiff, United Kingdom, 7Reynolds Clinical Sciences Ltd, Eastleigh, United Kingdom
Presentation Number: 1233

Background/Purpose:

Prospective observational registries have been established to monitor the long-term safety of TNF inhibitors and standard disease modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). The purpose of this study was to evaluate relative safety of etanercept (ETN) when compared with a DMARD reference cohort and the efficacy of ETN over 5 years using data from a UK registry.

Method:

The British Society of Rheumatology Biologics Register (BSRBR) provided anonymised raw data on ETN and DMARD cohorts. No further data was provided if a patient switched to a non-ETN biologic. At baseline, patients underwent detailed clinical assessment by a rheumatologist. Follow-up questionnaires were completed every six months for three years by consultants and patients, then annually by consultants only for two more years. Health Assessment Questionnaire (HAQ) data were characterized for the first three years.

Patients with a potential for five years follow-up, a maximum window of 90 days between RA treatment initiation and baseline registration were included. HAQ changes and DAS28 remission rates were calculated. Survival rates for serious adverse events were examined using Kaplan-Meier survival models and risk differences compared using the multivariate Cox proportional hazards model. These models were specified using a forward manual inclusion method for parameters where P<0.05. Subjects were followed to the date of last follow-up or death.

Result:

ETN n=3,470, DMARDs n=1,365. Mean (median) follow-up 4.1 (4.9) years in both groups. Adjusted hazard ratios (aHR) for ETN vs. DMARDs and efficacy outcomes for ETN are detailed in Table 1. There were statistically significant differences in aHRs for malignancy and cardiovascular events. Of note was a significant reduction in mortality observed when deaths were restricted to on drug+90days with ETN aHR = 0.512 (95% CI 0.3800.690, p<0.001), although this was not significant over the full observation period. Concomitant methotrexate therapy was associated with an increased likelihood of remission vs. ETN monotherapy (odds ratio [OR] = 1.69 (95%CI 1.32-2.14, p<0.001) at one year, and OR = 1.47 (95%CI 1.12-1.93, p=0.006) at five years). Subjects treated with ETN showed a significant improvement in HAQ compared with those receiving DMARDs at each timepoint during the first three years: -0.283 vs. -0.013 at 1yr; -0.305 vs. +0.008 at 2yrs, -0.272 vs. +0.101 at 3yrs (all p<0.001).

Conclusion:

This evaluation at 5 years showed that ETN therapy was effective, whilst not associated with any increased risk of serious infection, malignancy, cardiovascular events or death when compared to a DMARD reference group; some risks may be reduced. While residual confounding may exist, this real-world data showed treatment with ETN was effective and as safe as treatment with DMARDs in patients with RA.

Table 1

aHR ETN vs DMARDs for safety outcomes

Safety parameters

aHR

95% CI

p-value

Serious infection

1.01

0.81-1.26

0.943

Malignancy

0.74

0.58-0.96

0.023

Lymphoproliferative malignancy

0.64

0.30-1.40

0.266

Cardiovascular events

0.64

0.49-0.85

0.002

Death

0.80

0.62-1.04

0.096

Efficacy outcomes for ETN

Year

1

2

3

4

5

% patients remaining on ETN

71

61

54

49

40

% patients in remission (DAS28<2.6)

16

18

18

19

19


Keywords: anti-TNF therapy, etanercept, rheumatoid arthritis (RA) and rheumatoid arthritis, treatment

Disclosure: C. D. Poole, Pfizer Inc, 5 ; P. Emery, Expert advice Pfizer/Merck/Abbott/BMS/Roche, 5 ; A. Young, Pfizer Inc, 5 ; D. Porter, Pfizer Inc, 5, UCB, 5, MSD, 5, Pfizer Inc, 2, Abbott Laboratories, 2, Roche Pharmaceuticals, 2, Abbott Laboratories, 8 ; C. L. Morgan, Pfizer Inc, 5 ; H. Walker, Pfizer Inc, 3 ; C. J. Currie, Pfizer Inc, 5 ; A. Reynolds, Pfizer Inc, 5, Napp, 5, Pfizer Inc, 1 .