ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2318

Disease Activity in Moderate and Severe Rheumatoid Arthritis At Discontinuation in 10-Year Open-Label Extension Studies With Etanercept

Michael E. Weinblatt1, Joan M. Bathon2, Michele Hooper3, Bojena Bitman4, Yue Yang5, David H. Collier6, James Chung7 and Mark C. Genovese8, 1Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 2Columbia University, New York, NY, 3Amgen Global Safety, Amgen Inc., Thousand Oaks, CA, 4Amgen, Inc., San Francisco, CA, 5Assent Consulting, South San Francisco, CA, 6Amgen Inc., Thousand Oaks, CA, 7Amgen, Thousand Oaks, CA, 8Division of Rheumatology, Stanford University, Palo Alto, CA

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy III

Session Type: Abstract Submissions (ACR)

Background/Purpose:   Retention rates may be used as a surrogate of long-term effectiveness of drug therapy in open-label studies.  Studies have reported that patients (pts) with moderate rheumatoid arthritis (RA) are more likely to achieve low disease activity or remission than pts with severe disease.  We examined disease activity in pts who withdrew from long-term open-label extension (OLE) studies of etanercept (ETN) for reasons other than loss of efficacy (LOE) to see if they had lost drug response and whether response rates differed by baseline disease activity.

Methods:   Data from pts with early RA (ERA) and long-standing RA (LRA) enrolled in OLE studies were analyzed.  Using disease activity score with 28 joint count with CRP (DAS28-CRP) criteria, pts were categorized at baseline of the original study as having moderate (DAS28-CRP ≥3.2 and ≤5.1) or severe (DAS28-CRP >5.1) disease.  In the original studies, ERA pts received methotrexate (MTX) or ETN monotherapy and LRA pts received ETN, MTX, ETN+MTX, or placebo.  All pts received ETN in the OLE studies.  For this analysis, DAS28-CRP was evaluated at the time of first efficacy measurement after patients initiated ETN (either parent study or OLE) as baseline and at study withdrawal.  We compared DAS28-CRP in moderate and severe pts who had withdrawn for LOE or other reasons with pts who completed the OLE studies.

Results:   Overall, 65.2% of ERA pts and 69.6% of LRA pts withdrew over the 10 years of the OLE studies.  More pts withdrew for reasons other than LOE as listed by the investigator.  Pts who withdrew for LOE showed no improvement in DAS28-CRP from baseline until last DAS28-CRP measurement (Table).  Pts who withdrew for other reasons (eg, physician decision, protocol issues, patient refusal, others) had improved DAS28-CRP from baseline, but not as low as pts who completed the study.  While DAS28-CRP scores in pts who withdrew for LOE were similar between moderate and severe pt groups, mean DAS28-CRP was lower in pts with moderate RA compared with pts with severe RA in both ERA and LRA pts at the time of withdrawal for reasons other than LOE and in the completer group.

Conclusion:   ERA and LRA pts with moderate or severe disease who withdrew from ETN OLE studies for reasons other than LOE (the majority of pts) had a positive clinical response at the time of withdrawal so the overall withdrawal rate did not reflect lack of drug efficacy.  Pts who withdraw from long-term studies for reasons other than LOE generally still demonstrate improvement over their baseline DAS28-CRP.  Also, while ETN treatment is effective in ERA and LRA pts with moderate and severe disease, pts with moderate disease at baseline achieved lower DAS 28-scores than pts with severe disease.

 

Baseline and Last DAS28-CRP in Patients who Withdrew and Patients who Continued in Etanercept Clinical Trials by Withdrawal Category

 

Moderate RA

Severe RA

 

n

Mean (SD)

n

Mean (SD)

ERA Patients

 

 

 

 

MTX in original study, ETN in OLE

 

 

 

 

  Withdrew for LOE
     Baseline DAS28-CRP
     Last DAS28-CRP

4
4

4.81 (1.73)
5.97 (0.98)

7
7

4.48 (0.49)
5.84 (1.14)

  Withdrew for other reason (not AE)
     Baseline DAS28-CRP
     Last DAS28-CRP

13
13

3.50 (1.50)
2.97 (0.91)

47
44

4.39 (1.38)
4.02 (1.64)

  Continued to study closure
     Baseline DAS28-CRP
     Last DAS28-CRP

10
10

3.52 (1.72)
2.55 (1.46)

42
42

3.69 (1.37)
2.73 (1.03)

ETN in original study, ETN in OLE

 

 

 

 

  Withdrew for LOE
     Baseline DAS28
     Last DAS28

6
5

4.63 (0.30)
5.15 (1.70)

29
29

6.37 (0.68)
5.63 (1.52)

  Withdrew for other reason (not AE)
     Baseline DAS28
     Last DAS28

34
34

4.50 (0.51)
3.27 (1.43)

118
118

6.45 (0.78)
3.80 (1.50)

  Continued to study closure
     Baseline DAS28-CRP
     Last DAS28-CRP

32
31

4.41 (0.46)
2.50 (1.02)

109
108

6.30 (0.74)
2.79 (1.13)

LRA Patients

 

 

 

 

  Withdrew for LOE
     Baseline DAS28
     Last DAS28

8
8

4.61 (0.37)
4.99 (1.30)

69
69

6.66 (0.72)
5.71 (1.27)

  Withdrew for other reason (not AE)
     Baseline DAS28-CRP
     Last DAS28-CRP

35
34

4.59 (0.40)
3.25 (1.35)

143
141

6.55 (0.79)
4.58 (1.44)

  Continued to study closure
     Baseline DAS28-CRP
     Last DAS28-CRP

42
41

4.20 (0.98)
2.51 (1.12)

151
149

5.57 (1.51)
2.77 (1.10)

ERA, early rheumatoid arthritis; LRA, long-standing rheumatoid arthritis; LOE, lack of efficacy; DAS28-CRP, Disease Activity Score using 28 joint count with CRP; AE, adverse events

Funded by Immunex, a wholly owned subsidiary of Amgen Inc. and by Wyeth.

Disclosure:

M. E. Weinblatt,

Amgen,

5;

J. M. Bathon,
None;

M. Hooper,

Amgen,

3,

Amgen,

1;

B. Bitman,

Amgen Inc.,

1,

Amgen Inc.,

3;

Y. Yang,

Amgen Inc.,

9;

D. H. Collier,

Amgen Inc.,

1,

Amgen Inc.,

3;

J. Chung,

Amgen ,

1,

Amgen,

3;

M. C. Genovese,

Amgen,

2,

Amgen,

5.

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