Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Benefit of Continuing Treatment Beyond 12 Weeks in Patients with Rheumatoid Arthritis Treated with Tocilizumab and DMARDs Who Had Previous Inadequate Responses to DMARDs or TNF Inhibitors
Keystone1, Edward C., John2, A., Wong3, K.
Professor of Medicine/University of Toronto, Toronto, ON
Roche, Nutley, NJ
Everest Clinical Research Services Inc, Markham, ON
Purpose:
Some patients (pts) with rheumatoid arthritis (RA) achieve rapid responses to treatment with biologic agents, but those who do not respond early may still reach clinical responses if treatment is continued. The objective of this post hoc analysis was to assess the midterm course of pts with no or limited responses to treatment with tocilizumab (TCZ) and DMARDs, including methotrexate (MTX), at wk 12.
Method:
This analysis was performed using data from pts who participated in 4 phase 3 clinical trials and who had previous inadequate responses to DMARDs (DMARD-IR; pooled data from OPTION, TOWARD, and LITHE) or tumor necrosis factor-a inhibitors (TNFi-IR, RADIATE). Pts were treated for 24 wks with TCZ (4 mg/kg or 8 mg/kg) and DMARDs/MTX. Proportions of nonresponders (NR) in various disease activity parameters (ACR20/50/70, LDAS [DAS28 <=3.2], DAS28 remission [<2.6]) at wk 12 but who achieved the respective responses at wk 24 (responders [R]) were determined.
Results:
The analysis included 2018 DMARD-IR pts and 331 TNFi-IR pts (Table). Response rates at wk 12 for ACR20/50/70, LDAS, and DAS28 remission were numerically higher for pts in the DMARD-IR and TNFi-IR populations who were randomly assigned to TCZ 8 mg/kg than to TCZ 4 mg/kg. Of DMARD-IR pts, more in the TCZ 8 mg/kg (33%) than in the TCZ 4 mg/kg (25%) group who were ACR20 NR at wk 12 responded by wk 24. Similarly, of TNFi-IR pts, more in the TCZ 8 mg/kg (27%) than the TCZ 4 mg/kg (10%) group who were ACR20 NR at wk 12 responded by wk 24. High-level responses became more apparent after 24 wks of TCZ treatment for pts who had not achieved the respective level of responses at wk 12, with absolute response rates numerically higher for pts in the TCZ 8 mg/kg group than in the TCZ 4 mg/kg group.
| DMARD-IR n = 2018 | TNFi-IR n = 331 | |||
|---|---|---|---|---|
| TCZ 8mg/kg + DMARDs/MTX n = 1406 | TCZ 4mg/kg + MTX n = 612 | TCZ 8mg/kg + MTX n = 170 | TCZ 4mg/kg + MTX n = 161 | |
| Week 12 responders, % | ||||
| ACR20/50/70 | 55/27/11 | 51/23/8 | 44/23/8 | 39/14/2 |
| LDAS/DAS28 remission | 33/22 | 18/8 | 26/14 | 8/3 |
| Week 12 nonresponders who were responders at week 24% (n/n) | ||||
| ACR20 NR to ACR20 | 33 (213/637) | 25 (73/297) | 27 (26/96) | 10 (10/98) |
| ACR 50 NR to ACR50 | 23 (238/1021) | 16 (74/470) | 15 (20/131) | 11 (15/139) |
| ACR 70 NR to ACR70 | 13 (157/1246) | 7 (42/562) | 6 (10/156) | 4 (7/157) |
| LDAS NR to LDAS | 26 (229/883) | 17 (81/476) | 29 (31/107) | 7 (9/131) |
| DAS28 NR to DAS28 | 17 (177/1020) | 9 (48/532) | 19 (24/124) | 2 (3/139) |
| Week 24 responders who were nonresponders at week 12, % (n/n) | ||||
| ACR20 NR to ACR20 | 26 (213/832) | 24 (73/304) | 31 (26/85) | 20 (10/49) |
| ACR 50 NR to ACR50 | 46 (238/520) | 44 (74/167) | 41 (20/49) | 56 (15/27) |
| ACR 70 NR to ACR70 | 60 (157/260) | 60 (42/70) | 48 (10/21) | 88 (7/8) |
| LDAS NR to LDAS | 42 (229/547) | 57 (81/143) | 52 (31/60) | 64 (9/14) |
| DAS28 NR to DAS28 | 50 (177/357) | 65 (48/74) | 69 (24/35) | 50 (3/6) |
Conclusion:
Results of this analysis indicated that substantial proportions of DMARD-IR and TNFi-IR pts who do not respond to 12 wks of treatment with TCZ and DMARDs achieve responses if treatment is continued for 24 wks. In the more difficult to treat TNFi-IR population, nearly 30% of pts who do not achieve ACR20 or LDAS after 12 wks of treatment with TCZ 8 mg/kg and DMARDs will reach the respective responses by wk 24 if treatment is continued. Clinicians should be aware that some pts require more than 12 wks of TCZ treatment to achieve clinical benefit.
To cite this abstract, please use the following information:
Keystone, Edward C., John, A., Wong, K.; Benefit of Continuing Treatment Beyond 12 Weeks in Patients with Rheumatoid Arthritis Treated with Tocilizumab and DMARDs Who Had Previous Inadequate Responses to DMARDs or TNF Inhibitors [abstract]. Arthritis Rheum 2009;60 Suppl 10 :410
DOI: 10.1002/art.25493
