Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Anti-TNF therapy in combination with a synthetic DMARD such as methotrexate (MTX) has been extensively shown to be superior to MTX and anti-TNF therapy as monotherapy, and is recommended in patients with rheumatoid arthritis (RA) who failed to reach treatment target, remission or low disease activity (LDA), in particular when poor prognostic markers are present.1 When combined with anti-TNF therapy, MTX is usually administered in doses ranging from 7.5 to 25 mg/week. In patients who develop intolerable side effects to MTX during combination therapy, MTX may be discontinued or its dosage reduced. In clinical studies, the anti-TNF agent etanercept (ETN) has demonstrated sustained efficacy after MTX withdrawal in patients with moderate to severe RA,2 but ETN efficacy across different dosages of concomitant MTX has not been investigated in early to established active RA patients. Based on data pooled from two historic ETN trials (TEMPO3 and COMET4), we evaluated the impact of MTX dosage on clinical, functional, and quality of life (QoL) outcomes in RA patients after 24 months of treatment.
Methods: Patients with active RA in the ETN+MTX combination treatment arms of the TEMPO2 and COMET3studies were stratified into three subgroups based on the MTX dosage at 24 months, having MTX monotherapy groups as control: low dose (L), <10 mg/week; medium dose (M), 10-17.5 mg/week; and high dose (H), >17.5 mg/week. Data from these patient subgroups were included in descriptive summaries of demographic and disease characteristics at baseline; the following outcomes at 24 months were also evaluated for each subgroup: DAS28 LDA and remission; ACR20, 50 and 70 responses; and changes from baseline in DAS28, HAQ-DI, and EQ-5D-VAS.
Results: At baseline, patients in the ETN+MTX arm (n=276; L=73, M=155, H=48), had a mean age of 51.1, 51.7, and 51.7; weight of 69.6 and 70.2, and 75.0 kg; and female gender in 75%, 75% and 69% for the L, M and H dose groups, respectively. Patients in the MTX arm (n=218; L=39, M=117, H=62) had a mean age of 56.1, 50.7, and 51.8; weight of 67.6 and 71.1, and 70.4 kg; and female gender in 79%, 80% and 81% for the L, M and H dose groups, respectively. Responses to ETN+MTX combination therapy at 24 months were consistently high across MTX dosage groups, with very similar rates of LDA/remission (Table). Improvements in DAS28, HAQ-DI, and EQ-5D were also not dependent on MTX dosage in the combination treatment arm; poorer responses and less improvement were observed in the high MTX dose subgroup.
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Table. Clinical, functional, QoL outcomes by MTX dosage in patients in the ETN+MTX and MTX arms across TEMPO and COMET studies3,4 |
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ETN+MTX Arm (n=276) |
MTX Arm (n=218) |
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Low |
Medium MTX Dose |
High |
Low |
Medium MTX Dose |
High |
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% patients achieving endpoint at 24 months (n/N) |
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DAS28 LDA/Remission |
68 (48/71) |
69 (103/149) |
70 (30/43) |
53 (19/36) |
41 (43/106) |
57 (29/51) |
|
ACR20 |
93 (68/73) |
92 (141/153) |
89 (39/44) |
87 (34/39) |
81 (91/112) |
63 (34/54) |
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ACR50 |
79 (58/73) |
78 (120/153) |
73 (32/44) |
64 (25/39) |
55 (62/112) |
46 (25/54) |
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ACR70 |
56 (41/73) |
59 (91/153) |
57 (25/44) |
36 (14/39) |
33 (37/112) |
26 (14/54) |
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Change from baseline to 24 months, mean (SD) |
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DAS28 |
-3.8 (1.2) |
-4.0 (1.2) |
-4.1 (1.5) |
-3.2 (1.3) |
-3.2 (1.5) |
-2.8 (1.7) |
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HAQ-DI |
-1.1 (0.8) |
-1.1 (0.6) |
-1.2 (0.8) |
-0.9 (0.7) |
-0.9 (0.6) |
-0.9 (0.7) |
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EQ-5D VAS |
35.6 (28.7) |
38.0 (26.0) |
32.5 (26.7) |
34.1 (25.9) |
35.3 (27.5) |
19.7 (26.4) |
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DAS28 LDA, Disease Activity Score based on 28-joint count low disease activity (defined as DAS28 ≤3.2); ACR20/50/70, American College of Rheumatology 20%, 50%,and 70% improvement; HAQ-DI, Health Assessment Questionnaire-Disability Index; EQ-5D VAS, EuroQol-5 total index visual analog scale |
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Conclusion: At 24 months, etanercept plus MTX showed similar efficacy outcomes regardless of MTX dosage in patients with RA who participated in the TEMPO2 and COMET3trials.
References: 1. Smolen JS, et al. Ann Rheum Dis 2010;69:964-75. 2. P Van Riel et al Ann Rheum Dis 2006;65;1478-1483 3. Klareskog L, et al. Lancet. 2004;363:675-81. 4. Emery P, et al. Lancet. 2008;372:375-82.
Disclosure:
T. W. J. Huizinga,
TWJ Huizinga has received lecture fees/consultancy fees from Merck, UCB, Bristol Myers Squibb, Biotest AG, Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, Crescendo Bioscience, Nycomed, Boeringher, Takeda, and Eli Lilly,
5;
F. Brock,
Pfizer Inc,
5;
U. Kerkmann,
Pfizer Inc,
1,
Pfizer Inc,
3;
G. Gallo,
Pfizer Inc,
1,
Pfizer Inc,
3.
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