Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The safety and efficacy of subcutaneous golimumab (GLM)+/-MTX has been evaluated through 2yrs in a phase 3 trial (GO-FORWARD) of pts with active rheumatoid arthritis (RA) despite MTX therapy. Final safety and efficacy results through 5yrs are reported.
Methods: Pts in GO-FORWARD were randomized to placebo(PBO)+MTX, GLM 100mg+PBO, GLM 50mg+MTX, or GLM 100mg+MTX q4w. PBO+MTX pts crossed over to GLM+MTX at wks 16 (blinded early escape) or 24 (crossover). Pts continued treatment at wk52 (start of long-term extension). After the last pt completed wk52 and unblinding occurred, MTX and corticosteroid use could be adjusted, and a one-time GLM dose increase (50 à100mg) or decrease (100 à50mg) was permitted based on investigator judgment. The last GLM injection was at wk252. Observed efficacy results (ACR20/50/70, DAS28-CRP, HAQ-DI, radiographic) by randomized treatment group and cumulative safety data are reported through wks 256 and 268, respectively.
Results: A total of 444 pts were randomized; 313 pts continued treatment through wk252, and 131 pts withdrew (64 for AE, 25 for lack of efficacy, 1 protocol violation, 6 lost to follow-up, 32 for other reasons, 3 deaths). 301 completed the safety follow-up through wk268. Efficacy results are presented in the table. At wk256, 76.0% of all pts had an ACR20, 89.5% had a DAS28-CRP EULAR response, and 68.5% had improvement in HAQ-DI ≥0.25. Changes from baseline in mean total vdH-S scores were small; 54% of pts randomized to GLM+MTX had no radiographic progression (DvdH-S≤0). The most common AEs were upper respiratory tract infection (32.9%), nasopharyngitis (17.1%), and bronchitis (17.1%); 9.2% of pts had an injection-site reaction. Through wk268, 172/434 pts (39.6%) had an SAE; 14.1% of pts discontinued study agent due to AEs. The rates of serious infections, malignancies, and death were 11.5%, 6.2%, and 1.8%, respectively. Of 429 pts with available samples, 33 (7.7%) were positive for antibodies to GLM.
Conclusion: The retention rate was high (70.5%), and improvements in signs/symptoms of RA and in physical function with GLM+MTX therapy were maintained long-term. Radiographic progression appeared controlled with small changes in mean vdH-S scores observed through 5yrs. The long-term safety of GLM is consistent with other anti-TNFα agents.
Table. Efficacy results at wk256
|
Efficacy at wk256 |
PBO+MTXa |
GLM100mg +PBOb |
GLM 50mg +MTXb |
GLM 100mg +MTXb |
Total |
|
|
ACR20 |
69/91 (75.8%) |
71/93 (76.3%) |
57/74 (77.0%) |
44/59 (74.6%) |
241/317 (76.0%) |
|
|
ACR50 |
43/91 (47.3%) |
48/93 (51.6%) |
40/74 (54.1%) |
28/59 (47.5%) |
159/317 (50.2%) |
|
|
ACR70 |
21/91 (23.1%) |
27/93 (29.0%) |
28/74 (37.8%) |
15/59 (25.4%) |
91/317 (28.7%) |
|
|
DAS28-CRP EULAR Response |
81/90 (90.0%) |
83/92 (90.2%) |
65/73 (89.0%) |
52/59 (88.1%) |
281/314 (89.5%) |
|
|
DAS28-CRP Remission (<2.6) |
38/90 (42.2%) |
41/92 (44.6%) |
35/73 (47.9%) |
27/59 (45.8%) |
141/314 (44.9%) |
|
|
SDAI ≤3.3 |
25/90 (27.8%) |
21/92 (22.8%) |
20/73 (27.4%) |
17/60 (28.3%) |
83/315 (26.3%) |
|
|
DAS28-CRP ≤3.2 |
56/90 (62.2%) |
59/92 (64.1%) |
46/73 (63.0%) |
38/60 (63.3%) |
199/315 (63.2%) |
|
|
HAQ-DI improvement ≥0.25 |
61/91 (67.0%) |
59/93 (63.4%) |
55/74 (74.3%) |
42/59 (71.2%) |
217/317 (68.5%) |
|
|
Radiographic results at wk256. |
||||||
|
Estimated annual progression rate at baselinec |
5.3 ± 7.8 |
5.6 ± 8.9 |
4.7 ± 6.9 |
5.4 ± 13.7 |
5.3 ± 9.3 |
|
|
Mean ± SD annual rate of progression through 5yrsd |
0.7 ± 2.0 |
1.0 ± 2.3 |
0.3 ± 1.2 |
0.7 ± 2.2 |
0.7 ± 2.0 |
|
|
Mean ± SD change in vdH-S score |
3.2 ± 9.2 |
4.6 ± 10.9 |
1.7 ± 6.1 |
3.3 ± 10.2 |
3.3 ± 9.4 |
|
|
Change in vdH-S score ≤0 |
52/95 (54.7%) |
43/99 (43.4%) |
47/79 (59.5%) |
30/65 (46.2%) |
172/338 (50.9%) |
|
|
aPts switched to GLM at wk16 or 24. bAfter wk52 pts could receive GLM50 mg or 100mg, and MTX could be added/adjusted. c vdH-S score divided by the disease duration per pt. dChange in vdH-S score divided by GLM treatment duration per pt. |
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Disclosure:
E. Keystone,
Abbott, Amgen, AstraZeneca, Baylis Medical, Bristol-Myers Squibb, F-Hoffman-LaRoche, Janssen, Lilly Pharmaceuticals, Novartis, Pfizer, Sanofi-Aventis, UCB,
2,
Abbott, AstraZeneca, Baylis Medical, Biotest, Bristol-Myers Squibb, F-Hoffman-LaRoche, Genentech, Janssen, Lilly Pharmaceuticals, Merck, Nycomed, Pfizer, UCB,
5,
Abbott, Amgen, AstraZeneca, Bristol-Myers Squibb Canada, F-Hoffman-LaRoche, Janssen, Pfizer, UCB,
8;
M. C. Genovese,
Janssen Research & Development, LLC.,
2,
Janssen Research & Development, LLC.,
5;
S. Hall,
Janssen Research & Development, LLC.,
9;
P. Miranda,
Janssen, HGS, Medimmune,Celltrion, Sanofi, Roche, Pfizer, and MSD,
9,
Pfizer Inc,
9;
S. C. Bae,
Janssen Research & Development, LLC.,
9;
C. Han,
Janssen Global Services, LLC.,
3;
T. A. Gathany,
Janssen Global Services, LLC,
3;
Y. Zhou,
Janssen Research & Development, LLC.,
3;
S. Xu,
Janssen Research & Development, LLC.,
3;
E. C. Hsia,
Janssen Research & Develpment, LLC.,
3.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/final-5-year-safety-and-efficacy-results-of-a-phase-3-randomized-placebo-controlled-trial-of-golimumab-in-patients-with-active-rheumatoid-arthritis-despite-prior-treatment-with-methotrexate/