Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: To present an analysis of pooled data through approx 5yrs of follow-up from 5 completed golimumab(GLM) Ph3 SC trials across rheumatological indications.
Methods: SC placebo (PBO) or GLM (50mg or100mg) was administered q4wks in Ph3 trials. After wk24/52, pts in the Ph3 studies entered LTE and received GLM50mg or 100mg q4wks in an unblinded fashion. Dose adjustment from 50mg to 100mg and 100mg to 50mg was allowed once. Concomitant meds included DMARDs (mostly MTX). AEs were analyzed based on treatment received by a pt during the course of the study; PBO, 50mg only, 100mg only, or 50mg and 100mg. Because pts could cross-over from PBO to GLM, a pt may appear in both PBO and GLM columns. Due to the short duration of the PBO-controlled portion, comparisons between GLM and PBO grps are limited.
Results: In Ph3 trials, 639pts received PBO, 671 GLM50mg, 765 GLM50mg and GLM100mg, and 792 GLM100mg through 5yrs. In Ph3, 5.2%, 15.4%, 9.5% and 19.9% of PBO, GLM50 only, GLM50 and GLM100mg, and GLM100mg only pts, respectively, discontinued due to AE through 5yrs. The incidences per 100PY of deaths, serious infections (including TB,opportunistic infections [OI]), demyelination, and malignancies are presented. Injection site reactions were low; most were mild, and 2 cases led to discontinuation. No GLM SC-treated pt developed anaphylaxis/serum sickness-like reaction. Malignancies occurring during the 5 Ph3 trials included skin cancers, solid tumors, and lymphoma. In comparison to SEER, overall incidence of malignancies in GLM-and PBO-treated pts was similar to that expected in the general US population. Incidence of lymphomas per 100 pt-years of follow-up was greater in the GLM100mg dose grp through 5yrs and higher than that expected in the general US population.
Conclusion: The safety of continued SC GLM exposure demonstrates that GLM was generally well-tolerated with overall low rates of discontinuation due to AEs. Safety profiles were generally similar between GLM dose with exception of higher rates of serious infections, including TB and opportunistic infections, and lymphoma in the GLM100mg grp. Results are confounded by LTE design in which pts could receive GLM100mg after being exposed to GLM50mg with higher GLM dose used for pts with more refractory disease and by limited exposure to PBO making the comparisons between PBO and treatment grps of less value.
|
|
PBO +/- MTX |
GLM50mg +/- MTX |
GLM50mg and GLM100mg +/- MTX |
GLM100mg +/- MTX |
|
Pts treated (n) |
639 |
671 |
765 |
792 |
|
Total pt/yrs of follow-up |
350 |
2375 |
3346 |
2983 |
|
Deaths |
0.29(0.01, 1.59) |
0.46(0.23, 0.83) |
0.27(0.12, 0.51) |
0.54(0.31, 0.87) |
|
All serious infections |
4.86(2.83, 7.78) |
2.48(1.89, 3.20) |
3.26(2.67, 3.93) |
3.96(3.27, 4.74) |
|
Tuberculosis (TB) |
0.00(0.00, 0.86) |
0.17(0.05, 0.43) |
0.21(0.08, 0.43) |
0.30(0.14, 0.57) |
|
Opportunistic infections(not TB) |
0.00(0.00, 0.86) |
0.13(0.03, 0.37) |
0.12(0.03, 0.31) |
0.34(0.16, 0.62) |
|
Demyelination* |
||||
|
Total pt/yrs of follow-up |
350 |
2375 |
3346 |
2979 |
|
Incidence/100 pt yrs( 95%CI) |
0.00(0.00, 0.86) |
0.00(0.00, 0.13) |
0.03(0.00, 0.17) |
0.20(0.07, 0.44) |
|
Malignancy |
||||
|
Nonmelanoma skin cancers (NMSC) |
||||
|
Total pt/yrs of follow-up |
347 |
2371 |
3319 |
2947 |
|
Observed # of pts with event |
6 |
6 |
16 |
15 |
|
Incidence/100 pt yrs (95%CI) |
1.73(0.63,3.76) |
0.25(0.09,0.55) |
0.48(0.28,0.78) |
0.51(0.28,0.84) |
|
Lymphoma |
||||
|
Total pt/yrs of follow-up |
350 |
2374 |
3346 |
2982 |
|
Observed # of pts with event |
0 |
1 |
2 |
6 |
|
Incidence/100 pt yrs (95% CI) |
0.00(0.00,0.86) |
0.04(0.00,0.23) |
0.06(0.01, 0.22) |
0.20(0.07,0.44) |
|
Expected # of pts with event |
0.09 |
0.59 |
0.95 |
0.78 |
|
SIR (95% CI) |
0.00(0.00,33.23) |
1.71(0.04,9.50) |
2.11(0.26, 7.61) |
7.71(2.83, 16.78) |
|
Other malignancies |
||||
|
Total pt/yrs of follow-up |
349 |
2369 |
3345 |
2977 |
|
Observed # of pts with event |
3 |
20 |
11 |
17 |
|
Incidence/100 pt yrs (95% CI) |
0.86(0.18,2.51) |
0.84(0.52,1.30) |
0.33(0.16, 0.59) |
0.57(0.33, 0.91) |
|
Expected # of pts with event |
1.98 |
12.34 |
20.63 |
16.70 |
|
SIR (95% CI) |
1.52(0.31,4.44) |
1.62(0.99,2.50) |
0.53(0.27, 0.95) |
1.02(0.59,1.63) |
|
GLM SC program including 3RA, 1 PsA, 1 AS studies;*Based on data through end of studies (approximately 5 years) |
||||
Disclosure:
J. Kay,
AbbVie Inc., Ardea Biosciences, Inc., Eli Lilly and Company, and Roche Laboratories, Inc.,
2,
AbbVie Inc., Amgen, Inc., AstraZeneca, Bristol Myers Squibb Co., Crescendo BioScience Inc., Epirus Biopharmaceuticals, Inc., Genentech Inc., Hospira, Inc., Janssen Biotech, Inc., PanGenetics, B.V., Pfizer Inc., Roche Laboratories, Inc., and UCB, Inc.,
5;
R. Fleischmann,
AbbVie, Amgen, Ardea, Astra Zeneca, BMS, Celgene, GSK, Janssen, Eli Lilly, Merck, Pfizer, Resolve, Roche, Sanofi Aventis, UCB.,
2,
AbbVie, Akros, Amgen, Antares, Ardea, Astra Zeneca, Augurex, BMS, Celgene, Covagen, Five Prime, GSK, Iroko, Janssen, Eli Lilly, McNeil, Merck, Pfizer, Plexxicon, Resolve, Roche, Sanofi Aventis, Teva, UCB, Vertex. ,
5;
E. C. Keystone,
Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB. ,
2,
Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB. ,
5,
Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, UCB, Amgen.,
8;
E. C. Hsia,
Janssen Research and Development, LLC.,
3;
N. Goldstein,
Janssen Research & Development, LLC.,
3;
B. Hsu,
Janssen Research & Development, LLC.,
3;
Y. Zhou,
Janssen Research & Development, LLC.,
3;
J. Braun,
Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma,
5,
Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma,
2;
A. Kavanaugh,
AbbVie,
2,
Amgen,
2,
Roche Pharmaceuticals,
2,
Pfizer Inc,
2,
Janssen Pharmaceutica Product, L.P.,
2,
UCB,
2,
BMS,
2,
Astellas,
2.
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