Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: To describe safety profile of IV GLM in RA from the Ph3 GLM IV program. AE rates of interest are indirectly compared to those observed in the GLM SC clinical program across rheumatologic indications.
Methods: 2 multicenter, randomized, double-blind, PBO-controlled studies were included in the integrated IV data safety analysis. GO-LIVE evaluated IV PBO or GLM 2mg/kg or 4mg/kg, ± MTX q12wks in pts with active RA despite MTX. GO-FURTHER is evaluating GLM 2mg/kg IV at wks 0, 4, and q8wks +MTX in active RA despite MTX. In the SC GLM program (GO-FORWARD, GO-BEFORE, GO-AFTER [RA], GO-REVEAL [PsA], GO-RAISE [AS]), PBO or GLM (50mg/100mg) was administered SC q4wks in Ph3 studies and q2 or 4 wks in Ph2 study. Approx. half of pts received MTX. Safety findings for the Ph3 GLM IV RA studies combined through the IV dosing period of GO-LIVE (median 60wks exposure) and through the August 15, 2012 cut-off for GO-FURTHER (median 92wks exposure) are reported; for the ongoing SC studies the data cut was through wk160. Comparison of targeted safety events between IV and SC GLM are reported. Pts who received ≥1administration were analyzed.
Results: 1210 pts were treated with IV GLM in the integrated Ph3 RA IV studies with median duration of follow-up of 72.7 wks. Overall AEs observed in the integrated Ph3 RA IV program are summarized(Table). Since follow-up was longer for the SC rheumatology program, more overall events were observed; however when corrected for events/100 pt yrs, no difference in AE rates or significant SAEs were observed between GLM IV and SC. Incidence of non-serious infusion reactions (median 30 minute infusions) remained low regardless of infusion length, and no serious infusion reactions, requiring study discontinuation, were reported. NMSC (incidence/100 pt-yrs of f/u: 0.49 [95%CI: 0.33,0.71] vs 0.14[95% CI: 0.03,0.42] for GLM SC vs GLM IV) and lymphoma rates were numerically higher in the GLM SC grp vs. the GLM IV grp.
Conclusion: Overall safety of IV GLM in RA pts observed through Aug 15, 2012 continue to demonstrate an acceptable safety profile. Rates for events of interest such as malignancies and serious infections in the IV studies are comparable with or lower than rates in the SC studies in RA pts, AS, and PsA.Follow-up through 2yrs will provide information regarding long-term safety of IV GLM.
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Overall AE summary: Phase 3 GLM IV RA studies combined through 120 day safety update |
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|
|
PBO |
GLM |
|
Pts treated/ Avg duration of f/u (wks) |
326/22.3 |
1210*/74.0 |
|
AE/Serious AE/ D/c due to AE |
58.6% /4.0%/1.8% |
82.2%/16.3%//7.2% |
|
Overall infection/Serious infection |
29.8% / 0.9% |
51.3% / 5.8% |
|
Infusion reactions |
2.5% |
4.5% |
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AEs of interest in pts receiving IV or SC GLM: Incidence per 100 pt-years of follow-up (95% CI) |
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|
|
Integrated RA GLM IV studiesa (n= 1213)* |
Rheumatologic GLM SC studiesb(n=2363) |
|
Total pt/yrs of follow-up |
2103 |
5714 |
|
Deaths |
0.62 (0.33, 1.06) |
0.37(0.23, 0.56) |
|
Sepsis |
0.38 (0.16, 0.75) |
0.37 (0.23, 0.56) |
|
Tuberculosis |
0.29 (0.10, 0.62) |
0.32 (0.19, 0.50) |
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Opportunistic Infections |
0.33 (0.13, 0.69) |
0.25 (0.13, 0.41) |
|
Cellulitis |
2.76 (2.09, 3.57) |
2.24 (1.87, 2.66) |
|
Postbaseline ALT ↑ (>1to<3xULN ) |
83.84 (79.97, 87.85) |
85.82 (83.44, 88.26) |
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Lymphoma: Total pt yrs f/u |
2103 |
5713 |
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Observed # of pts with event / Incidence/100pt yrs (95% CI) |
0/0.00 (0.00, 0.14) |
7/0.12 (0.05, 0.25) |
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Other malignancies: Total pt yrs f/u |
2101 |
5707 |
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Observed # of pts with event/ Incidence/100pt yrs(95% CI) |
9/0.48 (0.23, 0.88) |
32/0.56 (0.38, 0.79) |
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All malignancies: Total pt yrs of f/u |
2101 |
5706 |
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Observed # of pts with event/ Expected #of pts with event/ SIR (95% CI) |
9/12.81/0.70 (0.32, 1.33) |
39/33.04/1.18 (0.84, 1.61) |
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aBased on data cut off as of Aug 15, 2012; includes Phase 3 studies of IV GLM in RA pts: GO-LIVE(n=643), GO-FURTHER (n=592).bIncludes C0524T02 (completed Ph2 PK study of SC GLM). Through Wk 160 for ongoing Phase 3 SC studies in rheumatologic indications: (RA: GO-FORWARD, GO-BEFORE, GO-AFTER, PsA: GO-REVEAL, AS: GO-RAISE); *3 PBO+MTX pts in GO-LIVE did not receive IV GLM during the double-blinded phase of the study, but received SC GLM during the LTE of the study. |
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Disclosure:
R. Westhovens,
BMS,
8,
Janssen; Galapagos,
9,
Roche Pharmaceuticals,
2;
C. O. Bingham III,
Janssen Pharmaceutica Product, L.P.,
2,
Janssen Pharmaceutica Product, L.P.,
5,
UCB ,
2,
UCB,
5,
Pfizer,
2,
Pfizer Inc,
5,
AbbVie/Abbott,
5,
Amgen,
5,
BMS,
2,
BMS,
5,
Celgene,
5,
Corrona,
2,
Genetech/Roche,
2,
Genetech/rRoche,
5,
Novartis Pharmaceutical Corporation,
5,
Mesoblast,
2;
M. E. Weinblatt,
Janssen Research & Development, LLC.,
5;
R. Fleischmann,
Genetech Inc, Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas, AstraZeneca, Janssen,
2,
Roche, Abbott, Amgen, UCB Pharma, Pfizer, BMS, Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas, AstraZeneca, Janssen, HGS,
5;
E. C. 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,
Amgen, AstraZeneca, Bristol-Myers Squibb Canada, F-Hoffman-LaRoche, Janssen, Pfizer, UCB,
8;
E. C. Hsia,
Janssen Research & Develpment, LLC.,
3;
B. Hsu,
Janssen Research & Development, LLC.,
3;
L. Kim,
Janssen Research & Development, LLC.,
3;
S. Mudivarthy,
Janssen Research & Development, LLC.,
3;
M. Mack,
Janssen Research & Development, LLC.,
3;
N. Goldstein,
Janssen Research & Development, LLC.,
3;
J. Braun,
Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Chugai, EBEWE Pharma, Janssen, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis and UCB.,
9;
A. Kavanaugh,
Janssen Research & Development, LLC.,
9;
A. M. Mendelsohn,
Janssen Research & Development, LLC.,
3;
J. Kay,
Ardea Biosciences, Eli Lilly, Fidia Farmacutici, SpA, Pfizer, Roche, Sanofi-Aventis,
2,
Amgen, Baxter Healthcare Corporation, BMS, Celgene, fourteen22 Inc., Genentech, Hospira, Inc., Horizon Pharma, Inc., Janssen, Medac Pharma Inc., PanGenetics, B.V., Pfizer, Roche, Savient Pharmaceuticals, Inc., Sun Pharmaceutical Industries Ltd., UCB, ,
5.
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