ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 612

Thromboembolic Events Are Not Associated with Anti-Adalimumab Antibodies

Gerd Burmester1, Cem Gabay2, Dilek Arikan3, Anabela Cardoso4, Jasmina Kalabic3, Nathan Pfeifer3, Nupun A. Varothai3, Stefan Florentinus5 and Josef S. Smolen6, 1Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany, 2Rheumatology, Geneva University Hospital, Geneva, Switzerland, 3AbbVie, North Chicago, IL, 4Torre Oriente, AbbVie, Lisboa, Portugal, 5AbbVie Inc., North Chicago, IL, 6Department of Medicine 3, Division of Rheumatology, Medical University Vienna, Vienna, Austria

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ,

Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Treatment of rheumatoid arthritis (RA) with anti-Tumor Necrosis Factor (TNF) such as adalimumab may result in some patients (pts) developing anti-adalimumab antibodies (AAA). Findings from a case control study suggest that occurrence of thromboembolic events is higher in pts treated with adalimumab, who developed AAA, compared to those who did not1.  The objective was to determine if thromboembolic events occur at a higher frequency in pts positive for AAA (AAA+) compared to pts who did not have AAA (AAA-) across several RA clinical trials.

Methods:  This was a post hoc analysis of data from the following clinical trials of adalimumab in pts with RA: DE001, DE004, DE005, DE007, DE009 (ARMADA), DE010, DE011, DE013 (PREMIER), DE019, DE035, DE037, M02-575 (CHANGE), M06-859, M10-261, M12-071 (MUSICA), M12-073 (CONCERTO), and M13-390. Pts with RA who received any adalimumab dose were included in the analysis. The incidence rate of treatment-emergent thromboembolic events which occurred up to the last measurement of AAA, were summarized for AAA+ and AAA- pts as events/ 100 patient years (E/100PY). Preferred terms of the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (17.1) were used to code the events. Arterial events such as transient ischemic attack (TIA), cardiovascular accident (CVA), myocardial infarction (MI), and venous events, such as deep vein thrombosis (DVT) with or without pulmonary embolism, superficial vein thrombosis, and thrombosis at unusual sites were included.

Results: A total of 3995 pts were included; 367 were AAA+ with 276.6 patient years (PY) of adalimumab exposure and 3628 were AAA-, with 2255.7 PY of adalimumab exposure. One out of 367 (0.3%) pts who was AAA+ and 29/3628 (0.8%) pts who were AAA- reported a thromboembolic treatment- emergent adverse event (AE) (Table). In the AAA+ pts, the incidence of AE was 0.4 E/100PY (1 event, a cardiac disorder which did not lead to adalimumab discontinuation). In the AAA- pts, 1.4 E/100PY were reported; <0.1 E/100PY (1 cerebrovascular accident and 1 DVT) led to adalimumab discontinuation. Incidence of serious AEs was 0.4 E/100PY in the AAA+ pts and 0.7 E/PY in the AAA- pts.

Conclusion: Across multiple clinical trials of adalimumab in pts with RA, the incidence rate of embolic and thromboembolic events including DVT was not found to be greater in pts with AAA compared to pts who did not develop these antibodies.

 

Treatment – emergent thromboembolic events occurring up to last AAA measurement date

 

All treatment-emergent thromboembolic events

E (E/100 PY)

Treatment-emergent thromboembolic events leading to discontinuation

E (E/100 PY)

System Organ Class

AAA+

N=367, PY=276.6

AAA-

N=3628, PY=2255.7

AAA+

N=367, PY=276.6

AAA-

N=3628,PY=2255.7

Any adverse event

1 (0.4)

32 (1.4)

0

2 (<0.1)

Cardiac disorders

1 (0.4)

9 (0.4)

–

–

– Acute MI

0

        2 (<0.1)

–

–

–  MI

1 (0.4)

6 (0.3)

–

–

–   Acute coronary syndrome

0

1 (<0.1)

–

 

Nervous system disorders

0

8 (0.4)

–

1 (<0.1)

Vascular disorders

0

15 (0.7)

–

1 (<0.1)

AAA+, pts positive for anti-adalimumab antibody; AAA-, pts negative for anti-adalimumab antibody; E, events; PY, patient years; E/100PY, events per 100 patient years

Reference:

  1. Korswagen et al. Arthritis Rheum, 2011, 63(4):877-83
Disclosure: G. Burmester, Abbvie, 2,Pfizer Inc, 2,UCB, 2,Roche Pharmaceuticals, 2,Abbvie, 5,Bristol-Myers Squibb, 5,Pfizer Inc, 5,Merck Human Health, 5,MedImmune, 5,UCB, 5,Roche Pharmaceuticals, 5,Abbvie, 8,Bristol-Myers Squibb, 8,Pfizer Inc, 8,Merck Human Health, 8,UCB, 8,Roche Pharmaceuticals, 8; C. Gabay, Roche, Pfizer, MSD, AB2 Bio, 2,Roche, Pfizer, MSD, Celgene, AbVie, BMS, Janssen, Debiopharm, AB2 Bio, 5; D. Arikan, AbbVie, 1,AbbVie, 3; A. Cardoso, AbbVie, 9; J. Kalabic, AbbVie, 9; N. Pfeifer, AbbVie, 1,AbbVie, 3; N. A. Varothai, AbbVie, 1; S. Florentinus, AbbVie, 1,AbbVie, 3; J. S. Smolen, AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, 2,Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glaxo, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Novo-Nordisk, Pfizer, Roche, Samsung, Sanofi, UCB, 5.

To cite this abstract in AMA style:

Burmester G, Gabay C, Arikan D, Cardoso A, Kalabic J, Pfeifer N, Varothai NA, Florentinus S, Smolen JS. Thromboembolic Events Are Not Associated with Anti-Adalimumab Antibodies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/thromboembolic-events-are-not-associated-with-anti-adalimumab-antibodies/. Accessed .

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