ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 550

Long-Term Safety of Tocilizumab from Large Clinical Trial and Postmarketing Populations

Shalini Mohan1, Margaret Michalska2, Jeffrey Yourish2, Jinglan Pei2, Sara Gale1, Christine Birchwood2 and Erhan Berber2, 1Genentech, South San Francisco, CA, 2Genentech, Inc., South San Francisco, CA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , , ,

Session Information

Date: Sunday, November 5, 2017

Session Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster I: Comorbidities and Adverse Events; Efficacy and Safety of Small Molecules

Session Type: ACR Poster Session A

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

Background/Purpose: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody targeted against the interleukin-6 receptor that was approved to treat rheumatoid arthritis (RA) in the EU in 2009 and in the US in 2010, and has now completed long-term extension (LTE) follow-ups in a number of intravenous and subcutaneous RA trials. The objective of this study was to provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using data from multiple completed clinical trials and their LTEs, as well as an update from the global TCZ postmarketing safety database.

Methods: To provide an updated report on the incidence of safety events during TCZ treatment in patients with RA using data from multiple completed clinical trials and their LTEs, as well as an update from the global TCZ postmarketing safety database.

Results: The clinical trial all-exposure population consisted of 7647 TCZ-treated patients with RA (81.6% female; mean [SD] age, 52 [12.6] years), constituting 22,394 PY (mean follow-up: 2.93 years) of exposure. The overall rate (95% CI) of serious adverse events (SAE) in the clinical trial population was 14.16 (13.67-14.66) per 100 PY. Overall incidence rates for individual events for the clinical trial population are reported in the Table and were consistent in each 6-month period over the 5-year duration. The global postmarketing population included 606,937 patients. The overall spontaneous reporting rate (range) of adverse events of special interest in the postmarketing population was 9.37 (7.35-10.56) cases per 100 patients. Reporting rates of individual safety events of interest in the global postmarketing population are shown in the Table and were consistent in each 6-month period over the 7-year duration.

Conclusion: The safety profile of TCZ in the current analysis, which includes information about safety events from 12 clinical trials and their LTEs and across 7 years of real-world postmarketing reports encompassing ~ 600,000 patients, was consistent with previous safety reports. These findings are consistent with the previously reported profile of TCZ and indicate that there is no evidence of increased safety risk with increasing exposure to TCZ.

 

Table. Adverse Events Across 12 RA Clinical Trials and the Global Postmarketing Safety Database in Patients Who Received TCZ

 

RA Clinical Trial All-Exposure Population

(N = 7,647; 22,394 PY)

Global Postmarketing Safety Database Population*

(N = 606,937 Pts)

Adverse event of special interest

Patients With

≥ 1 AE (%)

Incidence Rate
(95% CI), Events/100 PY

No. of Cases

Reporting Rate (Range),

Cases/100 Pts

Serious infections

730 (9.5)

4.29

(4.02-4.57)

17,350

2.86

(2.11-3.62)

Malignancies†

242 (3.2)

1.18

(1.05-1.33)

1560

0.26

(0.18-0.51)

Injection site reactions

444 (5.8)

6.51

(6.18-6.85)

N/A

N/A

Strokes / cerebrovascular disorders

130 (1.7)

0.67

(0.56-0.78)

2069

0.34

(0.22-0.94)

Serious bleeding events

89 (1.2)

0.43

(0.35-0.52)

2440‡

0.40‡

(0.28-0.76)

Myocardial infarction

72 (0.9)

0.33

(0.26-0.42)

1946

0.32

(0.21-0.88)

Gastrointestinal perforations

39† (0.5)

0.20†

(0.15-0.27)

632

0.10

(0.06-0.30)

Serious hypersensitivity reactions§

56 (0.7)

0.26

(0.20-0.33)

N/A

N/A

Anaphylaxisǁ

21 (0.3)

0.09

(0.06-0.14)

1222

0.20

(0.09-0.38)

Serious hepatic events

9 (0.1)

0.04

(0.02-0.08)

3567‡

0. 59‡

(0.34-1.21)

Demyelination

8 (0.1)

0.04

(0.02-0.07)

66

0.01

(0.00-0.02)

AE, adverse event; N/A, not available; PY, patient year; RA, rheumatoid arthritis; TCZ, tocilizumab.

* Data are for multiple indications and from several sources (spontaneous reports, non-interventional programs, literature cases) reported following market authorization.

† Events of gastrointestinal perforations (Clinical Trial data set) and malignancies were medically confirmed.

‡ Includes both serious and non-serious cases.

§ Serious hypersensitivity was defined as a serious adverse event occurring during or within 24 hours of the injection or infusion, excluding injection site reactions, and not judged ‘unrelated’ to study treatment by the investigator.

ǁ Events of anaphylactic reactions meeting Sampson criteria (MedDRA SMQ (algorithmic) Anaphylactic reaction)).

 

Disclosure: S. Mohan, Genentech, Inc., 3; M. Michalska, Genetech, Inc., 3; J. Yourish, Genentech, Inc, 3; J. Pei, Genentech, Inc., 3; S. Gale, Genentech, Inc., 3; C. Birchwood, Genentech, Inc., 3; E. Berber, Genentech, Inc., 3.

To cite this abstract in AMA style:

Mohan S, Michalska M, Yourish J, Pei J, Gale S, Birchwood C, Berber E. Long-Term Safety of Tocilizumab from Large Clinical Trial and Postmarketing Populations [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/long-term-safety-of-tocilizumab-from-large-clinical-trial-and-postmarketing-populations/. Accessed May 26, 2022.

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