ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2337

Serious Adverse Events Associated With Using Biological Agents To Treat Rheumatic Diseases: Network Meta-Analysis From a National Guideline Panel

Simon Tarp1, Ulrik Tarp2, Lis S. Andersen3, Tove Lorenzen4, Hanne M. Lindegaard5, Michael Stoltenberg6, Hanne S. Jensen7, Birgitte Brock8, Camilla M. Mikkelsen9, Dorte V. Jensen10, Karsten Asmussen7, Troels Herlin11 and Robin Christensen1, 1Musculoskeletal Statistics Unit, The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark, 2Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark, 3Department of Rheumatology, Copenhagen University Hospital, Gentofte, Denmark, 4Department of Rheumatology, Region Hospital Silkeborg, Silkeborg, Denmark, 5Department of Rheumatology, Odense University Hospital, Odense, Denmark, 6Department of Rheumatology, Copenhagen University Hospital, Køge, Denmark, 7Department of Rheumatology, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark, 8Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark, 9The Capital Region of Denmark Hospital Pharmacy, Medicine Information Centre, Copenhagen NV, Denmark, 10The Danish Rheumatologic Database (DANBIO), Center of Rheumatology and Spine Diseases VRR, Copenhagen University Hospital, Glostrup, Denmark, 11Pediatric Rheumatology Clinic, Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy III

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Clinical guidelines are needed to help clinicians provide optimal medical treatment and advise patients about the potential hazards associated with certain drugs.

Our objective was to compare the number of serious adverse events (SAEs) for the biologics available for inflammatory arthritis (i.e., rheumatoid arthritis, psoriatic arthritis, and spondylarthritis), enabling a national consensus on safety associated with using these drugs.

Methods:

A national guideline panel consisting of clinical experts and methodologists conducted systematic literature searches, identifying randomized controlled trials (RCTs) and inviting all pharmaceutical companies marketing the biologics in question. Eligible RCTs included patients with rheumatoid arthritis, psoriatic arthritis, or spondylarthritis, where approved biologics in standard dose were compared with another biologic or placebo. One reviewer extracted data on the number of patients with an SAE from included trials, and a second reviewer confirmed data, which also entailed inviting the respective pharmaceutical companies to verify extracted data regarding their own drug(s). The network meta-analysis was based on mixed-effects logistic regression (modeled in SAS) [1] combining statistical inference from both direct and indirect comparisons of the treatment effects of among the biologics. Results were reported as odds ratios (OR [95%CI]). For sensitivity, we explored trial duration using weeks as a covariate in the model.

Results:

From the 94 identified RCTs complying with our eligibility criteria, 7 did not report data on SAEs. Thus, the meta-analysis included 87 trials (27,333 patients) comprising 85 placebo and 90 biologic trial arms: abatacept (8), adalimumab (22), anakinra (2), certolizumab (8), etanercept (15), golimumab (8), infliximab (14), rituximab (5), and tocilizumab (8). The odds for SAEs were statistically higher (P < 0.05) for certolizumab and tocilizumab compared with the placebo (1.60 [1.19;2.16]; P = 0.0022 and 1.33 [1.03;1.70]; P = 0.028 respectively). Certolizumab was statistically more likely to result in SAEs compared with all of the following: golimumab (2.02[1.26;3.25]; P = 0.0042), etanercept (1.70[1.15;2.51]; P = 0.0084), rituximab (1.68[1.06;2.66]; P = 0.027), abatacept (1.53 [1.05;2.25]; P = 0.028), and adalimumab (1.44[1.02;2.02]; P = 0.037). Further, tocilizumab was statistically more likely to result in SAEs than golimumab (1.67[1.07;2.62]; P = 0.025). All other comparisons showed no statistically significant differences (P > 0.05).

Conclusion :

This network meta-analysis of RCTs provides empirical evidence that certolizumab and tocilizumab both present an increased likelihood of SAEs compared with placebo. Supported by a recent Cochrane review [2] the Danish guideline panel concluded that certolizumab was more likely to cause SAEs compared with several other biologics and thus made a weak recommendation against its use.

 

References:

[1] Singh JA, et al. CMAJ. 2009;181(11):787-96.

[2] Singh JA, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;2:CD008794

Disclosure:

S. Tarp,
None;

U. Tarp,
None;

L. S. Andersen,
None;

T. Lorenzen,

Roche and Pfizer,

6;

H. M. Lindegaard,

Lilly, MSD, Nordpharma, Roche Pharmaceuticals,

2,

Roche Pharmaceuticals, MSD,

5;

M. Stoltenberg,

Abbvie, BMS, MSD, Pfizer, Roche, and UCB,

8,

BMS and UCB,

6,

Roche Pharmaceuticals,

5;

H. S. Jensen,
None;

B. Brock,

AstraZeneca, GSK, and Novartis,

8;

C. M. Mikkelsen,
None;

D. V. Jensen,

AbbVie,

2;

K. Asmussen,

MSD, abbvie, Pfizer, BMS and UCB,

5,

MSD, abbvie, Pfizer, BMS and UCB,

8;

T. Herlin,
None;

R. Christensen,

Abbott, Axellus A/S, Bristol-Myers Squibb, Cambridge Weight Plan, Norpharma, Pfizer, and Roche,

5,

Axellus A/S, Cambridge Weight Plan, Mundipharma, and Roche,

2,

Abbott, Axellus, Bayer HealthCare Pharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Cambridge Weight Plan, Ipsen, Laboratoires Expanscience, MSD, Mundipharma, Norpharma, Pfizer, Roche, and Wyeth,

8.

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