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Scientific Abstracts
life (HRQoL) and ability to perform daily activities. We report here comparative
findings from patient reported outcomes (PROs) assessed with subcutaneous
abatacept (ABA) or adalimumab (ADA) on background methotrexate (MTX)
in the first head-to-head study, AMPLE (Abatacept Versus Adalimumab
Comparison in Biologic Naive RA Subjects with Background Methotrexate).
Objectives: To compare changes in PROs at 1 year in patients with RA treated
with ABA or ADA, both on background MTX.
Methods: AMPLE is a phase IIIb, randomized, investigator-blinded study of 2
year duration. Biologic-nave patients with active RA and inadequate response
to MTX were randomized to either 125 mg ABA weekly or 40 mg ADA bi-weekly
in combination with MTX. PROs evaluated through Day 365 included: HRQoL
assessed using SF-36 (including Physical and Mental Component Summary
subscores [PCS and MCS]), activity limitation over the previous 30 days,
with the Activity Limitation Questionnaire (ALQ)1, productivity,with the work
productivity and activity impairment questionnaire for RA(WPAI:RA)2, physical
and psychosocial independence, captured using items from HAQ, SF-36, and
ALQ.3 Other PROs previously reported from AMPLE, include: patient pain,
patient global assessment, fatigue, and physical function.4 All efficacy analyses
were done using the intent-to-treat population. Baseline characteristics were
analyzed descriptively and changes in PROs from baseline were assessed
using ANCOVA.
Results: Baseline demographic and clinical characteristics of the ABA (n=318)
and ADA (n=328) treatment arms were similar4. Improvements in all domains
of the SF-36, including PCS and MCS observed at Day 169 were maintained
at Day 365. At baseline, the number of days (mean SD) with limited activity
over the previous 30 days was 11.7 10.4 and 12.4 10.3, respectively, for
ABA and ADA. At Day 169, number of days with limited activity was reduced to
5.5 8.2 and 5.9 8.1, which remained sustained at Day 365 at 5.1 7.4 and
6.1 8.3 days for ABA and ADA, respectively. Improvements in productivity
were seen in both treatment groups; however, numerically greater decreases
in work and activity impairment were seen earlier at Day 169, with ABA; at
Day 365, improvements were comparable among both treatment groups. At
baseline, psychosocial independence was 0.3 0.9 and 0.3 0.8 for ABA and
ADA respectively which improved at Day 365 to 1.01.0 and 1.0 1.0. Physical
independence improved from 0.5 1.1 and 0.5 1.0 at baseline to 1.4 0.9 and
1.41.0 at Day 365 in the two groups.
Conclusions: Both SC abatacept and adalimumab, on background MTX, led to
comparable improvements in HRQoL, work productivity, activity limitation and
physical and psychosocial independence. Improvements in these measures
were evident at Day 169 and were sustained through Day 365.
References: 1Wells G et al. J Rheumatol. 2007;34(2):280-289.
2
http://www.reillyassociates.net/WPAI_SHP.html
3
Hassett AL et al. Curr Med Res Opin. 2008;24(5):1443-1453.
4
Weinblatt et al. Arthritis Rheum. 2013; 65 (1):28-38
Disclosure of Interest: R. Fleischmann Grant/research support from:
Genentech Inc., Roche, Abbott, Amgen, UCB, Pfizer, Bristol-Myers Squibb,
Eli-Lilly, Sanofi-Aventis, Lexicon, MSD, Novartis, BiogenIdec, Astellas,
Astra-Zeneca, Jansen, Consultant for: (Roche, Abbott, Amgen, UCB, Pfizer,
Bristol-Myers Squibb, Eli-Lilly, Sanofi-Aventis, Lexicon, Novartis, Astellas,
Astra-Zeneca, Jansen, HGS, M. Weinblatt Grant/research support from:
Bristol-Myers Squibb, Abbott, Consultant for: Bristol-Myers Squibb, Abbott, M.
Schiff Consultant for: Bristol-Myers Squibb, Abbott, Speakers bureau: BristolMyers Squibb, Abbott, D. Khanna Consultant for: Bristol-Myers Squibb, L.
Rosenblatt Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers
Squibb, M. Maldonado Shareholder of: Bristol-Myers Squibb, Employee of:
Bristol-Myers Squibb, D. Furst Grant/research support from: Abbott, Actelion,
Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB,
Consultant for: Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, Gilead,
GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers bureau:
Abbott, Actelion, UCB (CME ONLY)

SAT0130

DEFINING THE OPTIMAL BIOLOGICAL MONOTHERAPY

IN RHEUMATOID ARTHRITIS (RA): NETWORK METAANALYSIS OF RANDOMIZED TRIALS

R. Christensen1, S. Tarp1, D. E. Furst2, M. stergaard3, T. Lorenzen4, M. S.

Hansen5, J. A. Singh6, E. H. Choy7, M. Boers8, M. E. Suarez-Almazor9, B.
Ejbjerg10, L. E. Kristensen11, H. Bliddal1. 1Musculoskeletal Statistics Unit, The
Parker Institute, Copenhagen University Hospital, Frederiksberg, Denmark,
2
David Geffen School of Medicine, UCLA, LA, United States, 3Dept Rheum,
Glostrup Hospital, Glostrup, 4Dept Rheum, Silkeborg Hospital, Silkeborg,
5
Dept Rheum, Copenhagen University Hospital, Gentofte, Denmark,
6
University of Alabama, Birmingham, United States, 7Cardiff School of
Medicine, Cardiff, United Kingdom, 8Dept Epi Biostat, VU University Medical
Center, Amsterdam, Netherlands, 9University of Texas, Houston, United
States, 10Slagelse Hospital, Slagelse, Denmark, 11Lund University, Lund,
Sweden
Background: Methotrexate (MTX) is considered the anchor drug in RA, both as
monotherapy, as well as for its ability to increase the efficacy of biologic agents
when used in combination [1]. Some RA patients have to discontinue DMARD
therapy. Thus, it is important to define the optimal biological monotherapy in
RA patients.
Objectives: To review the evidence for short-term efficacy and safety of
biologic monotherapy in RA. The aim was to define the optimal biological
monotherapy in RA patients without concomitant use of any DMARD therapy.
Methods: Systematic review and Network Meta-Analysis of RCTs with
DMARD inadequate responders (IR) and DMARD nave RA patients,

Saturday, 15 June 2013

625

comparing biologic agents in monotherapy with either placebo (no DMARD)

or DMARD, were considered eligible for inclusion. The co-primary outcomes
were the number of patients achieving an ACR50 response, and the number
discontinuing therapy due to adverse events (AE) [2] preferably after 6 months
(3-12 months), respectively. The network meta-analysis was based on mixedeffects logistic regression (GLMM modelled in SAS) [2]; combining statistical
inference from both direct and indirect comparisons of the treatment effects
between biologics. All dosages applied for all of the nine biologics. Results are
reported as odds ratios (OR [95%CI]). For sensitivity, in terms of the included
patients, we compared DMARD IR responder trials with DMARD Nave trials.
Results: From the literature search 27 individual studies (7,938 patients)
were included: abatacept [Aba:1], adalimumab [Ada:5], anakinra [Ana:2],
certolizumab [Cer:2], etanercept [Eta:6], golimumab [Gol:3], infliximab [Inf:1],
rituximab [Rit:1] and tocilizumab [Toc:6]. The network only included one closed
loop with biologics head-to-head: ADACTA (Toc vs. Ada) [3]. Benefit (ACR50):
Ana was statistically less likely than Ada, Eta, Gol, and Toc, respectively, to
have a clinical response (p<0.05). The odds for responding was statistically
higher (p<0.05) for Toc compared to Aba (3.9[1.2;12.4]), Ada (2.1[1.2;3.6]), and
Inf (7.7[1.8;32.4]), respectively. Finally, Eta was statistically more likely to result
in a response than Inf (5.6[1.3;23.9]). Harm (Withdrawal d/t AEs): Gol seemed
less likely to cause withdrawal from side effects (p<0.05) compared to Ada
(0.4[0.1;0.9]), Ana (0.3[0.1;0.8]), Cer (0.3[0.1;1.0]), Inf (0.2[0.1;1.0]), and Toc
(0.4[0.1;0.8]). For sensitivity, the ACR50 estimates were compared with the
direct comparison of Ada vs. Toc [3]; the model apparently did not build on
incoherence, as data from the ADACTA study reported a comparable effect
size (OR=2.3 [1.5; 3.7]).
Conclusions: All biologics are not equal. In RA patients who need biologic
therapy without concomitant use of DMARDs, some biologics are better than
others with respect to ACR50 responses.
References: [1] Smolen J, et al. Ann Rheum Dis. 2010;69(6):964-75.
[2] Singh JA, et al. CMAJ. 2009;181(11):787-96.
[3] Gabay C, et al. Lancet (Accepted, 2013)
Acknowledgedments: Musculoskeletal Statistics Unit, The Parker Institute
receives support via research grants from the Oak Foundation.
Disclosure of Interest: R. Christensen Grant/research support from: This
particular study, including both the protocol and subsequent manuscript,
has been supported by a grant from Roche; the grant was provided as an
unrestricted grant to Musculoskeletal Statistics Unit, The Parker Institute.,
Speakers bureau: Abbott, BMS, Pfizer, Roche, MSD, Expanscience, Biogen
Idec, Ipsen, Novartis, Bayer, S. Tarp: None Declared, D. Furst: None Declared,
M. stergaard: None Declared, T. Lorenzen: None Declared, M. Hansen: None
Declared, J. Singh: None Declared, E. Choy: None Declared, M. Boers: None
Declared, M. Suarez-Almazor: None Declared, B. Ejbjerg: None Declared, L.
Kristensen: None Declared, H. Bliddal: None Declared

SAT0131

LONG-TERM SAFETY OF RITUXIMAB: POOLED

ANALYSIS OF THE RHEUMATOID ARTHRITIS GLOBAL
CLINICAL TRIAL PROGRAMME OVER 11 YEARS

R. F. van Vollenhoven1, P. Emery2, C. O. Bingham3, E. Keystone4, R. M.

Fleischmann5, D. Furst6, E. W. Hessey7, A. Vashishtha8, A. Mehbob7, P.
B. Lehane7. 1Department of Medicine, Karolinska Institute, Stockholm,
Sweden, 2Division of Rheumatic & Musculoskeletal Disease, University
of Leeds and Leeds Teaching Hospitals Trust, Leeds, United Kingdom,
3
Department of Medicine, The Johns Hopkins University, Baltimore, United
States, 4The Rebecca MacDonald Centre for Arthritis and Autoimmunity,
Mount Sinai Hospital, Toronto, Canada, 5Southwestern Medical Center at
Dallas, University of Texas, Dallas, 6Department of Rheumatology, UCLA,
Los Angeles, United States, 7Roche Products Limited, Welwyn Garden City,
United Kingdom, 8Genentech Inc., South San Francisco, United States
Objectives: To conduct an updated overall safety analysis of rituximab (RTX)
in RA patients in the global clinical trial programme.
Methods: Pooled observed case analysis of safety data from patients with
moderate to severe active RA treated with RTX+MTX. Patients were retreated
based on physicians determination of clinical need and evidence of active
disease (defined as either SJC and TJC 8 or DAS28 2.6). Pooled data from
patients who received placebo during placebo-controlled study periods were
also analysed.
Results: As of Sep 2012, 3595 patients (All-Exposure population) had
received up to 20 courses of RTX over the 11-yr observation period (14 816
pt-yrs). Of these patients, 1246 had >5yrs follow-up. The placebo population
comprised 818 patients (1107 pt-yrs) with a mean follow-up of 11.5 yrs. In the
All-Exposure population, infusion-related reaction (IRR) was the most frequent
adverse event (AE); most were grade 1 or 2, were rarely serious (0.5%),
and primarily occurred following the 1st infusion of the 1st course (799/3595
patients; 22%). Rates per 100 pt-yrs for AEs, serious AEs (SAEs), and
infections were not increased when compared to placebo (Table). Overall the
serious infection rate in RTX-treated patients was comparable to that observed
in placebo patients. Pneumonia was the most frequently reported serious
infection (2% of RTX patients). There were no cases of hepatitis B reactivation.
Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX patients
vs 0.09/100 pt-yrs in placebo). One confirmed case of PML in the RA clinical
trial programme has been reported, as previously described.1 Following RTX
treatment low immunoglobulin (Ig) concentrations (particularly IgM, less often
IgG) were observed. For both Ig classes, serious infection rates were similar
before and during/after development of low Ig. No increased risk of malignancy

Downloaded from http://ard.bmj.com/ on February 16, 2015 - Published by group.bmj.com

SAT0130 Defining the Optimal Biological

Monotherapy in Rheumatoid Arthritis (RA):
Network Meta-Analysis of Randomized Trials
R. Christensen, S. Tarp, D. E. Furst, M. stergaard, T. Lorenzen, M. S.
Hansen, J. A. Singh, E. H. Choy, M. Boers, M. E. Suarez-Almazor, B.
Ejbjerg, L. E. Kristensen and H. Bliddal
Ann Rheum Dis 2013 72: A625

doi: 10.1136/annrheumdis-2013-eular.1856
Updated information and services can be found at:
http://ard.bmj.com/content/72/Suppl_3/A625.1

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