ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2641

Safety of Synthetic and Biological Dmards: Slr Informing the Update of the EULAR Recommendations for the Management of RA

Sofia Ramiro1, Alexandre Sepriano1, Katerina Chatzidionysiou2, Jackie L. Nam3, Josef Smolen4, Désirée van der Heijde5, Maxime Dougados6, Ronald van Vollenhoven7, Johannes WJ Bijlsma8, GR Burmester9, Marieke Scholte-Voshaar10 and RBM Landewé11, 1Leiden University Medical Center, Leiden, Netherlands, 2Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), The Karolinska Institute, Stockholm, Sweden, 3Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom, 4Internal Medicine III, Div. of Rheumatology, Medical University of Vienna, Vienna, Austria, 5Rheumatology, Leiden University Medical Center, Leiden, Netherlands, 6Paris Descartes University, Paris, France, 7Amsterdam Rheumatology Center, Amsterdam, Netherlands, 8Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, Netherlands, 9Charité – University Medicine Berlin, Berlin, Germany, 10EULAR Standing Committee of People with Arthritis/Rheumatism in Europe, Zurich, Switzerland, 11Amsterdam Medical Center, Amsterdam, Netherlands

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: ,

Session Information

Date: Tuesday, November 15, 2016

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

Session Type: ACR Poster Session C

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

Background/Purpose: As part of the update of the EULAR recommendations for the management of RA, we performed a systematic literature review to assess the safety of synthetic (s) and biological (b) DMARDs for the management of RA.

Methods:  Observational studies comparing any DMARD with another intervention for the management of patients with RA were identified by searches in Medline, Embase and Cochrane datasets (2013-2016). Interventions were any bDMARD, sDMARD or glucocorticoid and a comparator group was required for the study to be included. All safety outcomes were included. Observational studies, including registries, have been chosen, as they better reflect routine care and have a longer follow-up. Risk of bias (RoB) was assessed according to the Hayden’s tool.

Results: Of 4,436 articles screened, a total of 25 papers met the inclusion criteria: 15 dealt with serious infections, 4 focused on cancer, 4 on cardiovascular events and 2 on interstitial lung disease. Studies were heterogeneous precluding meta-analysis. Five studies on serious infections were found and they showed no increased risk of serious infections in bDMARDs (both TNFi and non-TNFi) compared to conventional (c)sDMARDs (Table). The 2 low RoB studies showed no increased risk, while 2 of the 3 high RoB studies showed an increased risk of serious infections (Table). Eight studies, 1 at low RoB, 4 moderate RoB and 3 high RoB, showed no difference in the risk of serious infections between different bDMARDs (Table). One study at low RoB found no increased risk of herpes zoster in TNFi or non-TNFi. Based on 3 studies, all at low RoB, (overall) cancer does not occur more frequently in bDMARDs vs csDMARDs. The same holds true for solid cancers (2 low RoB studies). Based on one low RoB study, non-melanoma skin cancer does not occur more frequently in TNFi or rituximab vs csDMARDs; it may occur more frequently with abatacept (aHR 15.3 [95%CI 2.1; 114.0], but this is based on 2 cases only. One low RoB study addressing infections also analysed mortality, finding that mortality may be lower in bDMARDs, namely etanercept (aHR 0.7 [0.5; 0.9]), vs csDMARDs.

Conclusion: No increased risk of infections was found in patients under bDMARDs (TNFi or non-TNFi) vs csDMARDs, which contrasts to previous findings and possibly reflects an adaptation of clinical practice to avoid the risk of infections. No increased risk of malignancies was found, which is in line with previous findings. Table: Risk of serious infectious in patients on bDMARDs (observational studies)

Study ID

Registry

Intervention

Control

aHR (i vs c)

Risk of Bias

bDMARD vs csDMARD

Aaltonen 2015

National Register for Biologic Treatment in Finland (ROB-FIN)

TNFi

csDMARDs

0.9 (0.6; 1.4)

Low

ADA

1.0 (0.6; 1.6)

ETA

0.8 (0.5; 1.3)

IFX

1.2 (0.6; 2.3)

RTX

1.1 (0.6; 1.9)

Chiu 2014

Taiwan’s National Health Insurance Research Database

TNFi

csDMARDs

1.0 (0.9; 1.2)*

High

Lampropoulos 2015

Files Laiko University Hospital

bDMARDs

csDMARDs

6.9 (3.1; 15.4)

High

Miranda 2014

Files Colombian hospital

bDMARDs

csDMARDs

2.7 (1.1; 6.3)

High

Morgan 2014

BSRBR

ETA

csDMARDs

1.0 (0.8; 1.3)

Low

bDMARD vs bDMARD

Aaltonen 2015

National Register for Biologic Treatment in Finland (ROB-FIN)

RTX

TNFi

1.4 (0.8; 2.6)

Low

Chiang 2014

Taiwan’s National Health Insurance Research Database

ETA

ADA

2.0 (1.1; 3.6)*

High

Chiu 2014

ADA

ETA

1.8 (1.2; 2.8)

High

Curtis 2014

US Veterans

(claims dataset)

ABA

ETA

1.1 (0.6; 2.1)

Moderate

ADA

1.4 (0.9; 2.2)

IFX

2.3 (1.3; 4.0)

RTX

1.4 (0.8; 2.6)

Johnston 2013

MarketScan

(claims dataset)

ABA

RTX

1.2 (0.8; §)

Moderate

ADA

1.1 (0.7; 1.7)

ETA

1.3 (0.8; 2.0)

IFX

1.6 (1.0; 2.6)

Lampropoulos 2015

Files Laiko University Hospital

ADA

IFX

1.1 (p=0.819)

High

ETA

0.7 (p=0.559)

Sakai 2015

REAL

TCZ

TNFi

2.2 (0.9; 5.4)

Moderate

Yun 2016

Medicare claims dataset

ADA

ABA

1.1 (0.9; 1.3)

Moderate

CZP

1.1 (0.9; 1.3)

ETA

1.2 (1.1; 1.5)

IFX

1.4 (1.2; 1.6)

GOL

1.1 (0.9; 1.4)

RTX

1.4 (1.2; 1.5)

TCZ

1.1 (0.9; 1.3)

Disclosure: S. Ramiro, None; A. Sepriano, None; K. Chatzidionysiou, None; J. L. Nam, None; J. Smolen, Amgen, Abbvie, Astra-Zeneca, Astro, BMS, Celgene, Glaxo, ILTOO, Janssen, Merck-Serono, MSD, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, UCB, 5; D. van der Heijde, AbbVie, Amgen, Astellas, AstraZeneca, BMS, Celgene, Daiichi, Eli-Lilly, Galapagos, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, 5,Director of Imaging Rheumatology bv, 3; M. Dougados, AbbVie, Pfizer, Novartis, MSD, 5,AbbVie, Pfizer, Novartis, MSD, 2; R. van Vollenhoven, AbbVie, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, UCB Pharma, 2,AbbVie, Biotest, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Eli-Lilly, Merck, Pfizer, Roche, UCB Pharma, Vertex, 5; J. W. Bijlsma, Roche, AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, and UCB, 2; G. Burmester, UCB, 2,AbbVie, BMS, Hexal, Janssen, Lilly, MSD, Medimmune, Novartis, Pfizer, Sanofi, Roche, 5,AbbVie, BMS, Hexal, MSD, Novartis, Pfizer, Roche, 8; M. Scholte-Voshaar, None; R. Landewé, Abbott, Amgen, Centocor, Novartis, Pfizer, Rhoche, Schering-Plough, UCB, Wyeth., 2,Abbott/AbbVie, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Celgene, Janssen (formerly Centocor), Galapagos, Glaxo-Smith-Kline, Novartis, Novo-Nordisk, Merck, Pfizer, Rhoche, Schering-Plough, TiGenix, UCB, Wyeth., 5,Abbott/AbbVie, Amgen, Bristol Myers Squibb, Janssen (formerly Centocor), Merck, Pfizer, Rhoche, Schering-Plough, UCB, Wyeth., 9,Robert Landewé is director of Rheumatology Consultancy BV, which is a registered company under Dutch law., 4.

To cite this abstract in AMA style:

Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen J, van der Heijde D, Dougados M, van Vollenhoven R, Bijlsma JW, Burmester G, Scholte-Voshaar M, Landewé R. Safety of Synthetic and Biological Dmards: Slr Informing the Update of the EULAR Recommendations for the Management of RA [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/safety-of-synthetic-and-biological-dmards-slr-informing-the-update-of-the-eular-recommendations-for-the-management-of-ra/. Accessed .

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