Supplementary Table 1. Cohort studies of infections associated with biologic DMARD use in patients with rheumatoid arthritis.

Article Country Main Comparator Outcome Finding New-user design

Active-comparator design

Chiang 2014S1

Taiwan Etanercept Adalimumab Serious infection Adjusted HR was 2.04 for etanercept. Yes Yes

Bounthavong 2014S2

USA Etanercept Adalimumab, Infliximab

Infection event (secondary)

No significant difference in rates of infections Yes Yes

Alawneh 2014S3

Jordan Infliximab Adalimumab, Etanercept

Severe infection and tuberculosis

No significant difference among groups No Yes

Yun 2014S4

USA TNF inhibitors Abatacept, Rituximab Hospitalized infection

Adjusted HR 0.80 for abatacept and 0.83 for etanercept.

No Yes

Yoo 2014S5

Korea Infliximab Adalimumab Serious infection and tuberculosis

No significant difference in rates of infections Yes Yes

Curtis 2014S6

USA TNF inhibitors Rituximab, Abatacept Hospitalized bacterial infections

HR 2.3 for infliximab compared to etanercept Yes Yes

Cho 2014S7

Korea, Japan

Korean TNF inhibitor users

Japanese TNF inhibitor users

Serious adverse events including infection

Higher unadjusted incidence rate of infection in Japan

Yes Yes

Ke 2013S8

Taiwan TNF inhibitors Traditional DMARDs Active tuberculosis Adjusted HR was 4.87 for TNF inhibitor users. Yes Yes

Koike 2014S9

Japan Tocilizumab - Serious infection Higher age, longer RA duration, comorbidity, and glucocorticoids were risk factors.

Yes No

Lee 2013S10

Korea TNF inhibitors General population Mycobacterial infections

Standardize incidence ratio of 6.4. No No

Johnston 2013S11

USA Abatacept, Adalimumab, Etanercept, Infliximab as second agents

Rituximab as second agent

Infections Compared to rituximab, adjusted HR were elevated for adalimumab, etanercept, infliximab.

Yes Yes

Bello 2012S12

Italy Biological DMARDs General population Influenza-like illness Increased incidence of influenza-like illness No No

van Dartel 2013S13

Netherlands

Etanercept Adalimumab, Infliximab

Serious infections Adjusted HR was significantly lower for etanercept. Yes Yes

Curtis 2012S14

USA Infliximab Etanercept, Adalimumab

Serious infections Infliximab had a significantly higher adjusted rates. Yes Yes

Atzeni 2012S15

Italy Infliximab Adalimumab, Etanercept

Serious infections Adjusted HR was increased for infliximab and adalimumab compared to etanercept.

Yes Yes

Thyagarajan 2012S16

USA Adalimumab Etanercept, Infliximab Fatal infections (secondary)

Rates of fatal infections were similar among three agents.

Yes Yes

Dewedar 2012S17

Saudi Arabia

TNF inhibitors Traditional DMARDs Adverse drug effects including infections

Unadjusted rates were not significantly different. No Yes

Ventura-Ríos 2012S18

Mexico Biological DMARDs Traditional DMARDs Safety including infections

Higher infection risk than traditional bDMARDs. No Yes

Nguyen- USA TNF inhibitor switcher TNF inhibitor non- First significant Adjusted HR was 0.93 No Yes

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Khoa 2012S19

switcher infection

Galloway 2013S20

UK Biological DMARDs Traditional DMARDs Soft tissue infections Adjusted HR for zoster was high for bDMARDs. No Yes

Sakai 2012S21

Japan TNF inhibitors Traditional DMARDs Serious infections Adjusted incidence rate ratio was elevated during the first year for biological bDMARDs.

Yes Yes

Grijalva 2011S22

USA TNF inhibitors Traditional DMARDs Hospitalized infections

TNF inhibitor initiation was not associated with an increased risk of hospitalized serious infections.

Yes Yes

Lang 2012S23

Germany Tocilizumab - Infections Among tocilizumab users, risk factors included longer disease duration and exposure to multiple previous treatments.

Yes No

Koike 2011S24

Japan Tocilizumab - Safety including infections

Most frequent serious adverse events were infections.

Yes No

Strangfeld 2011S25

Germany TNF inhibitors Traditional DMARDs Serious infections Adjusted incidence rate ratio was 1.8 for TNF inhibitors.

Yes Yes

Galloway 2011S26

UK TNF inhibitors Traditional DMARDs Septic arthritis Adjusted HR was 2.3 for TNF inhibitors. No Yes

Curtis 2011S27

USA Biological DMARDs Biological DMARD switchers

Serious infections Patient risk factors contributed more to infections. Yes Yes

Komano 2011S28

Japan TNF inhibitors Traditional DMARDs Serious infections Adjusted RR was 2.37 for TNF inhibitors. No Yes

Lane 2011S29

USA TNF inhibitors Traditional DMARDs Hospitalized infections

Adjusted HR was 1.24 for TNF inhibitors. Yes Yes

Momohara 2011S30

Japan Biological DMARDs Traditional DMARDs Acute surgical-site infections

Adjusted RR was elevated for biological bDMARDs No Yes

Galloway 2011S31

UK TNF inhibitors Traditional DMARDs Serious infections Adjusted HR was 1.8 for TNF inhibitors during the first 6 months.

No Yes

Gottenberg 2010S32

France Rituximab - Severe infections Baseline comorbidities were associated with infections.

Yes No

Suwannalai 2009S33

Thailand Etanercept Infliximab Serious infections Overall infection rate was higher among infliximab users.

Yes Yes

Peña-Sagredo 2009S34

Spain TNF inhibitors Traditional DMARDs Non-typhi Salmonella infections

Infection incidence was not elevated, but was more severe.

No Yes

Dixon 2010S35

UK Infliximab, adalimumab

Etanercept Tuberculosis Tuberculosis incidence were elevated in infliximab and adalimumab compared to etanercept.

Yes Yes

Greenberg 2010S36

USA TNF inhibitors with or without methotrexate, methotrexate

Other Traditional DMARDs

Infections including opportunistic

TNF inhibitors and methotrexate users had increased risk of infection compared to other Traditional bDMARDs

No Yes

Aggarwal 2009S37

USA Etanercept - Tuberculosis No active tuberculosis was found. Yes No

Strangfeld 2009S38

Germany TNF inhibitors Traditional DMARDs Herpes zoster No increased risk for TNF inhibitor class, HR 1.82 for infliximab and adalimumab.

Yes Yes

Peña-Sagredo

Spain TNF inhibitors - Listeria infections Incidence was higher than general population. Yes No

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2008S39

Favalli 2009S40

Italy Infliximab Adalimumab, Etanercept

Serious infections Incidence did not differ among TNF inhibitors. Yes No

Garcia-Vidal 2009S41

Spain Infliximab - Opportunistic infection

Incidence was elevated during first year of treatment.

Yes No

Curtis 2007S42

USA TNF inhibitors Methotrexate Bacterial infections Incidence of infection was elevated during first 6 months of TNF inhibitor treatment.

Yes Yes

Dixon 2007S43

UK TNF inhibitors Traditional DMARDs Serious infection Incidence rate ratio 4.6 for TNF inhibitors in first 90 days.

No Yes

Curtis 2007S44

USA TNF inhibitors Methotrexate Serious bacterial infection

Adjusted HR was 1.9 for TNF inhibitors. No Yes

Seong 2007S45

Korea TNF inhibitors General population Tuberculosis Adjusted RR was 8.9 for TNF inhibitor users compared to general population.

No No

den Broeder 2007S46

Netherlands

TNF inhibitors Traditional DMARDs Surgical site infections

No elevated risk of surgical site infection was associated with TNF inhibitors.

No Yes

Salliot 2007S47

France TNF inhibitors Traditional DMARDs Serious infections Relative risk was 3.1 compared to period before TNF inhibitor initiation.

No Yes

Dixon 2006S48

UK TNF inhibitors Traditional DMARDs Serious infections Serious skin and soft tissue infection was increased in TNF inhibitors.

No Yes

Giles 2006S49

USA TNF inhibitors Traditional DMARDs Serious postoperative orthopedic infections

Significant association between TNF inhibitors and postoperative infection.

No Yes

Listing 2005S50

Germany Etanercept, Infliximab Traditional DMARDs Serious and nonserious infections

Adjusted RR was non-significant. Yes Yes

Maillard 2005S51

France Infliximab - Severe pyogenic infections

Older age and high-dose glucocorticoid therapy were associated with an increased risk.

No No

Neven 2005S52

Netherlands

Infliximab - Adverse drug effects including infections

Infection was the most common adverse event. Yes No

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