The Safety of Disease Modifying Anti Rheumatic Drugs and Biologic Therapy (DBT) in Rheumatoid Arthritis

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The Safety of Disease Modifying Anti Rheumatic Drugs and Biologic Therapy

(DBT) in Rheumatoid Arthritis

Category:  17 RA‹treatment

Frederick Wolfe1, Kaleb Michaud1, Keenan2, Callegari2

1National Data Bank for Rheumatic Diseases, Wichita, KS;2Centocor, Inc.,

Malvern, NJ

Presentation Number: 372

Poster Board Number: 372

Keywords: Infliximab, Etanercept, Methotrexate

Background. Controlled clinical trials have demonstrated efficacy and safety

for major DMARD and biologic therapy (DBT). Uncontrolled observations and

use in the community has suggested increase risk for infection, and possibly

other serious adverse events (AE). However, reports from the community are

unable to provide rates of AEs, DBT comparisons, denominators of use, and

are unable to control for confounding factors. We used a large, longitudinal

data bank to assess safety related factors from 1998 through 2001.

Methods. 16,003 RA patients, enrolled continuously from the practice of 887

US rheumatologists, completed 56,719 questionnaires in up to 8 6-month

periods. Data were adjusted for disease severity by the Rheumatoid Arthritis

Disease Activity Index (RADAI), HAQ and prednisone use, and for key

socio-demographic factors (SDF) known to be linked to outcome, including

age, sex, disease duration, education, income, type of medical insurance,

and period of study entry. Analyses utilized generalized estimating

equations to compare drugs for site specific infection, site specific

hospitalization for infection, congestive heart failure, development of

autoimmune disease, and for malignancy and lymphoma within each 6 month

period of observation. All analyses were multivariate and were adjusted for

all confounders. The 5 DBT drug groups were infliximab with or without

(w/wo) MTX (INF}, etanercept w/wo MTX (ETA), leflunomide w/wo MTX (LEF), MTX

w/o INF, ETA, or LEF (MTX), and those not on INF, ET, LEF, or MTX (NOT). For

simplicity, hospitalization rates relating to 859 hospitalizations are

presented, but few differences were noted when all variables were examined.

Results. Regardless of outcome selected, and compared to no prednisone,

prednisone use was significantly associated with increased risk of

hospitalization for infection: Blood odds ratio 1.88 (95% CI 1.21, 2.94),

lung OR 1.99 (1.60, 2.47), renal OR 1.62 (1.06, 2.18), skeletal OR 1.55

(1.21, 2.98), and skin OR 1.90 (1.06, 2.25). Compared with the 29% of

patients on NOT, none of the other DBT drug categories were associated with

increased risk of infection. In addition, rates of infection did not differ

between INF and ETA. MTX had a significantly lower rate of blood infection

compared with INF and ETA, and of skeletal infection compared with LEF. Risk

of congestive heart failure and development of autoimmune disease was not

increased in the DBT categories compared with NOT; nor were there group

differences within the DBT groups.

Conclusions. Prednisone is independently associated with increased risk for

infections. There is no difference in rates of hospitalization for infection

between those on DBT and those not on such therapies. The 2 TNF agents had

similar patterns of infection. In this large, longitudinal study of RA,

there is no evidence of significantly increased infection rates, congestive

heart failure, or induction of autoimmune disease.