Background/Purpose:

Much has been written about infections associated with biologic agents in patients with rheumatoid arthritis (RA). However, less is known about the risk of subsequent infections in RA patients who resume biologic therapy after a serious infection.To compare the subsequent risk of hospitalized infections associated with specific biologic agents among RA patients previously hospitalized for infection while receiving anti-TNF therapy.

Methods:

Using Medicare data from 2006-2010 for 100% of beneficiaries with RA, we identified patients who were hospitalized with infection while on anti-TNF agents and who had US Medicare fee-for-service hospital, physician and prescription drug coverage continuously in the 6 months before the hospitalization discharge date and throughout follow up. Follow-up began 60 days after hospital discharge and ended at the earliest of subsequent infection, loss of Medicare coverage or after 18 months. We determined biologic exposure on each person-day during follow-up and treated exposure as time varying. Confounding was controlled through a person-specific infection risk score that was separately derived among new users of anti-TNF and non-biologic DMARDs. We calculated the incidence rate of subsequent hospitalized infection for each biologic and used cluster adjusted Cox regression to evaluate the association between specific biologics and subsequent infection, controlling for the decile of the infection risk score, types of anti-TNF use, steroid use during baseline, non-biologic DMARD use during baseline and coexisting biologic exposures.

Results:

During follow-up of 10,794 hospitalized infections while exposed to anti-TNF therapy, we identified 7,807 person-years of exposure to target biologics and 2,666 subsequent hospitalized infections; of this exposure time 4% was on abatacept, 2% on rituximab and 94% on anti-TNFs, including 23% on etanercept, 18% on adalimumab and 53% on infliximab. Abatacept users had the lowest crude incidence rate of subsequent infection, and etanercept users had the highest. After adjusting for infection risk score decile, the original anti-TNF medication and other potential confounders, abatacept (hazard ratio (HR): 0.80, 95% CI: 0.64-0.99) and etanercept (HR: 0.83, 95% CI: 0.72-0.96) users had significantly lower risks of infection compared to infliximab users.

Conclusion:

Among RA patients who experienced a hospitalized infection while on anti-TNF therapy, the risk of subsequent hospitalized infection was lower for abatacept and etanercept than for other commonly prescribed biologic therapies. 

 

Table : Number of events, crude incidence rates (IRs) and adjusted Hazard Ratios (HR) for subsequent hospitalized infection by biologic*
Biologic Exposure	Events	PYs†	IR / 100 PYs	Crude HR (95% CI)	Adjusted HR (95% CI) ‡
Abatacept	88	333	26.5	0.88 (0.71-1.09)	0.80 (0.64-0.99)
Rituximab	38	133	28.5	0.93 (0.68-1.28)	0.85 (0.62-1.18)
Etanercept	661	1,831	36.1	1.07 (0.98-1.17)	0.83 (0.72-0.96)
Adalimumab	497	1,423	34.9	1.03 (0.93-1.14)	0.92 (0.79-1.07)
Infliximab	1382	4,087	33.8	1.0 (ref)	1.0 (ref)
*Biologic exposure was defined as the days’ supply field from filled prescriptions to which was added  a 30-day ‘extension’ period † Person years ‡Adjusted for the decile of disease risk score, types of anti-TNF use before the index hospitalization, steroid dose during baseline, methotrexate use during baseline, infection type for the index hospitalization and concurrent biologic exposures during follow up.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-subsequent-infection-among-rheumatoid-arthritis-patients-using-biologics/