Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: Anti-TNF therapy is a risk factor for clinical tuberculosis (TB), which has led to pre-treatment screening and increased vigilance. The extent to which these measures have reduced or removed the TB risk – with or without biological treatment – and how such risks differ between individual biologics remains less clear. We therefore sought to estimate the risk of TB in patients with rheumatoid arthritis (RA) 2002-2011 with and without exposure to biological therapy and to directly compare the risks between biological therapies.
Methods: Data from the Swedish National Population Registers, TB Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002-2011). We estimated the rate of TB in the general population (N=173,333), in a cohort of patients diagnosed with RA unexposed to biological therapy (N=37,770) and in a cohort of patients with RA exposed to biologicals (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab, N=10,803). Cox models adjusting for age, sex, country of birth, education, history of diabetes, chronic obstructive pulmonary disease and cancer were used to estimate hazard ratios and 95% confidence intervals (HR; 95%CI). We estimated the risk of TB in the biological-exposed RA population compared to the unexposed, with particular attention to risks by calendar and follow-up time, and risks associated with individual biologics.
Results: Compared to the general population, RA patients not exposed to biologicals had a 4-fold increased risk of TB (HR 4.4 (95%CI 2.7, 7.1) 30 RA, 37 general population TB cases). We identified 19 TB cases with RA who were exposed to a biological before TB diagnosis (etanercept, infliximab, adalimumab or rituximab). The rate of TB in the biological-exposed RA population has decreased since 2002. Individuals with RA who were exposed to any biological had a multivariable-adjusted HR of 4.7 (95%CI 2.5, 9.0) compared to biological-naïve patients. The HR comparing etanercept-exposed patients to biological-naïve was 1.8 (95%CI 0.5, 6.4). The HRs for adalimumab and infliximab compared to etanercept were 3.8 (95%CI 1.0, 14.8) and 2.6 (95%CI 0.6, 11.0) respectively. One case was exposed to rituximab (HR 0.9 95%CI 0.1, 10.6).
Conclusion: The risk of TB in patients with RA is increased compared to the general population. In the past decade, the risk of TB has decreased possibly due to the introduction of pre-treatment screening but remains higher than in RA patients unexposed to biologicals. Between drug comparisons showed that the lowest risk is among those exposed etanercept, but etanercept still carries an increased risk compared to biological-unexposed. The majority of cases observed over the 10 years of follow-up occurred in biological-naïve RA patients.
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Table. Incidence rates and hazard ratios of tuberculosis comparing biological-naïve to biological-exposed patients with RA, overall and stratified by calendar year of follow-up and total follow-up time. |
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Biological-Naive RA |
Biological-Exposed RA |
Hazard Ratio* (95% CI) |
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Overall |
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TB Cases/Person-years (py) |
30/219,571 |
19/48,337 |
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Overall IR, per 100,000 py (95% CI) |
13.7 (9.6, 19.6) |
39.3 (25.1, 61.6) |
4.7 (2.5, 9.0) |
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IR (95% CI) by Calendar Year |
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2002-2006 |
16.8 (10.3, 27.5) |
60.5 (32.6, 112.5) |
9.5 (3.9, 22.9) |
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2007-2011 |
12.6 (7.5, 21.4) |
21.0 (10.9, 40.3) |
2.5 (1.0, 6.2) |
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IR (95% CI) by Follow-up Time |
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<5 y |
14.4 (9.3, 22.3) |
48.3 (30.0, 77.7) |
7.0 (3.4, 14.5) |
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≥5 y |
15.0 (8.1, 27.9) |
8.2 (2.0, 32.8) |
1.4 (0.3, 7.1) |
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Drug-Specific Analysis |
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Etanercept † IR (95% CI) |
15.8 (5.1, 48.9) |
1.0 (ref) |
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Infliximab † IR (95% CI) |
67.2 (33.6, 134.4) |
2.6 (0.6, 11.0) |
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Adalimumab † IR (95% CI) |
61.1 (29.2, 128.3) |
3.8 (1.0, 14.8) |
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Rituximab † IR (95% CI) |
29.0 (4.1, 206.0) |
0.9 (0.1, 10.6) |
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*Comparing biological-exposed to biological-naïve, Adjusted for age, sex, country of birth, education, cancer, diabetes, copd. In drug-specific analysis, comparing each drug to etanercept exposure. † Exposure from date of initiation until start of next biologic. RA Rheumatoid Arthritis; TB Tuberculosis; IR Incidence Rate; CI Confidence Interval; PY Person Years; HR Hazard Ratio; |
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Disclosure:
E. V. Arkema,
None;
J. Jonsson,
None;
E. Baecklund,
None;
M. Rutting,
None;
J. Bruchfeld,
None;
N. Feltelius,
None;
J. Askling,
Pfizer Inc,
2.
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