Risk of serious opportunistic infections after solid organ transplantation: interleukin-2 receptor antagonists versus polyclonal antibodies. A meta-analysis

Abstract

Background: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. Methods: PRISMA guidelines were followed and random-effects models were performed. Results: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34–2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68–0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00–2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60–3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56–0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34–0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39–0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34–0.98; p = 0.043). Results remained consistent across allografts. Conclusion: The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.

Keywords::

• IL-2 receptor antagonists
• induction
• infection
• polyclonal antibodies

Acknowledgement

The authors thank Ms. Ashley Calhoon and Ms. Elaine Litton for the excellent preparation of this manuscript.

Financial & competing interests disclosure

W Grant has received research grants from Genzyme and B Stevens has received research grants from Genzyme and consulting honoraria from Sanofi-Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Antibody induction therapy has transformed the field of transplantation in the past two decades.

• The frequency of induction antibody use varies not only between different centers around the world but also among different surgical departments within a given center.

• The preference of antibody for induction has shifted from muromomab-CD3 and horse antithymocyte globulins to rabbit antithymocyte globulins and IL-2 receptor antagonists (IL-2RAs).

• Previously published studies have not had the statistical power to evaluate the effects of polyclonal antibodies and IL-2RAs on the risk of serious infections after transplantation.

• We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2RAs in randomized clinical trials through the meta-analytic methodology.

• Polyclonal antibodies showed significantly twofold higher risk of serious opportunistic infections, while IL-2RAs were associated with significant 20% lower risk of serious opportunistic infections.

• Polyclonal antibodies were also associated with significantly higher risk of viral infections, whereas IL-2RAs were associated with significantly lower risk of cytomegalovirus (CMV) disease.

• The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies.