A recent article (Clin Infect Dis 2013; 57: 1318-30 -thanks to Jeff Lewis for this reference) summarized the pediatric literature on infectious complications associated with tumor necrosis factor-α (TNF) inhibitors for both Juvenile Idiopathic Arthritis (JIA) and Inflammatory Bowel Disease (IBD).
In total 33 studies for JIA were included and 39 studies for IBD. Many others were excluded due to overlapping cohorts or lack of sufficient data.
For JIA, the authors identified 296 infliximab (IFX) patients, 2465 etanercept patients, and 242 adalimumab patients. Most infectious were mild and mainly viral etiology. For example, 1016 upper respiratory illnesses with etanercept were reported. However there were a significant number of more serious infections which included lower respiratory infections (n=37), cellulitis/abscess (n=15), histoplasmosis (n=2), and meningitis (n=4). Four patients had infectious fatalities.
Similarly, for IBD, most patients had mild infections. Among 1407 IFX patients and 241 adalimumab (ADA) patients, there were 105 URIs noted. Again, more serious infectious were noted in many. Four fatalities were reported; 1 was due to disseminated CMV, 1 due to bacterial sepsis, and 2 were due to central line infections.
When examining this report, the question of reporting bias cannot be avoided. The various reports that were summarized included 30 prospective studies, 23 retrospective studies, and 19 various reports (case reports, case series, and FDA reports). The composite, in my view, likely overestimates the risk of serious infections. In addition, many of the infections may have been due to concurrent immunosuppressive therapy, but the details for this are lacking.
With regard to microbiology:
- 5 JIA patients had tuberculosis; there were no tuberculosis cases reported in the IBD cohort
- Varicella/zoster was the most frequent viral infection and was frequently severe. In JIA cohort, there were 39 VZV cases (11 severe); among IBD cohort, there were 16 VZV cases (3 severe).
Bottomline: Given the frequent use of anti-TNF agents, better prospective pediatric data are needed. In addition, careful analysis of the data is needed for better attribution; the risk for many of these infections is likely due to concurrent medications like corticosteroids.
Clin Gastroenterol Hepatol 2013; 11: 826-31. In a prospective cohort of 200 anti-TNF-naive adult patients (100 treated with IFX and 100 with ADA), the effectiveness was similar for IFX and ADA at both 1 and 2 year followup. Improved efficacy was noted when these agents were combined with immunomodulators, though this was statistically significant for IFX. The total patient response was 63.5% at 1 year and 45% at 2 years.