Table 2. Serious infections, data from meta-analyses and Pooled RCT data.
| No. of patients (TNF/ Comparator) |
Baseline disease characteristics |
Definition of infections |
At Risk Period | Duration of follow up |
Biologic Arm | Comparator Arm |
Reported incidence |
Difference b/n anti-TNF agents |
|
|---|---|---|---|---|---|---|---|---|---|
| Alonso-Ruiz et al [24] 13 RCTs |
RA (7087 pts in TNF + comparator gps) |
NA | NA | While on drug (duration of trial) |
6-24 months |
Etanercept Infliximab Adalimumab |
Placebo or Non Biologic DMARD |
OR (CI): 1.4 (0.8- 2.2) |
High doses of Infliximab associated with increased risk of serious infection p =0.006 |
| Leombruno 2009i 18 RCTs [25] |
RA 8808 subjects |
NA | NA | While on drug (duration of trial) |
3-18 months |
Etanercept Infliximab Adalimumab at recommended doses |
Placebo or Non Biologic DMARD |
OR (CI) 1.21(0.89-1.63), Exposure adjusted RR (CI) 1.07 (0.81-1.43) |
OR of infections with ETA was lower, however significance unknown |
| While on drug (duration of trial) |
3-18 months |
Infliximab Adalimumab at high doses |
Placebo or Non Biologic DMARD |
OR (CI) 2.07(1.31- 3.26), Exposure adjusted RR (CI) 1.99 (0.90-4.37) |
|||||
| Dommasch 2011 20 RCTs [26] |
Psoriasis, PsA 6810 patients |
NA | NA | Duration of trial | 12-30 wks |
Etanercept Infliximab Adalimumab Golimumab Certolizumab |
Placebo or non biologic DMARD |
OR (CI) 0.7 (0.4-1.21) |
NA |
| Thompson 2011 [27] 6 RCTs |
2183/1236 | Duration < 3 yrs HAQ 1.3-1.6 DAS data NA for 5/6 trials |
Hospitalized infections |
While on drug (duration of trial) |
At least 6 months |
Adalimumab or Etanercept or Golimumab or Certolizumab or Infliximab |
Non biologic DMARDs |
OR (CI) 1.28 (0.8-2.0) |
NA |
| Bongartz 2006 [28] 9 RCTs |
RA 5014 patients in TNF + comparator gp |
NA, described as heterogeneous in terms of disease duration and disease activity |
NA | While on drug (duration of trial) |
3-12 months |
Adalimumab, Infliximab |
Placebo or Non biologic DMARDs |
Pooled OR (CI) 2.0 (1.3-3.1) |
Similar results were observed b/n high dose and low dose TNF groups |
| Singh 2011 [29] 160 RCTs and 46 extension studies |
Any indication other than HIV: 60630 subjects |
NA | Infections leading to death, hospitalization or disability. Included bacterial infections and OIs in most studies |
While on drug (duration of study) |
RCTs: Median 6 months Ltes: 13 months |
5 Anti-TNF agents, Abatacept, Anakinra, Rituximab, Tocilizumab |
Placebo or Non Biologic DMARD |
All anti-TNF OR (CI) 1.41 (1.13-1.75) TNF Antibody 1.48 (1.15-1.90) TNF Receptor 1.17 (0.74-1.83) Eta 1.29 (0.72- 2.45) Inf 1.41 (0.75-2.62) Ada 1.23 (0.65- 2.4) |
Ada vs. Eta 0.78 (0.58-1.16) Inf vs. Eta 0.93 (0.6-1.42) Inf vs. Ada 1.19 (0.79-1.79) |
| Fleishmann 2006 [30] Pooled data from 22 Etanercept RCTs |
< 65 yrs: 3296 ≥ 65 yrs: 597 |
NA | Medically important infections: IV antibiotics or admission to hospital |
At least 1 dose of etanercept |
< 65: 5895 patient yrs, ≥ 65: 903 patient yrs |
Etanercept, age < 65 |
Etanercept, age ≥ 65 |
Medically important infections No significant difference b/n 2 gps |