Table 2.
Adverse events related to different anti-tumour necrosis factor agents used in juvenile idiopathic arthritis (data mainly from long-term studies and biologics registries)
| References | Etanercept | Adalimumab | Infliximab | ||||||
|---|---|---|---|---|---|---|---|---|---|
| 18 | 26 | 29 | 19 | 28 | 27 | 44* | 29 | 72 | |
| No. of patients | 61 | 58 | 95 | 146 | 397 | 604 | 171 | 68 | 78 |
| Median/mean exposure (years) | 1.1 | NA | 2.0 | 2.5 | NA | NA | NA | 1.8 | 2.2 |
| Maximal exposure (years) | 2.5 | 8 | 5.9 | 7.3 | 3 | NA | 2 | 6.1 | 3.9 |
| Cumulative patient-years of exposure | NA | 318 | 258 | 312 | 859 | 1149 | 319.3 | 140 | NA |
| No. of adverse events | 68 | NA | 133 | 65 | 179 | 190 | 2549 | 71 | 71 |
| No. of serious adverse events | NA | 39 | NA | 9 | NA† | 52 | 17 | NA | 17 |
| Anaphylactoid/serious drug reactions (%) | 0 | 0 | NA | 0 | 0 | 0 | 0 | 1.5 | 3.6 |
| Serious infections (%) | NA | 15.5 | 3.2 | 2.7 | 2.8 | 4.3 | 4.1 | 1.5 | 2.6 |
| Opportunistic infections (%) | NA | 0 | 0 | 0 | NA | 0.2 | 0 | 0 | 0 |
| New auto-antibody development (%) | 20.6 | NA | 2.1 | NA | 3.8 | NA | NA | 10.3 | 32.5 |
| New/worsening uveitis (%) | 2.9 | 0 | 4.2 | 0 | 0.3 | 1.5 | 0 | 4.2 | 5.0 |
| Demyelinating events (%) | 1.5 | 0 | 0 | 0 | 0 | 0.3 | 0 | 0 | 0 |
| Malignancies (%) | 0 | 0 | 1‡ | 0 | 0 | 0.5§ | 0 | 0 | 0 |
| Deaths | 0 | 0 | 0 | 0¶ | 0 | 0 | 0 | 0 | 2.6** |
Abbreviation: NA, not applicable.
Safety data available from the original clinical trial to date.
This study compared patients on methotrexate, etanercept and etanercept plus methotrexate, and found the exposure-adjusted rates of serious adverse events per 100 patient-years to be 4.6, 7.1 and 6.0, respectively, but the study did not provide the absolute number of serious adverse events.
One case of malignancy (thyroid cancer).
Three cases of malignancy (thyroid carcinoma, yolk-sac carcinoma, non-Hodgkin's lymphoma).
Three nonresponders to etanercept subsequently died of tuberculosis, suspected macrophage activation syndrome and sepsis whilst on other immunosuppressives, at least 8 months after etanercept discontinuation.
The first died at week 2 of the trial, 10 days after a placebo infusion, from septic shock and an associated deterioration in cardiac function; the second patient had systemic-onset juvenile idiopathic arthritis, experienced a severe flare of their disease and died of a cardiac arrest 3 months after discontinuation of infliximab (in the 3 mg kg−1 infliximab group), whilst in the open-label extension phase of the study.