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Effectiveness of Adalimumab in the Therapy of Paediatric Uveitis
Infliximab probably even 1+ – in CAU children is still a very good situation; this
In a prospective study, Saurenmann et al.
19
reported on the different is in contrast to some other types of uveitis, which were the basis of
responses to etanercept and infliximab in JIA-associated uveitis. the Standardization of Uveitis Nomenclature (SUN) criteria.
29
In this
Overall, there was a better response to infliximab than to etanercept regard the SUN criteria need some revision: response criteria for CAU
in reducing uveitis. The good response of uveitis to infliximab is should be defined depending on the underlying uveitis.
supported by several other reports.
20–23
Tynjälä et al. were the first to
report an exacerbation of uveitis while treating with infliximab. In Summary and Conclusions
their retrospective study with 24 patients taking etanercept and 21 In the ‘steroid’ era, there was general agreement among experts that
patients taking infliximab, inflammatory activity improved more achieving 0 cells in the anterior chamber of CAU children was generally
frequently in the infliximab-treated group.
24
Similar results have too difficult and that the prognosis in terms of the visual outcome might
been published by Galor et al.,
25
who compared etanercept and not be better. In the current era, new studies are needed regarding the
infliximab in 22 patients. All of the etanercept-treated patients had response criteria and the final end-point of an effective treatment.
to change medication to achieve control of ocular inflammation Because of the half-lives of the TNF-α-blocking drugs, we strongly
compared with only one patient in the infliximab group. recommend controlling children at different time-points in the interval of
application: the most reliable day for estimating the number of cells in
Adalimumab the anterior chamber is just before re-administration of the drug.
While the experience with adalimumab is limited in adults, there is
evidence for its effect in JIA-associated uveitis, substantiated by Further studies are needed to confirm that differences do exist between
three studies that published data on its effect in groups of 14–20 etanercept on the one hand and infliximab or adalimumab on the other
patients. Unfortunately, for paediatric uveitis there are no official hand in terms of their effect on uveitis. Both groups differ in terms of
criteria to define the efficiency of the drug, which was the major their binding characteristics, because infliximab and adalimumab bind
difference between these three studies. Our group recently to both soluble and membrane-bound TNF, while etanercept binds to
reported a retrospective trial of 18 patients with anterior uveitis, 17 soluble TNF only. Different effects on complement activation and
of whom had JIA-associated anterior uveitis.
26
All of the patients had apoptosis may result: infliximab may lyse in vitro TNF-producing cells via
been treated previously with at least two other immunosuppressive activation of complement, and seems to induce apoptosis of
drugs (MTX and cyclosporine A) in addition to oral corticosteroids, immunocompetent cells and monocytes. In addition, the different
with no effect. Adalimumab was effective – defined by no relapse pharmacokinetic behaviours of these three TNF inhibitors may influence
or at least two fewer relapses compared with the pre-treatment their effect on uveitis, and probably less so on arthritis. In particular, the
period – in 16 patients, mildly effective in one patient and not frequency of drug administration could be a very crucial point for the
effective in one patient. The median time to response was three treatment of these children.
weeks (range two to four weeks).
In conclusion, TNF-α blockers offer a very effective method of
Vazquez-Cobien et al. reported on 14 patients, of whom 13 showed treating JIA-associated uveitis that is refractory to second-line
a decrease in ocular inflammation on adalimumab,
27
defined as immunosuppressive therapy. Of the three drugs available, infliximab
“sustained decrease in anterior chamber cell count over two visits and adalimumab seem to have a better effect on reducing ocular
three months apart”. The median time to response was six weeks inflammatory activity. Because of its administration by subcutaneous
(range two to 12 weeks). All children had previously received at injection and its better side-effect profile, adalimumab may be the
least one immunosuppressive drug that had been ineffective in most favourable TNF-α-blocking agent, but prospective, randomised
treating uveitis. This study used weekly dosing instead of the trials are required to confirm this hypothesis. Unfortunately, signals
standard treatment of every other week. from industry indicate that there is only very limited interest in such
trials. Fortunately, adalimumab is now approved in the US for children
Recently, Tynjälä et al.
28
reported on 20 children, 18 of whom had with JIA, and approval in the European Medicines Agency (EMEA)
been treated with at least one other immunosuppressive and 95% of countries is expected within the next few months.
whom had previously been on infliximab. The mean duration of
adalimumab therapy was 18.7 months. Of the 20 patients, seven Regarding treatment with TNF-α-blocking agents, some important
(35%) showed improved activity and one (5%) showed worsening open questions remain:
activity, and in 12 patients (60%) no change was observed in
the activity of uveitis. Those with improved activity were younger and What is the risk of infection besides tuberculosis, and what is
had shorter disease duration. Inactive disease in this study was the risk of malignancies?
defined as 0 cells in the anterior chamber. For how long do the drugs have to be used?
What is the result of combining these drugs with immuno-
These reports, all resulting from highly selected, previously suppressive drugs in terms of increasing effectiveness and
adequately treated patients from tertiary care centres, show very reducing antibody production?
promising results for the use of adalimumab, since the side effects – How should ineffective treatment be handled: changing
such as injection-site reactions and the formation of neutralising regimen, reducing the treatment interval or adding other
antibodies – tend to be less frequent. The difference in the immunosuppressives?
improvement rate seems to be dependent on the different outcome Why do some children with chronic uveitis respond very well to
measurements. In our study we used the reduction of recurrences, etanercept while others do not?
defined as continuing increase of cells in the anterior chamber for Why do TNF-α blockers become ineffective after a certain period
some days. We strongly believe that a cell count of 0.5 – and of time (without autoantibody production), and why is it effective
EUROPEAN OPHTHALMIC REVIEW 87
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