A systematic review of the effectiveness of adalimumab

een quit on grounds of toxicity, adalimumab
monotherapy is given instead. In either case, this
therapy is followed by leflunomide. Option 4 is
similar to option 3, with etanercept instead of
adalimumab. In option 5, the combination
infliximab plus methotrexate is given immediately
after the divergence point.
In practice, patients who had quit methotrexate on
grounds of toxicity would not be given a
combination of infliximab and methotrexate
(option 5). It was assumed that such patients
would be given infliximab as single therapy,
although the authors recognise that infliximab is
often combined with other agents such as
leflunomide or azathioprine in clinical practice. It
was further assumed that the effectiveness of
infliximab without methotrexate in these
circumstances is similar to infliximab with
methotrexate. To compensate for a bias in favour
of infliximab introduced by this assumption, the
cost for the combination is also used. (The cost of
methotrexate forms only a small part of the cost of
this combination.) Thus, in the model, the data set
TABLE 37 Strategy set with TNF inhibitors as last active therapy
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Health Technology Assessment 2006; Vol. 10: No. 42
for the combination infliximab plus methotrexate
is used regardless of the reason for quitting
methotrexate. Option 5 continues with
leflunomide, and so on. Finally, option 6 involves
the use of leflunomide immediately after the
divergence point. Differences between options are
stored and the process is repeated for a sufficiently
large number of patients.
Single TNF inhibitors as last active therapy In this
strategy set, patients are run through the whole of
the baseline strategy if necessary. Any patient who
dies while still on active therapy is discarded from
the analysis and replaced by a new patient. Any
patient who fails on all the conventional DMARDs
used in the baseline strategy reaches the divergence
point (see Table 37, options at the divergence point
are shaded). Thus, in this strategy TNF inhibitors
are used are treatments of last resort. As before, the
patient’s characteristics at the divergence point are
stored before the patient starts on option 1
(adalimumab followed by palliation). The patient is
then restarted from the divergence point and run
through each of the other options.
Moves dependent on toxicity
Treatment Always move to Relevant toxicity If toxic, move to Otherwise, move to
MTX MTX SSZ MTX+SSZ
SSZ LEF
MTX+SSZ MTX+SSZ LEF MTX+SSZ+HCQ
MTX+SSZ+HCQ LEF
LEF GST
GST AZA
AZA CyA
CyA CyA or MTX DPEN CyA+MTX
CYA+MTX DPen
DPen Divergence point
Option 1 Adal
Adal Pall
Option 2 Etan
Etan Pall
Option 3 MTX Adal Adal+MTX
Adal+MTX Pall
Option 4 MTX Etan Etan+MTX
Etan+MTX Pall
Option 5 Infl+MTX a
Infl+MTX Pall
Option 6 Pall
a The data set for this combination is used in the model, regardless of the reason for quitting MTX.
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