A systematic review of the effectiveness of adalimumab

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FIGURE 46 Basic structure of the model
Strategies compared using the BRAM
Baseline for comparison
Before considering how TNF inhibitors could be
included in treatment strategies, it is convenient to
describe the baseline strategy without TNF
inhibitors.
The baseline strategy, based on a survey of
rheumatology consultants in the UK, 25 starts with
methotrexate as single therapy. If methotrexate is
stopped on grounds of toxicity, it is followed by
sulfasalazine as single therapy, otherwise by the
combination of methotrexate plus sulfasalazine.
Similarly, if this combination is quit on grounds of
toxicity, it is followed by leflunomide. But, if the
methotrexate–sulfasalazine combination lacks
efficacy, hydroxychloroquine is added to the
combination. These rules are shown in Table 34
under the heading ‘Moves dependent on toxicity’.
For most other treatments, the choice of treatment
next in sequence, and the move to the next agent,
simply depend on drug cessation, for whatever
reason. For example, sulfasalazine as single therapy,
in Table 34, is always followed by leflunomide, as
shown under the heading ‘Always move to’. In the
case of ciclosporin, the preferred next treatment is
the combination of ciclosporin plus methotrexate.
However, this combination cannot be offered if
ciclosporin has just been quit on grounds of
toxicity, nor can it be offered if methotrexate was
earlier quit for toxicity. This is shown under
HAQ increase
Death
Event taking no time
Activity taking a variable
amount of time
‘Relevant toxicity’. Palliation is the treatment of last
resort and therefore cannot be quit.
The structure as shown in Table 34 is more general
than the structure used in previous versions of the
BRAM: all the previous strategies in the model
can be described by tables of this form.
Comparisons
For clarity, the word ‘comparison’ is reserved for
an analysis comparing two options. The term
‘strategy set’ is used for a collection of strategies
(treatment sequences) with a common initial
sequence and divergence point.
Single TNF inhibitors (versus no TNF inhibitor)
In these strategy sets only one TNF inhibitor is
used. There are six options in each case:
adalimumab alone; etanercept alone; each of the
three TNF inhibitors combined with methotrexate;
and the comparator option without TNF inhibitors.
These produce a total of 15 possible comparisons:
five (‘major comparisons’) relate to including each
TNF inhibitor singly within a sequence without
TNF inhibitors and ten (‘minor comparisons’) relate
to comparisons between different TNF inhibitors.
Single TNF inhibitor at the start In this strategy set,
the divergence point is at the start of the
sequence, that is, patients are treated with a TNF
inhibitor before any other DMARD (see Table 35,