A systematic review of the effectiveness of adalimumab

TABLE 44 Early cessation of DMARDs: data, sources and comments (cont’d)
Drug Cessation at Ceasing between Comments and source
≤ 6 weeks a 6 and 24 weeks
for toxicity. The second step represents cessation
between 6 and 24 weeks after starting treatment,
which could be for toxicity or inefficacy. Table 44
shows the data used for early cessation of DMARDs.
The implementation of this approach is illustrated
in Figure 49. The variables u1 and u2 are drawn
from a uniform distribution between 0 and 1. The
value of u1 is used primarily to determine the
HAQ improvement on starting treatment using
the beta distribution with parameters as shown in
Table 43, while u2 determines the time on
treatment. The four zones in Figure 49 represent
the following:
A withdrawal within 6 weeks (assumed due to
toxicity)
B withdrawal between 6 and 24 weeks for inefficacy
C withdrawal between 6 and 24 weeks for toxicity
D remaining on the treatment after 24 weeks.
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Health Technology Assessment 2006; Vol. 10: No. 42
DPen Assume same as AZA No reliable data are available for use of penicillamine late
in disease; late drug-use data are required by the modelling
strategy
SSZ 10% 28% (9% because of No ideal source identified. Data estimated from two
toxicity, 10.5% for clinical trials (Proudman 187 and Smolen179 ) that gave data
inefficacy and 8.5% for from which inferences about early and late cessations were
other reasons) made
Combination 0% 50% No data source. The model assumes that patients will have
(CyA and MTX) tried both MTX and CyA monotherapy before trying this
combination. Therefore, patients experiencing toxicity to
either agent in the past would not be eligible for this
combination. The use of this combination after failed
monotherapy with CyA and MTX assumes a synergistic
effect for efficacy, although there is no definitive evidence
for this. In the absence of data, but based on an educated
guess, it was assumed that 50% of patients cease therapy
after 24 weeks owing to lack of efficacy
Combination As for SSZ As the model does not propose combination therapy from
(MTX and SSZ) the outset with this combination, but proposes that SSZ is
added when MTX is inefficacious (and not toxic), in a stepup
strategy, it was assumed that patients respond, in terms
of toxicity and drug continuation, as they would if SSZ
alone had been used
Combination As for HCQ As above, the model does not propose combination
(MTX, SSZ therapy from the outset but drugs are added in a step-up
and HCQ) strategy. Thus, toxicity and drug continuation rates for this
combination are assumed to be similar to HCQ alone,
since patients only use HCQ in the combination if MTX
and SSZ in combination have been inefficacious (and not
toxic)
a It is assumed, unless stated otherwise, that patients ceasing by 6 weeks do so because of drug toxicity.
u1
0
1
A
0 1
u2
B
C D
FIGURE 49 Early cessation of treatment
97