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Transcript of Effective and sustainable biologic treatment of psoriasis: what can we learn from new clinical data?
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REVIEW ARTICLE
Effective and sustainable biologic treatment of psoriasis:what can we learn from new clinical data?
R.G. Langley*
Queen Elizabeth II Health Sciences Centre, Division of Dermatology, Department of Medicine, Dalhousie University, Halifax,
Canada
*Correspondence: R. Langley. E-mail: [email protected]
AbstractThe introduction of the biologic agents, adalimumab, etanercept, infliximab and ustekinumab, has provided more
options for the short- and long-term treatment of patients with psoriasis. Physicians are now able to achieve and
maintain effective disease control in more patients using biologic therapies. Newly published clinical data support
the introduction of novel optimization strategies to further improve outcomes in patients with psoriasis. Recent
randomized controlled clinical trials have provided data on the efficacy of conventional therapies, including systemic
agents, and biologics at specific time points. Switching from methotrexate to a tumour necrosis factor (TNF)-a
antagonist after 16 weeks can improve response rates, as demonstrated in a study of patients with moderate-to-
severe psoriasis, while the benefit of long-term methotrexate use remains unclear. In a separate study, psoriasis
area and severity index (PASI) 75 response rates were maintained over time (>3 years for adalimumab), suggestingthat long-term biologic therapy is an effective and sustainable treatment option for psoriasis. For each individual
patient, the benefit of a particular treatment needs to be balanced with the risks. The lack of head-to-head trials of
antipsoriatic therapies, particularly biologic therapies, does not help with making individualized treatment decisions.
However, a benefitrisk assessment of TNF-a antagonists calculated from an integrated analysis of published
literature in moderate-to-severe psoriasis can be used to aid clinical practice. The number needed to treat, number
needed to harm and number of patient years of observation to detect an adverse event have been determined for
adalimumab, etanercept and infliximab. The benefitrisk profiles generated demonstrated that, during the initial year
of treatment, likelihood of success with TNF-a antagonists was several orders of magnitude greater than the
likelihood of serious toxicity.
Received: 22 November 2011; Accepted: 28 November 2011
Conflicts of interestR.G.L. has served as consultant and or paid speaker for and or participated in clinical trials sponsored bycompanies that manufacture drugs used for the treatment of psoriasis including Abbott, Amgen, Astellas, Boehringer
Ingelheim, Celgene, Centocor, Genentech, Merck, Novartis and Pfizer.
Funding statementThe writing of this supplement article was sponsored by an educational grant from Abbott Immunology.
IntroductionThe development of biologic therapies has provided dermatolo-
gists with an increasing repertoire of treatments with which to
treat psoriasis, in both the short- and long-term. Biologic thera-
pies fall into two main categories: the tumour necrosis factor-a(TNF-a) antagonists and interleukin (IL)-12 23 monoclonal anti-bodies (mAbs). TNF-a antagonists (adalimumab, etanercept andinfliximab) block the binding of TNF-a to its receptor, interrupt-ing the subsequent signalling and inflammatory pathways driven
by TNF-a. This suppresses inflammation and the increased activa-tion of T cells that are characteristic of psoriasis. IL-12 23 mAbs
(ustekinumab) inhibit the activity of IL-12 and IL-23, cytokines
that drive the inflammatory processes which can cause psoriatic
lesions.
Several randomized controlled clinical trials have demonstrated
the efficacy of biologic therapies in the first year of psoriasis
treatment.111 A summary of the key outcomes of these trials is
provided in Table 1. The TNF-a antagonists (adalimumab, etaner-cept and infliximab) and ustekinumab provide efficacious therapy,
with high rates of psoriasis area and severity index (PASI) 75
response being achieved by patients in all trials. These trials also
illustrated the safety and tolerability of biologic therapies,
2012 The AuthorJEADV 2012, 26 (Suppl. 2), 2129 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
DOI: 10.1111/j.1468-3083.2011.04412.x JEADV
-
during these periods, an important concept when considering
treatment decisions.
Role of conventional systemic therapies
Despite the encouraging results seen in response to biologic thera-
pies, conventional treatments continue to play a major role in der-
matology and should still be considered for use in patients with
psoriasis. As psoriasis is a chronic disease, long-term maintenance
requires continued use of therapy. Systemic therapies have been in
use for decades and are well established in treatment regimens,
and dermatologists are better positioned to make long-term deci-
sions on the use of such conventional therapies. For example,
methotrexate has been successfully used for the treatment of psori-
asis since the 1950s.12,13 Methotrexate has been combined with
Table 1 Results of pivotal randomized controlled clinical trials of biologic therapies for the treatment of psoriasis
Treatment schedule Number of patientsreceiving biologictherapy
PASI 75 responserate (%) at1016 weeks*
Complete ornear-completeclearance (%)
Adalimumab
CHAMPION1 80 mg at week 0 then 40 mg e.o.w.from week 1
108 79.6 16.7 (PASI 100)
51.3 (PASI 90)
73.1 (PGA 0 1)REVEAL2 80 mg at week 0 then 40 mg e.o.w.
from week 1814 71 20 (PASI 100)
45 (PASI 90)
60 (PGA 0 1)BELIEVE3 80 mg at week 0 then 40 mg e.o.w.
from week 1364 70.9 24.2 (PASI 100)
50.8 (PASI 90)
64.4 (PGA 0 1)Gordon et al.7 80 mg at weeks 0, 1; then 40 mg q.w. 50 80 26 (PASI 100)
33 (PASI 90)
76 (PGA 0 1)Etanercept
Leonardi et al.4 50 mg b.i.w. 164 49 22 (PASI 90)
49 (PGA 0 1)Papp et al.5 50 mg b.i.w. 194 49 21 (PASI 90)
57 (PGA 0 1)Tyring et al.45 50 mg b.i.w. 311 47 21 (PASI 90)
Gottlieb et al.46 25 mg b.i.w. 57 30 >50 (PGA 0 1)van de Kerkhof et al.47 50 mg q.w. 37.5 64 (PGA 0 1)Infliximab
EXPRESS 18 5 mg kg at weeks 0, 2, 6; then every 8 weeks 301 80 57 (PASI 90)83 (PGA 0 1)
EXPRESS 29 5 mg kg at weeks 0, 2, 6 314 75.5 45.2 (PASI 90)76.0 (PGA 0 1)
Ustekinumab
PHOENIX 110 45 mg at weeks 0, 4; then every 12 weeks 255 67.1 12.5 (PASI 100)
41.6 (PASI 90)
60.4 (PGA 0 1)90 mg at weeks 0, 4; then every 12 weeks 256 66.4 10.9 (PASI 100)
36.7 (PASI 90)
61.7 (PGA 0 1)PHOENIX 211 45 mg at weeks 0, 4; then every 12 weeks 409 66.7 18.1 (PASI 100)
42.3 (PASI 90)
68.0 (PGA 0 1)90 mg at weeks 0, 4; then every 12 weeks 411 75.5 18.2 (PASI 100)
50.9 (PASI 90)
73.5 (PGA 0 1)
*These trials were not conducted in a head-to-head fashion and differing methods of statistical anaysis and study designs do not make comparisons
possible.
b.i.w., twice per week; e.o.w., every other week; PASI, psoriasis area and severity index; PGA, physicians global assessment; q.w., once per week.
2012 The AuthorJEADV 2012, 26 (Suppl. 2), 2129 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
22 Langley
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psoralen and ultraviolet A (PUVA), ultraviolet B (UVB), etretinate
and cyclosporine with the aim of improving efficacy, reducing
dosage and limiting associated toxicity.1421 Methotrexate and
cyclosporine have been particularly successful in achieving this,
although long-term use has not been reported.21 The efficacy of
cyclosporine in the treatment of psoriasis has been investigated
and established in randomized controlled trials (RCTs). These
studies have been of short duration and the approved use of this
agent in most countries is for a limited period due to concerns
over toxicity.2227 However, short intermittent courses of cyclo-
sporine are effective and have been adopted in clinical practice.25,26
Retinoids are a group of natural and synthetic therapies closely
related to vitamin A. They are also well established in the treat-
ment of dermatological conditions: acitretin, an oral retinoid, is
currently used for moderate-to-severe psoriasis.28 Despite these
agents being in use for over 50 years, there are few RCTs that
address the dosing and treatment regimen of retinoids.2932 The
combination of retinoids with topical or phototherapies has
proved effective for psoriasis treatment and can be more successful
than retinoid monotherapy.3338
Conventional systemic agents remain important therapies in the
management of patients with psoriasis. The use of conventional
therapies, however, must be monitored regularly and modified if
the treatment goal is not reached.39 For treatment to achieve maxi-
mal benefit and optimal patient outcomes, it must be initiated
and modified in a timely and appropriate manner. Although RCTs
continue to demonstrate the efficacy and safety of biologic thera-
pies, there has been less systematic investigation regarding conven-
tional therapies. Despite the proven efficacy and safety of biologic
agents in the treatment of psoriasis, there appears to be a general
reluctance among dermatologists to prescribe them.40 This article
aims to address this discrepancy and provide evidence for the
effective and sustainable use of biologics in psoriasis.
Optimization strategies for systemic and biologictherapiesOptimizing results with systemic or biologic agents may enhance
the efficacy achieved with these agents. It is important to be aware
of what responses may be expected and when efficacy may be
observed. Specific guidelines have been developed which summa-
rize this information and can assist clinicians in the decision to
switch or modify treatment regimens, as appropriate.39 As new
treatments are introduced, it is important that dermatologists are
aware of the best use of therapies through the analysis of evidence-
based clinical data. Recent clinical studies have investigated opti-
mization strategies to define such areas, and these are reviewed
below.
Optimization of conventional therapies
Conventional therapies range in their probability of achieving an
adequate clinical response and in the level of efficacy attained.41,42
Methotrexate provides an example of a drug that is well estab-
lished in the treatment of psoriasis, but lacks an evidence-based
approach to optimizing dose. The lack of evidence-based strategies
has, in part, led to an experience-based approach, with a subse-
quent lack of standardized, evidence-based treatment guidelines,
which has contributed to a large variety of treatment regimens.
Three recent Phase 3 clinical trials have been performed in
which methotrexate was compared with biologic agents.1,43,44 The
initial trial, CHAMPION, randomized 271 patients to receive ada-
limumab, methotrexate or placebo for 16 weeks.1 RESTORE ran-
domized 868 patients to receive infliximab or methotrexate for
16 weeks, after which treatment switch was permitted.44 A third
Phase 3 trial randomized 317 patients to receive briakinumab or
methotrexate over 52 weeks (M10-255).43 RESTORE and M10-
255 indicated that if a PASI 75 response is not achieved by week
16, then it is not likely to occur and treatment discontinuation or
modification should be considered.43,44 Switching from metho-
trexate to a TNF-a antagonist after 16 weeks can improve theresponse.44 In CHAMPION, the methotrexate dose was started at
7.5 mg orally and sequentially increased in subsequent weeks,
depending on clinical response and the presence of adverse
events.1 The methotrexate dose was increased to 20 mg week ifPASI 50 response had not been reached by week 8 and it was fur-
ther increased to 25 mg week if PASI 50 had not been reached byweek 12. Results at week 16 showed that PASI 75 was achieved by
79.6% of patients who received adalimumab, compared with
35.5% of patients who received methotrexate. Conclusions drawn
from this information are limited because methotrexate was
started and maintained at a relatively low dose compared with
clinical practice and dose increases were not appropriate in the
achievement of a high PASI response (only increased if response
was
-
trexate had a PASI 75 response. The results from this trial demon-
strate the benefit of appropriate dose escalation of oral methotrex-
ate until 20 mg week. Patients with a sub-optimal response at thisstage receive little further benefit from increasing the dose to
25 mg.43 This response-guided therapeutic approach increasingly
reflects current practice, as depicted by the European Consensus
Programme on goals for the treatment of psoriasis, and shows the
importance of regular monitoring.39
Optimization of biologic therapies
The expected short-term efficacy of different biologic agents has
been described in several RCTs15,711,4547 and the European goals
were recently set out by the European Consensus Programme.39
Patients who have not achieved an adequate response by a defined
endpoint may be considered primary failures. Patients who reach
a specified endpoint but who then lose response are considered
secondary failures.48 Following primary or secondary failure, it is
important to clinically address why these patients failed to respond
or lost response. Factors which may be considered include adher-
ence compliance, confounding factors (infection, natural variationin disease, exogenous stress) or inadequate drug levels. Before dose
optimization, it is crucial to determine whether any of these con-
founding factors led to primary or secondary failure. In the
absence of a confounding variable that would explain failure to
achieve an immediate response (primary) or later response (sec-
ondary), clinicians can attempt to optimize therapy.
The long-term use of biologic therapy was addressed in the
Phase 3 REVEAL trial, which examined the extended efficacy and
safety of adalimumab. Following the initial 52-week trial period,
patients were able to enter an open-label extension trial to receive
adalimumab for a total of 3 years. The PASI response rates
achieved by patients treated with adalimumab were compared
with patients who received placebo.49 During the initial Phase 3
trial, 71% patients who received adalimumab achieved PASI 75
response. Approximately 60% of patients who entered the ada-
limumab arm became sustained responders, achieving a PASI 75
response at weeks 16 and 33. At 100 weeks and 160 weeks of con-
tinuous therapy, PASI 75 was retained by 83% and 76% of these
initial responders, respectively. Some patients with
-
40 mg week), infliximab (from a dose every 8 weeks to a doseevery 6 weeks) and ustekinumab (45 or 90 mg every 12 weeks to
45 or 90 mg every 8 weeks). To ensure the optimal efficacy of ada-
limumab, it is important to include an induction dose of 80 mg at
baseline. A recent study has shown that failing to provide this
loading dose can result in inferior efficacy and is less cost-effec-
tive.50 A small study has shown that increasing infliximab dose
beyond 5 mg does not improve the efficacy; rather, shortening the
time between dose intervals may be a more appropriate modifica-
tion.51
Weight is an important factor for consideration when making
therapeutic decisions in the use of biologic agents. A study that
examined the effect of weight on the efficacy of biologic therapy
showed that weight-based regimens do not result in reduced effi-
cacy in heavier patients.52 An analysis of the PHOENIX trials
investigated how the optimal dose of ustekinumab is affected by
weight. The study analysed weight in 10 kg increments and found
that weight-based fixed dosing gives improved efficacy to patients.
This study is potentially limited by a cut-off of 100 kg, which may
not be reflected in clinical practice.53 A comparison of week 12
data by weight was carried out using data from two clinical trials
of adalimumab and one of etanercept. Patients were divided into
100 kg groups. The adjusted outcome showed that
both drugs have a reduced efficacy in heavier patients.54
Modification and transitioning of therapies
Novel optimization strategies can provide a standardized basis for
the development of patient treatment, ensuring that the most ben-
eficial outcomes can be reached. The modification of treatment is
crucial to achieving the treatment goal following initial failure.
The transitioning of treatments may take a number of forms,
including direct switching to a new therapy and the overlap or
temporary permanent addition of a new therapy. The successfultransitioning from methotrexate to biologic therapy has been
demonstrated in other clinical trials.44,55
Efficacy may also be achieved with the use of concomitant ther-
apy. Topicals such as corticosteroids, calcipotriene and other
agents (i.e. coal tar, anthralin) may be used as monotherapy or
combination therapy [for example, betamethasone and calcipotriol
(Dovobet)] in psoriasis treatment. Topical therapy is usually the
initial therapy used in psoriasis treatment and can be added to
biologic therapies to optimize results.56 Acitretin is a retinoid that
may be combined with biologic agents to increase efficacy and
reduce side-effects compared with retinoid monotherapy, includ-
ing a possible reduction in the risk of skin cancer.57,58
Combined treatment with topical therapies and biologic agents
can be used in clinical practice and may serve to maximize thera-
peutic outcome. The BELIEVE study compared the efficacy of
adalimumab in combination with a topical versus adalimumab
with vehicle only. After 4 weeks of therapy, PASI 75 rate was
achieved by 40.7% versus 32.4% in the adalimumab + topical
group compared with the adalimumab + vehicle group, respec-
tively. This demonstrated that a rapid and higher efficacy was
achieved with the combination therapy within the first 4 weeks of
treatment. This was not sustained: by 16 weeks, 64.8% and 70.9%
of patients receiving combination treatment compared with ada-
limumab + vehicle, respectively, had achieved a PASI 75
response.3 However, after 4 weeks of treatment, the use of topical
therapy changed from once daily to as required, and this may
have introduced adherence as a confounding factor in the inter-
pretation of these data.
Methotrexate has been utilized in combination with TNF-aantagonists routinely in the management of psoriatic arthritis and
rheumatoid arthritis.5961 More recently, the systemic agent has
been combined with biologics in the treatment of psoriasis. The
NORDIC study compared a combination of etanercept with con-
tinuous methotrexate versus etanercept with tapered and discon-
tinued methotrexate in patients with psoriasis. Significantly more
patients achieved a physicians global assessment score of clear al-most clear in the continuous therapy group compared with the
methotrexate tapered group (66.7% versus 37.0%, respectively).62
This was supported by data from a more recent larger, random-
ized, double-blind, placebo-controlled Phase 3b study that com-
pared the responses of patients who received methotrexate and
etanercept compared with etanercept alone. After 24 weeks of
treatment, significantly more patients receiving combination treat-
ment achieved PASI 50, 75 and 90 responses compared with those
receiving etanercept monotherapy.55
Benefitrisk profiles of biologic therapiesIn making treatment decisions, there may be a tendency for per-
sonal experiences or perception of riskbenefit to positively or
negatively influence the use of therapies. There may be some con-
flict between evidence-based data and the personal preferences of
the dermatologist and or patient. Treatment guidelines and goalsare designed to facilitate such decisions, and the benefitrisk pro-
files of therapies provide dermatologists with important and acces-
sible information regarding therapy options and outcomes.
In the absence of head-to-head trials comparing the safety and
efficacy of different TNF-a antagonists, a benefitrisk assessmentof agents based on published data can be used to aid clinical deci-
sions. This may come from RCTs, postmarketing data or registry
data. Clinical trials provide high quality data but are often based
on short-term use of treatments and may not reflect clinical prac-
tice. There can be caveats to consider when analysing longer-term
studies with methodological shortcomings, the optimization of
treatments and criteria for patient inclusion, as well as methods of
statistical analysis. Postmarketing data can provide access to large
numbers of patients, but may not be high quality and do not
include controls. Registries are an important source of data,
providing long-term information on large numbers of patients,
although information from psoriasis-specific registries is limited.
When assessing benefitrisk profiles, one approach considers
the number of patients needed to treat (NNT) and number of
2012 The AuthorJEADV 2012, 26 (Suppl. 2), 2129 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Effective, sustainable biologic treatment of psoriasis 25
-
patients needed to harm (NNH), together with the number of
patient years of observation required before the detection of an
adverse outcome. The NNT is a measure used to determine the
efficacy of a given therapy defining the number of patients who
need to receive the assessed treatment for one benefit to be
observed, compared with a control group. The NNH is a measure
of how many patients need to be exposed to a risk factor over a
specified time frame in order for one patient to experience harm
that would not otherwise have occurred. Such analyses are based
on published data from trials of psoriatic treatments
(Table 2).63,64
A meta-analysis and literature review of 22 trials that compared
the efficacy of psoriasis treatments showed that TNF-a antagonistswere most likely to achieve a PASI 75 response. The relative risk of
achieving a PASI 75 response for TNF-a antagonists was 15.57,compared with 9.24 and 5.65 for systemic and T-cell therapies,
respectively.41 A comparison of the benefits and risks of TNF-aantagonists is shown in Table 3.
Another meta-analysis comparing TNF-a antagonists and sys-temic therapies used in the treatment of moderate-to-severe psori-
asis also demonstrated the high efficacy and tolerability of TNF-aantagonists. Low rates of adverse events were seen in patients
receiving TNF-a antagonists, and these were comparable to equiv-alent rates observed in patients on systemic therapies (Table 4).63
Due to their mode of action, there is concern that patients
receiving TNF-a antagonists may become more susceptible toinfection. This is an issue that may restrict the use of biologic
therapy but, in so doing, limit the potential for optimal patient
outcome. The meta-analysis of trial data of TNF-a antagonistsshowed low serious infection rates among patients on biologic
therapy (Fig. 2). The rates of infection ranged from 0.1 to 1.0% of
patients across the trials, compared with 0 to 0.9% of patients in
the placebo groups.64 An analysis comparing serious adverse
events across different indications of adalimumab indicated that
these are particularly low when compared with the equivalent
infection rates exhibited by patients who received adalimumab for
rheumatoid arthritis. The rates of serious infection in this analysis
were nearly three times greater in patients being treated for rheu-
matoid arthritis than in those treated for psoriasis (4.65 versus
1.32, respectively).65 Although such data may have raised concerns
among dermatologists regarding the use of biologics, these patient
groups cannot be compared directly because patients with rheu-
matoid arthritis may have different co-morbidities, and commonly
receive multiple therapies, including steroids, which have an
impact on their susceptibility to infection. The best predictors of
serious infection events for patients with rheumatoid arthritis can
include the severity of rheumatoid arthritis or the disease activity,
the use of corticosteroid therapy, the presence of co-morbidities
and the presence of skin infection and joint surgery.66,67 The use
of biologics should also be taken into consideration. These predic-
tors are useful indicators for physicians in controlling infection,
and similar parameters may prove useful for the treatment of pso-
riasis with biologic therapies.
Essentially, the benefitrisk profiles generated for antiTNF-atherapies demonstrate a benefit to patients in the first year of
treatment that greatly outweighs the risk of serious toxicity.64 This
is an important message that must be appropriately conveyed to
patients when discussing treatment options. The risk of developing
adverse events, including infection, is low.
ConclusionsConventional therapies remain important treatment options for
patients with psoriasis. They continue to play a central role in
developing therapy regimens, whether alone or in combination
with biologic treatments. The advent of biologics has provided
new options for dermatologists and patients with psoriasis. These
therapies have been extensively studied in RCTs and show high
efficacy rates as monotherapy in the majority of patients.64
Although biologic therapies have shown high efficacy, in certain
patients, optimization of therapy may be required to achieve an
initial response or regain disease control when response has been
lost. To optimize patient outcomes, it is vital to monitor the effec-
tiveness of treatment and modify the dose or therapy as appropri-
ate. Before optimizing treatment, it is important that any
confounding factors are addressed and that patients are assessed
with a careful history and clinical exam. Understanding new clini-
cal data and guidelines may facilitate optimal patient management,
in addition to enabling timely and appropriate decisions to be
made with regard to treatment modification and switching. Opti-
mization strategies can include an increase of dose, a decrease in
dose interval, or modification of the treatment regimen to include
a conventional topical or systemic agent.
The rates of adverse events are low for conventional psoriatic
treatments, including those for biologic therapies. The high effi-
Table 2 An evidence-based comparison from clinical trials: number of patients needed to treat with a specified biologic agent tosee a benefit compared with patients in a control group.64
Drug Dose Treated patientswho achievedPASI 75 (%)
Placebo patientswho achievedPASI 75 (%)
Number needed totreat (95%confidence interval)
Adalimumab 80 mg at week 0 then 40 mg e.o.w. for 16 weeks 72.1 8.0 1.6 (1.51.7)
Etanercept 50 mg b.i.w. for 12 weeks 48.4 4.1 2.3 (2.12.5)
Infliximab 5 mg kg at weeks 0, 2, 6; then every 8 weeks to 24 weeks 75.4 3.9 1.4 (1.31.5)
b.i.w., twice per week; e.o.w., every other week.
2012 The AuthorJEADV 2012, 26 (Suppl. 2), 2129 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
26 Langley
-
cacy demonstrated by biologic therapies greatly outweighs the low
risk of experiencing adverse events. The risks and side effects asso-
ciated with treatment are an important consideration and should
be taken into account when defining therapeutic strategies. The
benefitrisk profile of biologic therapies favours the appropriate
use of biologics for the treatment of moderate-to-severe psoriasis,
and effective disease control can now be achieved and maintained
through the appropriate use of such therapies.
AcknowledgementsThe author would like to thank Facilitate Ltd, funded by Abbott
Immunology, for editorial assistance in the production of this
manuscript.
References1 Saurat JH, Stingl G, Dubertret L et al. Efficacy and safety results from
the randomized controlled comparative study of adalimumab vs.
Table 4 Adverse event rates from a meta-analysis of 16double-blind, placebo-controlled trials that were reviewed for
treatment efficacy and tolerability63
DrugNumber ofstudies
Number ofpatients
Adverseevents*,%
Seriousadverseevents*,%
Cyclosporine2.55 mg kg
3 318 16.1 (n = 503) 2.3
Methotrexate15 mg q.w.
1 43 17.7 0
Infliximab5 mg kg
3 711 17.8 1.1
Etanercept50 mg b.i.w.
1 311 17.6 0.6
Adalimumab80 mg at week 0then 40 mg e.o.w.
1 814 16.6 0.5
*Average monthly incidence rate.
b.i.w., twice per week; e.o.w., every other week; q.w., once per week.
Figure 2 A comparison of serious infection rates from a meta-analysis of patients with psoriasis who received different TNF-aantagonist therapies. Point estimates for the NNHs, with 95% CIlower (NNH 2.5) and upper (NNH 97.5) bounds are provided.64
b.i.w., twice per week; e.o.w., every other week; NNH, number
needed to harm; q.w., once per week.
Ta
ble
3AcomparisonofbenefitriskprofilesofTNF-a
antagonists
64
Ad
alim
um
ab
1,2
,7E
tan
erc
ep
t4,5
,4547,6
8,6
9In
flix
ima
b8,9
Ad
alim
um
ab
*(n
=921)
Pla
ce
bo
(n=
451)
Eta
ne
rce
pt
(n=
511)
Pla
ce
bo
(n=
460)
Eta
ne
rce
pt
(n=
669)
Pla
ce
bo
(n=
665)
Infl
ixim
ab
(n
=301)
Pla
ce
bo
(n=
77)
Infl
ixim
ab
(n
=314)
Pla
ce
bo
(n=
208)
Ben
efiteffica
cyprofile
PASI75,%
72.1
8.0
34.2
3.0
48.4
4.1
75.4
3.9
75.5
1.9
PASI90,%
45.8
2.9
11.5
0.7
21.1
0.9
53.5
1.3
45.2
0.5
PASI100,%
19.7
0.9
NA
NA
NA
NA
NA
NA
NA
NA
Riskad
verseev
entprofile
AE
63.6
58.5
56.0
(n=415)
51.0
(n=414)
47.5
(n=670)
48.3
(n=270)
82.0
(n=298)
71.0
(n=76)
68.8
56.0
(n=207)
AEleadingto
discontinuation,%
1.6
2.2
2.3
2.8
1.2
2.1
9.1
6.6
5.1
2.4
SeriousAE,%
1.8
1.8
2.1
(n=96)
6.5
(n=46)
NA
NA
5.7
2.6
2.9
2.4
Seriousnon-infectiousAE,%
1.3
0.9
1.6
1.5
1.5
1.0
NA
NA
NA
NA
SeriousinfectiousAE,%
0.5
0.9
0.2
0.9
0.1
0.7
1.0
0NA
NA
*40mgevery
otherweek.
50mgweekly.
50mgtw
iceweekly.
5mgkgatweeks
0,2,6,thenevery
8weeks.
AE,adverseevent;NA
,notavailable;PASI,pso
riasisareaandse
verity
index.
2012 The AuthorJEADV 2012, 26 (Suppl. 2), 2129 Journal of the European Academy of Dermatology and Venereology 2012 European Academy of Dermatology and Venereology
Effective, sustainable biologic treatment of psoriasis 27
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