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Challenges in Managing Psoriasis – Opinion on Biologic Therapies
the Dermatology Life Quality Index (DLQI).
32,35
Similar observations psoriasis by 125% relative to the pre-treatment baseline within eight
have been made with infliximab.
36
weeks of discontinuation of therapy, and has been observed in
approximately 13% of patients.
49
Rebound on abrupt discontinuation
Reduction or Prevention of Co-morbidities of efalizumab has been reported in approximately 14% of patients
Numerous data show a correlation between psoriasis and increased and is avoided by transition to an alternative therapy.
5,11
Infliximab
incidence of cardiovascular risk factors.
37
Moreover, psoriasis is an has been used in rotational therapy after efalizumab rebound.
50
independent risk factor for myocardial infarction.
38
Any assessment of Limited data are available on discontinuation of infliximab and
psoriasis treatment should therefore include effect on co-morbidities. adalimumab, although no rebound effects have been reported. A
Studies on RA have demonstrated a link between anti-TNF use and a study involving withdrawal of patients from etanercept showed that
reduction in co-morbidities. Etanercept, infliximab and methotrexate upon drug withdrawal, the median time to disease relapse (loss of
were associated with a 0.55–0.71 reduction in mortality risks. The 50% of improvement) was 85 days. Furthermore, 25% of the
primary risk reduction appeared to be in cardiovascular disorders.
39
The responders did not relapse until at least 141 days. During the
use of a monoclonal TNF-α antibody, onercept, or etanercept in psoriasis withdrawal period, only one patient showed a deterioration of
patients demonstrated that TNF-α blockade may decrease the plasma psoriasis to levels worse than before treatment. No serious adverse
levels of cardiovascular risk factors such as C-reactive protein, events or hospitalisations related to worsening psoriasis occurred
lipoprotein A or homocysteine.
40,41
These observations suggest that during the withdrawal period.
51
A review of etanercept trials found
efficient control of inflammation by biologic agents might at the same no reported cases of rebound.
52
No rebound effects have been
time reduce cardiovascular morbidity and mortality in psoriasis patients. reported with ustekinumab and good responses have been gained
upon re-treatment; however, this is a relatively new treatment that
Treatment According to Needs lacks clinical data.
9
Many patients do not require continuous treatment with biologics as
they may experience long remissions after cessation of successful Treatment During Different Life Phases
treatment. Dermatologists often use an intermittent and/or rotational An important challenge to any therapy is the need for flexibility
paradigm when treating psoriasis, but limited data are available on the during different life phases, e.g. childhood, adolescence, family
safety and efficacy profiles of biologic agents when re-treating after planning, etc. Systemic therapies have been of limited value in these
drug withdrawal. The cases of PML in efalizumab treatment suggest areas because of low tolerability in children, cumulative adverse
that long-term immunosuppression may reactivate dormant viral effects and teratogenicity.
53
The treatment mode of infliximab
infections. Intermittent treatments may support the immune system to (intravenous [IV] infusion lasting for more than 120 minutes at weeks
keep or regain control over such infections. When treatment with zero, two and six, then every eight weeks) makes it less convenient
adalimumab for moderate to severe psoriasis is interrupted, patients for those with busy lifestyles than the other biologic agents, which
who have lost adequate response to initial treatment have a poorer are administered by subcutaneous injection at home once or twice
response when treatment is re-started.
42,43
Although re-treatment with weekly. Etanercept is currently the only biologic agent for which
infliximab in Crohn’s disease has been associated with a high rate of data are available for use in children. In a study of 211 children and
antibody development and shorter duration of response,
44
a study of adolescents (four to 17 years of age) with moderate to severe
infliximab therapy in severe psoriasis found that re-treatment infusions psoriasis, it significantly reduced disease severity up to 48 weeks.
32
with infliximab were well tolerated and led to further improvement in A major advantage of etanercept in terms of treatment flexibility is
64% of those on a 5mg/kg dose, although with a relatively high AE its short serum half-life (3.5 days, compared with 9.5 days for
rate.
45
However, due to a high risk of severe and potentially fatal infliximab, 16 days for adalimumab and 21 days for ustekinumab).
anaphylactic reactions, re-treatment with infliximab is now considered Consequently, if treatment interruption is necessary in cases such
as a contraindication by the manufacturer (infliximab product as infections, surgery, live vaccinations, pregnancy, etc., there is
information). No loss of efficacy has been observed on re-treatment rapid loss of activity.
54
with etanercept.
46
A phase III trial of etanercept in psoriasis involved
a 24-week treatment period followed by drug withdrawal and re- Efficacy in Psoriatic Arthritis
treatment following relapse. Comparison of PASI scores between week Only TNF-α antagonists are approved for both psoriasis and PsA,
55
12 of initial treatment and week 12 of re-treatment revealed that the although a pilot study suggests that ustekinumab is also effective.
56
overall effect of re-treatment with etanercept was similar to the initial
treatment effect. Moreover, 40% of patients re-treated for at least 12 Conclusions
weeks had improved PASI scores compared with those achieved over Biologic agents are expensive, but given the drawbacks of
their initial treatment. The AE, infection and antigenicity rates in the conventional therapies they have many advantages. At present, there
re-treatment period were lower than or similar to those seen on initial are limited studies detailing clinical use of some of these therapies, a
treatment.
47
A study evaluating the efficacy and safety of continuous lack of long-term safety data in psoriasis treatment and only one study
and paused etanercept regimens in psoriasis patients documented directly comparing different biologics.
57
However, great advances have
that both continuous and paused etanercept therapies improved been made in recent years and it seems likely that one or more of
Physician’s Global Assessment (PGA) and PASI scores and patient these agents will become a major therapeutic option. In this author’s
satisfaction rates; patients who paused and resumed active treatment opinion, while many biologic agents respond well to the different
generally recaptured response and experienced sustained benefit.
48
challenges presented, currently etanercept is the most balanced in
terms of meeting all requirements associated with treating psoriasis. It
Response to Treatment Discontinuation is suitable for the treatment of psoriasis in adults and children, is
A potential drawback of antipsoriatic therapies is rebound on effective in PsA, combines flexibility of treatment, long-term efficacy
discontinuation of treatment. Rebound is defined as worsening of and safety and holds the promise of reducing co-morbidities. n
EUROPEAN DERMATOLOGY 5
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