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Psoriasis
Table 1: Safety and Efficacy of Biologics in Treating of use only approximately 46,000 patients have been exposed to it
Moderate to Severe Plaque Psoriasis
worldwide. Of these, around 4,000 patients have had more than
three years of exposure and their risk of PML is estimated at 0.1%.
Biologic No. of Achievement of PASI 75 One or More Adverse Event
In contrast, ustekinumab, infliximab, adalimumab and etanercept are
Studies (week 10–14) vs Placebo (week 10–30) vs Placebo
cytokine antagonists. There is longer and more widespread
RR NNT RR NNH
experience with the TNF-α antagonists across various indications,
Infliximab 4 17.40 2 1.18 9
and therefore much more clinical safety data are available.
(p<0.001)
Etanercept 4 11.73 3 Not increased 46
versus placebo
In the light of safety concerns, the PRIVATE recommendations may
Efalizumab 5 7.34 4 1.15 9
help to identify and eliminate the most serious side effects of biologic
(p<0.001)
treatment of psoriasis:
Alefacept 3 3.70 8 1.09 15
(p=0.03) • Prevent reactivation of latent infections: TB, hepatitis C and B
Meta-analysis of randomised controlled trials. RR = relative risk; NNH = number needed to
and HIV;
harm; NNT = number needed to treat.
• React immediately on atypical events or symptoms: interrupt
Source: Brimhall et al., 2008.
18
biologic therapy, examine patient thoroughly;
Table 2: Post-marketing Reports* of Granulomatous and • Inform patients about incipient symptoms of infections: biologics
Opportunistic Infections in Rheumatic Patients
may mitigate early signs of infection;
• Vaccinate for viral infections prior to and during biologic
Infliximab Etanercept p-value
treatment, if possible;
(n=197,000) (n=113,000)
• Assess patients for existing bacterial or viral infections and for
(n/100,000 (n/100,000
contraindications before treatment;
patients treated) patients treated)
• Treat newly arising infection resolutely; and
Coccidioidomycosis 11 (5,58) 1 (0.88) 0.013
Histoplasmosis 37 (18.78) 3 (2.65) <0.0001
• Expect unusual events.
Listeriosis 17 (8.63) 1 (0.88) 0.0006
Nocardiosis 7 (3.55) 1 (0.88) 0.090
Efficacy
Salmonellosis 0 (0) 2 (1.77) 0.031
Although infliximab has the greatest short-term efficacy of the
Tuberculosis 106 (53.81) 32 (28.32) <0.0001 biologic agents (see Table 2),
18
its efficacy decreases with long-term
*January 1998 to September 2002.
use: the EXPRESS I and II trials demonstrated a decrease of over 20%
Sources: Wallis et al., 2004;
20
Wallis et al., 2004;
21
Schaible, Clin Infect Dis, 2004;39:1255–6.
in response to infliximab from week 24 to week 50.
13
Two clinical trials
that inhibition of TNF may cause a greater risk of infection. Post- showed that efficacy is sustained with adalimumab for 60 weeks
marketing studies of granulomatous and opportunistic infections in when dosed every other week;
14,27
however, there may be a long-term
rheumatic patients indicated that patients receiving infliximab had a decrease in PASI 75 responders at week 60.
28
In the PHOENIX I trial, it
greater risk of granulomatous and opportunistic infection than those was shown that dosing with ustekinumab every 12 weeks maintained
receiving entanercept (see Table 2).
20,21
The rate and severity of efficacy for at least one year in most patients.
9
mycobacterial infection in general seems to be lower with etanercept
than with other TNF-α antagonists.
22
A UK register study showed that Several studies of varying length have demonstrated the long-term
the frequency of severe infections (those causing hospitalisations or efficacy of etanercept. In US/Canadian studies (etanercept safety
death) in RA were not increased with biological agents.
23
Two studies studies 115 and 117), extended exposure to 50mg of etanercept
involving treatment of psoriasis and PsA in patients with concomitant twice weekly resulted in AE and infection rates similar to those in
hepatitis C suggest that etanercept is a safe option in these cases.
24,25
patients receiving placebo. Improvements in PASI were observed for
up to 96 weeks of continuous etanercept therapy.
29
Data from the
Recently, significant safety problems have become apparent with the third period of the study, representing up to 144 weeks of exposure
use of efalizumab. Three confirmed cases of progressive multifocal to etanercept treatment, indicated that efficacy and safety were
leukoencephalopathy (PML) due to JC-polyoma virus infection sustained.
30
In safety study 216, 383 subjects from the previous
occurred in patients who had taken efalizumab for over three years. studies continued to 4.2 years of exposure of treatment with no
Moreover, efalizumab is associated with serious side effects, including further AEs noted.
31
Further long-term safety and efficacy data have
Guillain-Barré and Miller-Fisher syndromes, encephalitis, been demonstrated in paediatric psoriasis (211 patients in the US
encephalopathy, meningitis, sepsis and opportunistic infections. As and Canada; data up to 48 weeks).
32
The European CRYSTEL study
stated by the Committee for Medicinal Products for Human Use demonstrated sustained improvement in PASI 75 over 54 weeks
(CHMP) of the EMEA, there is insufficient evidence to suggest that the using a dosage of 50mg weekly.
33
benefits of efalizumab outweigh its risks. As a result, on 19 February
2009 the EMEA suspended marketing authorisation for efalizumab.
26
Improvement in Quality of Life
For all biologic agents, physical improvement is paralleled by
The suspension of efalizumab has raised safety fears about other improvements in quality of life. A correlation has been demonstrated
biologic agents. It is important to emphasise that direct comparisons between PASI ≥75 and improvement in health-related QoL (HRQoL)
cannot be made between safety aspects of efalizumab and other from two adalimumab trials.
34
A number of studies have shown that
biologics as their mechanisms of action differ: efalizumab the physical improvements demonstrated with etanercept treatment
suppresses a specific part of T-cell-mediated immunity. Clinical were accompanied by an improvement in depression and anxiety
experience with efalizumab is limited to psoriasis, and in four years symptoms and a significant improvement in patient QoL assessed by
4 EUROPEAN DERMATOLOGY
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