TABLE 1
Summary of results for reSURFACE 1 and reSURFACE 2 at week 12
Study details % achieving % achieving % achieving % achieving
PASI 75 PASI 100 PGA score 0 or 1 DLQI score 0 or 1
reSURFACE 1
Placebo (n = 154) 6 1 7 5
Tildrakizumab 100mg 64 * 14 58 * 42
(n = 309)
Tildrakizumab 200mg 62 * 14 59 * 44
(n = 308)
reSURFACE 2
Placebo (n = 156) 6 0 4 8
Tildrakizumab 100mg 61 ** 12 55 40
(n = 307)
Tildrakizumab 100mg 66 ** 12 59 ** 47 ***
(n = 314)
Etanercept 50mg (n = 313) 48 5 48 36
*p < 0.001 vs placebo, ** p < 0.05 vs etanercept, *** p < 0.05 vs etanercept)
and reSURFACE 2. The results from both trials were
published in the same paper 3 and are summarised in
Table 1. Both doses of tildrakizumab were given at
baseline and week 4 and every 12 weeks thereafter.
Doses of etanercept were given weekly. No more
than 40% of patients were allowed to have had
previous treatment with a biologic agent and mean
baseline PASI scores were approximately 20 for each
of the groups.
The co-primary endpoints in both trials were the
proportion achieving a PASI 75 and a PGA score or 0
(clear) or 1 (minimal) with a ≥2 score reduction from
baseline at week 12. Secondary endpoints included
the proportion achieving a PASI 100 at week 12 and
the proportion achieving a dermatology quality of
life index (DLQI) score of 0 or 1 (that is, indicating no
effect on quality of life).
The maximum efficacy in both studies was
reached between weeks 22 and 28.
As shown in Table 1, tildrakizumab was more
effective than etanercept. However, etanercept
targets tumour necrosis factor-a, an inflammatory
cytokine, which was found to be elevated in both
the blood and lesional skin and in recent years,
newer agents directed as IL-17 and IL-12/23 have
proved to be more efficacious, hence demonstrating
superior efficacy compared with etanercept.
Adverse events
The proportion of adverse events was similar in both
studies. For example, in reSURFACE 2, ≥1 adverse
event was experienced by 49% of patients assigned
to tildrakizumab 200mg vs 54% of those given
etanercept. The most common adverse event (for the
same two groups) was nasopharyngitis experienced
by 11 and 12% of patients respectively. The longer
term efficacy of the drug (up to 72 weeks) is not yet
published.
Place in therapy
Unfortunately, there is a lack of comparative headto-head
trials between the newer biologic agents, for
instances, a comparison of a specific IL-23 and IL-17
inhibitor. Nevertheless, a recent meta-analysis 4 has
shed some light on the different therapeutic options,
at least in the short-term. The analysis used data
from published clinical trials to compare the efficacy
and adverse effects of IL-17 inhibitors (ixekinumab,
secukinumab and brodalumab) and IL-23 inhibitors
(ustekinumab, guselkumab and tildrakizumab). The
results showed that the IL-17 inhibitor, ixekinumab
was the most efficacious (in terms of achieving
a PASI 75), followed by ustekinumab (IL-12/23
inhibitor), whereas the IL-23 inhibitor tildrakizumab
had fewest adverse effects.
These results suggest that the theoretical
advantage of blocking only the IL-23p19 subunit
(tildrakizumab) does not confer any clinical
advantages compared with blockage of the IL-
12/23p40 subunit (ustekinumab). Therefore
abrogating both the Th 1 and Th 17 inflammatory
pathways could represent a more effective
therapeutic option.
A limitation of this analysis was that it was
restricted to short-term use and longer-term data on
the relative efficacy and safety of the newer agents
is required for a fuller evaluation of the different
agents.
Conclusions
Tildrakizumab appears to be an effective drug that
could add to the therapeutic armamentarium of
clinicians when treating patients with moderate to
severe psoriasis.
References
1 Parirsi R et al. Global epidemiology of psoriasis: a systematic review
of incidence and prevalence. J Invest Dermatol 2013;133(2):377–85.
2 Papp K et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19
monoclonal antibody, improves psoriasis in a phase IIb randomised,
placebo-controlled trial. Br J Dermatol 2015;173:930–9.
3 Reich K et al. Tildrakizumab vs placebo or etanercept for chronic
plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two
randomised controlled, phase 3 trials. Lancet 2017;390:276–88.
4 Cui L et al. Efficacy and safety of biologics targeting IL-17 and
IL-23 in the treatment of moderate-to-severe plaque psoriasis:
A systematic review and meta-analysis of randomized controlled trials.
Int Immunopharmacol 2018;62:46–58.
Key points
• Psoriasis affects
between 2% and 4%
of the population in
Westernised countries.
• Psoriasis is now
recognised as an
immune-mediated
inflammatory disease.
• Current therapies for
those with moderate to
severe disease focus on
targeting cytokines, in
particular IL-17, IL12 and
IL-23.
• Tildrakizumab is a
monoclonal antibody that
specifically targets IL-23.
• Available clinical data
suggests that the drug is
effective but less so than
agents that specifically
target IL-17 or both IL-12
and IL-23.
hospitalpharmacyeurope.com | 2019 | Issue 91 | 31